Neurosteroid-mediated regulation of brain innate immunity in HIV/AIDS: DHEA-S suppresses neurovirulence.

PubMed

Maingat, Ferdinand G; Polyak, Maria J; Paul, Amber M; Vivithanaporn, Pornpun; Noorbakhsh, Farshid; Ahboucha, Samir; Baker, Glen B; Pearson, Keir; Power, Christopher

2013-02-01

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during lentivirus infections, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid-mediated effects and lentivirus infection outcomes. Analyses of HIV-infected (HIV(+)) and uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV(+) macrophages exhibited suppressed enzyme expression without reduced cellular viability. HIV(+) human macrophages treated with sulfated dehydroepiandrosterone (DHEA-S) showed suppression of inflammatory gene (IL-1β, IL-6, TNF-α) expression. FIV-infected (FIV(+)) animals treated daily with 15 mg/kg body weight. DHEA-S treatment reduced inflammatory gene transcripts (IL-1β, TNF-α, CD3ε, GFAP) in brain compared to vehicle-(β-cyclodextrin)-treated FIV(+) animals similar to levels found in vehicle-treated FIV(-) animals. DHEA-S treatment also increased CD4(+) T-cell levels and prevented neurobehavioral deficits and neuronal loss among FIV(+) animals, compared to vehicle-treated FIV(+) animals. Reduced neuronal neurosteroid synthesis was evident in lentivirus infections, but treatment with DHEA-S limited neuroinflammation and prevented neurobehavioral deficits. Neurosteroid-derived therapies could be effective in the treatment of virus- or inflammation-mediated neurodegeneration.

Enhancement of Cognitive and Electrophysiological Measures of Hippocampal Functioning in Rats by a Low, But Not High, Dose of Dehydroepiandrosterone Sulfate (DHEAS)

PubMed Central

Diamond, David M.

2004-01-01

Dehydroepiandrosterone sulfate (DHEAS) is a steroid hornone that is synthesized, de novo, in the brain. Endogenous DHEAS levels correlate with the quality of mental and physical health, where the highest levels of DHEAS occur in healthy young adults and reduced levels of DHEAS are found with advanced age, disease, or extreme stress. DHEAS supplementation, therefore, may serve as a therapeutic agent against a broad range of maladies. This paper summarizes laboratory findings on dose-response relationships between DHEAS and cognitive and electrophysiological measures of hippocampal functioning. It was found that a low, but not a high, dose of DHEAS enhanced hippocampal primed burst potentiation (a physiological model of memory) as well as spatial (hippocampal-dependent) memory in rats. This complex dose-response function of DHEAS effects on the brain and memory may contribute toward the inconsistent findings that have been obtained by other investigators in studies on DHEAS administration in people. PMID:19330152

DHEA and cognitive function in the elderly.

PubMed

Maggio, Marcello; De Vita, Francesca; Fisichella, Alberto; Colizzi, Elena; Provenzano, Sandra; Lauretani, Fulvio; Luci, Michele; Ceresini, Graziano; Dall'Aglio, Elisabetta; Caffarra, Paolo; Valenti, Giorgio; Ceda, Gian Paolo

2015-01-01

The adrenal prohormone dehydroepiandrosterone (DHEA) and its sulphate conjugate (DHEAS) steadily decrease with age by 10% per decade reaching a nadir after the age of 80. Both DHEA and DHEAS (DHEA/S) exert many biological activities in different tissues and organs. In particular, DHEA and DHEAS are produced de novo in the brain, hence their classification as neurosteroids. In humans, the brain-to-plasma ratios for DHEA and DHEAS are 4-6.5 and 8.5, respectively, indicating a specific neuroendocrine role for these hormones. DHEA/S stimulates neurite growth, neurogenesis and neuronal survival, apoptosis, catecholamine synthesis and secretion. Together with antioxidant, anti-inflammatory and anti-glucocorticoid properties, it has been hypothesized a neuroprotective effect for DHEA/S. We conducted an accurate research of the literature using PubMed. In the period of time between 1994 and 2013, we selected the observational human studies testing the relationship between DHEA/S and cognitive function in both sexes. The studies are presented according to the cross-sectional and longitudinal design and to the positive or neutral effects on different domains of cognitive function. We also analysed the Clinical Trials, available in the literature, having cognitive domains as the main or secondary outcome. Although the cross-sectional evidence of a positive association between DHEA/S and cognitive function, longitudinal studies and RCTs using DHEA oral treatment (50mg/day) in normal or demented adult-older subjects, have produced conflicting and inconsistent results. In summary, the current data do not provide clear evidence for the usefulness of DHEA treatment to improve cognitive function in adult-older subjects. This article is part of a Special Issue entitled 'Essential role of DHEA'. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effort-reward imbalance work-stress model and daytime salivary cortisol and dehydroepiandrosterone (DHEA) among Japanese women.

PubMed

Ota, Atsuhiko; Mase, Junji; Howteerakul, Nopporn; Rajatanun, Thitipat; Suwannapong, Nawarat; Yatsuya, Hiroshi; Ono, Yuichiro

2014-09-17

We examined the influence of work-related effort-reward imbalance and overcommitment to work (OC), as derived from Siegrist's Effort-Reward Imbalance (ERI) model, on the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that, among healthy workers, both cortisol and dehydroepiandrosterone (DHEA) secretion would be increased by effort-reward imbalance and OC and, as a result, cortisol-to-DHEA ratio (C/D ratio) would not differ by effort-reward imbalance or OC. The subjects were 115 healthy female nursery school teachers. Salivary cortisol, DHEA, and C/D ratio were used as indexes of HPA activity. Mixed-model analyses of variance revealed that neither the interaction between the ERI model indicators (i.e., effort, reward, effort-to-reward ratio, and OC) and the series of measurement times (9:00, 12:00, and 15:00) nor the main effect of the ERI model indicators was significant for daytime salivary cortisol, DHEA, or C/D ratio. Multiple linear regression analyses indicated that none of the ERI model indicators was significantly associated with area under the curve of daytime salivary cortisol, DHEA, or C/D ratio. We found that effort, reward, effort-reward imbalance, and OC had little influence on daytime variation patterns, levels, or amounts of salivary HPA-axis-related hormones. Thus, our hypotheses were not supported.

No Difference in Mood and Quality of Life in DHEA-S Deficient Adults with Addison's Disease vs. Type 2 Diabetes Patients with Normal DHEA-S Levels: Implications for Management of These Conditions.

PubMed

Heald, Adrian H; Walther, Andreas; Davis, Julian R E; Moreno, Gabriela Y C; Kane, John; Livingston, Mark; Fowler, Helen L

2017-01-01

Patients with Addison's disease have relatively high rates of depression and anxiety symptoms compared with population-based reference samples. Addison's disease results in deficiency of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). There is considerable debate about the specific effects of DHEA deficiency on energy level and mood. We measured emotional well-being in 16 patients with Addison's disease and a group of 16 hospital attendees with type 2 diabetes. Participants completed the General Health Questionnaire-28 (GHQ-28), the Hospital Anxiety and Depression Scale (HADS), the World Health Organization's quality of life assessment (WHOQOL-BREF) and the Holmes-Rahe life event scale. DHEA-S was low in Addison's patients (Addison's men: 0.5 ± 0.1 μmol/l [normal range: 2.1-10.8] compared with diabetes men: 3.2 ± 1.2 μmol/l; Addison's women: 0.4 ± 0.01 μmol/l [normal range: 1.0-11.5] compared with diabetes women: 2.2 ± 0.71 μmol/l). Testosterone levels were similar in both groups studied. There were no differences in emotional well-being and quality of life (QOL) between patients with Addison's disease and Type 2 Diabetes Mellitus as measured by GHQ-28 (Addison's: 22.4 ± 2.6, Diabetes: 19.6 ± 2.7), HADS Depression (Addison's: 5.4 ± 0.9, Diabetes: 4.5 ± 1.4), HADS Anxiety and WHOQOL-BREF. There were no gender differences in affective symptomatology within the Addison's group. Life event scores were above average in both groups (Addison's: 195 ± 39.6, Diabetes: 131 ± 43.8), but not significant for difference between groups as was GHQ-28 total score. Both groups scored highly on the GHQ-28 and the life event scale, indicative of poorer health perceptions than the general population. This could be due to the chronicity of both disorders. We have not identified any specific effects of DHEA-S deficiency on mood or QOL.

No Difference in Mood and Quality of Life in DHEA-S Deficient Adults with Addison’s Disease vs. Type 2 Diabetes Patients with Normal DHEA-S Levels: Implications for Management of These Conditions

PubMed Central

Heald, Adrian H.; Walther, Andreas; Davis, Julian R. E.; Moreno, Gabriela Y. C.; Kane, John; Livingston, Mark; Fowler, Helen L.

2017-01-01

Patients with Addison’s disease have relatively high rates of depression and anxiety symptoms compared with population-based reference samples. Addison’s disease results in deficiency of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). There is considerable debate about the specific effects of DHEA deficiency on energy level and mood. We measured emotional well-being in 16 patients with Addison’s disease and a group of 16 hospital attendees with type 2 diabetes. Participants completed the General Health Questionnaire-28 (GHQ-28), the Hospital Anxiety and Depression Scale (HADS), the World Health Organization’s quality of life assessment (WHOQOL-BREF) and the Holmes–Rahe life event scale. DHEA-S was low in Addison’s patients (Addison’s men: 0.5 ± 0.1 μmol/l [normal range: 2.1–10.8] compared with diabetes men: 3.2 ± 1.2 μmol/l; Addison’s women: 0.4 ± 0.01 μmol/l [normal range: 1.0–11.5] compared with diabetes women: 2.2 ± 0.71 μmol/l). Testosterone levels were similar in both groups studied. There were no differences in emotional well-being and quality of life (QOL) between patients with Addison’s disease and Type 2 Diabetes Mellitus as measured by GHQ-28 (Addison’s: 22.4 ± 2.6, Diabetes: 19.6 ± 2.7), HADS Depression (Addison’s: 5.4 ± 0.9, Diabetes: 4.5 ± 1.4), HADS Anxiety and WHOQOL-BREF. There were no gender differences in affective symptomatology within the Addison’s group. Life event scores were above average in both groups (Addison’s: 195 ± 39.6, Diabetes: 131 ± 43.8), but not significant for difference between groups as was GHQ-28 total score. Both groups scored highly on the GHQ-28 and the life event scale, indicative of poorer health perceptions than the general population. This could be due to the chronicity of both disorders. We have not identified any specific effects of DHEA-S deficiency on mood or QOL. PMID:28553251

Monitoring dehydroepiandrosterone (DHEA) in the urine of Thoroughbred geldings for doping control purposes.

PubMed

Viljanto, Marjaana; Hincks, Pamela; Hillyer, Lynn; Cawley, Adam; Suann, Craig; Noble, Glenys; Walker, Christopher J; Parkin, Mark C; Kicman, Andrew T; Scarth, James

2018-05-24

The use of testosterone and its pro-drugs, such as DHEA, is currently regulated in horseracing by the application of international testosterone thresholds. However, additional steroidomic approaches, such as steroid ratios, to distinguish overall adrenal stimulation from drug administrations and an equine biological passport for longitudinal steroid profiling of individual animals could be advantageous in equine doping testing. Thus, DHEA concentrations and related ratios (testosterone (T) to DHEA and DHEA to epitestosterone (E)) were assessed in the reference population by quantitative analysis of 200 post-race gelding urine samples using liquid chromatography tandem mass spectrometry. DHEA concentrations ranged between 0.9 and 136.6 ng/mL (mean 12.8 ng/mL), T:DHEA ratios between 0.06 and 1.85 (mean 0.43) and DHEA:E ratios between 0.21 and 13.56 (mean 2.20). Based on the reference population statistical upper limits of 5.4 for T:DHEA ratio and 48.1 for DHEA:E ratio are proposed with a risk of 1 in 10,000 for a normal outlier exceeding the value. Analysis of post-administration urine samples collected following administrations of DHEA, EquiBolic&® (a mix of DHEA and pregnenolone) and testosterone propionate to geldings showed that the upper limit for T:DHEA ratio was exceeded following testosterone propionate administration and DHEA:E ratio following DHEA administrations and thus these ratios could be used as additional biomarkers when determining the cause of an atypical testosterone concentration. Additionally, DHEA concentrations and ratios can be used as a starting point to establish reference ranges for an equine biological passport. This article is protected by copyright. All rights reserved.

The Effort-reward Imbalance work-stress model and daytime salivary cortisol and dehydroepiandrosterone (DHEA) among Japanese women

PubMed Central

Ota, Atsuhiko; Mase, Junji; Howteerakul, Nopporn; Rajatanun, Thitipat; Suwannapong, Nawarat; Yatsuya, Hiroshi; Ono, Yuichiro

2014-01-01

We examined the influence of work-related effort–reward imbalance and overcommitment to work (OC), as derived from Siegrist's Effort–Reward Imbalance (ERI) model, on the hypothalamic–pituitary–adrenocortical (HPA) axis. We hypothesized that, among healthy workers, both cortisol and dehydroepiandrosterone (DHEA) secretion would be increased by effort–reward imbalance and OC and, as a result, cortisol-to-DHEA ratio (C/D ratio) would not differ by effort–reward imbalance or OC. The subjects were 115 healthy female nursery school teachers. Salivary cortisol, DHEA, and C/D ratio were used as indexes of HPA activity. Mixed-model analyses of variance revealed that neither the interaction between the ERI model indicators (i.e., effort, reward, effort-to-reward ratio, and OC) and the series of measurement times (9:00, 12:00, and 15:00) nor the main effect of the ERI model indicators was significant for daytime salivary cortisol, DHEA, or C/D ratio. Multiple linear regression analyses indicated that none of the ERI model indicators was significantly associated with area under the curve of daytime salivary cortisol, DHEA, or C/D ratio. We found that effort, reward, effort–reward imbalance, and OC had little influence on daytime variation patterns, levels, or amounts of salivary HPA-axis-related hormones. Thus, our hypotheses were not supported. PMID:25228138

Human DHEA sulfation requires direct interaction between PAPS synthase 2 and DHEA sulfotransferase SULT2A1.

PubMed

Mueller, Jonathan W; Idkowiak, Jan; Gesteira, Tarsis F; Vallet, Cecilia; Hardman, Rebecca; van den Boom, Johannes; Dhir, Vivek; Knauer, Shirley K; Rosta, Edina; Arlt, Wiebke

2018-06-22

The high-energy sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS), generated by human PAPS synthase isoforms PAPSS1 and PAPSS2, is required for all human sulfation pathways. Sulfotransferase SULT2A1 uses PAPS for sulfation of the androgen precursor dehydroepiandrosterone (DHEA), thereby reducing downstream activation of DHEA to active androgens. Human PAPSS2 mutations manifest with undetectable DHEA sulfate, androgen excess, and metabolic disease, suggesting that ubiquitous PAPSS1 cannot compensate for deficient PAPSS2 in supporting DHEA sulfation. In knockdown studies in human adrenocortical NCI-H295R1 cells, we found that PAPSS2, but not PAPSS1, is required for efficient DHEA sulfation. Specific APS kinase activity, the rate-limiting step in PAPS biosynthesis, did not differ between PAPSS1 and PAPSS2. Co-expression of cytoplasmic SULT2A1 with a cytoplasmic PAPSS2 variant supported DHEA sulfation more efficiently than co-expression with nuclear PAPSS2 or nuclear/cytosolic PAPSS1. Proximity ligation assays revealed protein-protein interactions between SULT2A1 and PAPSS2 and, to a lesser extent, PAPSS1. Molecular docking studies showed a putative binding site for SULT2A1 within the PAPSS2 APS kinase domain. Energy-dependent scoring of docking solutions identified the interaction as specific for the PAPSS2 and SULT2A1 isoforms. These findings elucidate the mechanistic basis for the selective requirement for PAPSS2 in human DHEA sulfation. © 2018 Mueller et al.

Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS.

PubMed

Vieira-Marques, Claudia; Arbo, Bruno Dutra; Cozer, Aline Gonçalves; Hoefel, Ana Lúcia; Cecconello, Ana Lúcia; Zanini, Priscila; Niches, Gabriela; Kucharski, Luiz Carlos; Ribeiro, Maria Flávia M

2017-07-01

DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases. Copyright © 2016. Published by Elsevier Ltd.

Different DHEA-S Levels and Response Patterns in Individuals with Chronic Neck Pain, Compared with a Pain Free Group-a Pilot Study.

PubMed

Grimby-Ekman, A; Ghafouri, B; Sandén, H; Larsson, B; Gerdle, B

2017-05-01

To test, in this pilot study, whether DHEA-S (Dehydroepiandrosterone, sulfated form) plasma levels are lower among persons with chronic neck pain, compared to control persons, and to investigate the DHEA-S response after a physical exercise. Included were 12 persons with chronic neck pain and eight controls without present pain, all 18 and 65 years of age. Exclusion criteria for both groups were articular diseases or tendinosis, fibromyalgia, systemic inflammatory and neuromuscular diseases, pain conditions due to trauma, or severe psychiatric diseases. The participants arm-cycled on an ergometer for 30 minutes. Blood samples were taken before, 60 minutes, and 150 minutes after this standardized physical exercise. The estimated plasma DHEA-S levels at baseline were 2.0 µmol/L (95% confidence interval [CI] 1.00; 4.01) in the pain group and 4.1 µmol/L (95% CI2.0; 8.6) in the control group, adjusted for sex, age, body mass index (BMI), and Shirom-Melamed Burnout Questionnaire (SMBQ), with a ratio of 0.48 ( P  = 0.094). In this pilot study, the plasma DHEA-S levels appeared to be lower among the persons with chronic neck pain, compared with the control group. It was indicated that DHEA-S decreased during the physical exercise in the control group, and either increased or was unaffected in the chronic pain group. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Cortisol and DHEA in development and psychopathology.

PubMed

Kamin, Hayley S; Kertes, Darlene A

2017-03-01

Dehydroepiandrosterone (DHEA) and cortisol are the most abundant hormones of the human fetal and adult adrenals released as end products of a tightly coordinated endocrine response to stress. Together, they mediate short- and long-term stress responses and enable physiological and behavioral adjustments necessary for maintaining homeostasis. Detrimental effects of chronic or repeated elevations in cortisol on behavioral and emotional health are well documented. Evidence for actions of DHEA that offset or oppose those of cortisol has stimulated interest in examining their levels as a ratio, as an alternate index of adrenocortical activity and the net effects of cortisol. Such research necessitates a thorough understanding of the co-actions of these hormones on physiological functioning and in association with developmental outcomes. This review addresses the state of the science in understanding the role of DHEA, cortisol, and their ratio in typical development and developmental psychopathology. A rationale for studying DHEA and cortisol in concert is supported by physiological data on the coordinated synthesis and release of these hormones in the adrenal and by their opposing physiological actions. We then present evidence that researching cortisol and DHEA necessitates a developmental perspective. Age-related changes in DHEA and cortisol are described from the perinatal period through adolescence, along with observed associations of these hormones with developmental psychopathology. Along the way, we identify several major knowledge gaps in the role of DHEA in modulating cortisol in typical development and developmental psychopathology with implications for future research. Copyright © 2016 Elsevier Inc. All rights reserved.

DHEA, DHEAS and PCOS.

PubMed

Goodarzi, Mark O; Carmina, Enrico; Azziz, Ricardo

2015-01-01

Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production, primarily using DHEAS as a marker of APA in general and more specifically DHEA, synthesis. The role of APA excess in determining or causing PCOS is unclear, although observations in patients with inherited APA excess (e.g., patients with 21-hydroxylase deficient congenital classic or non-classic adrenal hyperplasia) demonstrate that APA excess can result in a PCOS-like phenotype. Inherited defects of the enzymes responsible for steroid biosynthesis, or defects in cortisol metabolism, account for only a very small fraction of women suffering from hyperandrogenism or APA excess. Rather, women with PCOS and APA excess appear to have a generalized exaggeration in adrenal steroidogenesis in response to ACTH stimulation, although they do not have an overt hypothalamic-pituitary-adrenal axis dysfunction. In general, extra-adrenal factors, including obesity, insulin and glucose levels, and ovarian secretions, play a limited role in the increased APA production observed in PCOS. Substantial heritabilities of APAs, particularly DHEAS, have been found in the general population and in women with PCOS; however, the handful of SNPs discovered to date account only for a small portion of the inheritance of these traits. Paradoxically, and as in men, elevated levels of DHEAS appear to be protective against cardiovascular risk in women, although the role of DHEAS in modulating this risk in women with PCOS remains unknown. In summary, the exact cause of APA excess in PCOS remains unclear, although it may reflect a generalized and inherited exaggeration in androgen biosynthesis of an inherited nature. Copyright © 2014 Elsevier Ltd. All rights reserved.

Faulty serotonin--DHEA interactions in autism: results of the 5-hydroxytryptophan challenge test.

PubMed

Croonenberghs, Jan; Spaas, Kristien; Wauters, Annick; Verkerk, Robert; Scharpe, Simon; Deboutte, Dirk; Maes, Michael

2008-06-01

Autism is accompanied by peripheral and central disorders in the metabolism of serotonin (5-HT). The present study examines plasma dehydroepiandrosterone-sulphate (DHEA-S) and the cortisol/DHEA-S ratio following administration of L-5-hydroxytryptophan (5-HTP), the direct precursor of 5-HT, to autistic patients. Plasma DHEA-S levels were determined both before and after administration of 5-HTP or placebo, on two consecutive days in a single blind order in 18 male autistic patients and 22 matched healthy controls. The 5-HTP-induced DHEA-S responses were significantly higher in autistic patients than in controls. In baseline conditions, the cortisol/DHEA-S ratio was significantly higher in autistic patients than in controls. The results suggest that autism is accompanied by a major disequilibrium in the serotonergic system. The increased Cortisol (neurotoxic) versus DHEA-S (neuroprotective) ratio suggests that an increased neurotoxic potential occurs in autism. It is concluded that a disequilibrium in the peripheral and central turnover of serotonin and an increased neurotoxic capacity by glucocorticoids are important pathways in autism.

Dehydroepiandrosterone (DHEA) metabolism in Saccharomyces cerevisiae expressing mammalian steroid hydroxylase CYP7B: Ayr1p and Fox2p display 17beta-hydroxysteroid dehydrogenase activity.

PubMed

Vico, Pedro; Cauet, Gilles; Rose, Ken; Lathe, Richard; Degryse, Eric

2002-07-01

We have engineered recombinant yeast to perform stereospecific hydroxylation of dehydroepiandrosterone (DHEA). This mammalian pro-hormone promotes brain and immune function; hydroxylation at the 7alpha position by P450 CYP7B is the major pathway of metabolic activation. We have sought to activate DHEA via yeast expression of rat CYP7B enzyme. Saccharomyces cerevisiae was found to metabolize DHEA by 3beta-acetylation; this was abolished by mutation at atf2. DHEA was also toxic, blocking tryptophan (trp) uptake: prototrophic strains were DHEA-resistant. In TRP(+) atf2 strains DHEA was then converted to androstene-3beta,17beta-diol (A/enediol) by an endogenous 17beta-hydroxysteroid dehydrogenase (17betaHSD). Seven yeast polypeptides similar to human 17betaHSDs were identified: when expressed in yeast, only AYR1 (1-acyl dihydroxyacetone phosphate reductase) increased A/enediol accumulation, while the hydroxyacyl-CoA dehydrogenase Fox2p, highly homologous to human 17betaHSD4, oxidized A/enediol to DHEA. The presence of endogenous yeast enzymes metabolizing steroids may relate to fungal pathogenesis. Disruption of AYR1 eliminated reductive 17betaHSD activity, and expression of CYP7B on the combination background (atf2, ayr1, TRP(+)) permitted efficient (>98%) bioconversion of DHEA to 7alpha-hydroxyDHEA, a product of potential medical utility. Copyright 2002 John Wiley & Sons, Ltd.

DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli

PubMed Central

Sripada, Rebecca K; Marx, Christine E; King, Anthony P; Rajaram, Nirmala; Garfinkel, Sarah N; Abelson, James L; Liberzon, Israel

2013-01-01

Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA's antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA's impact on emotion modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3T fMRI while performing the shifted-attention emotion appraisal task (SEAT), a test of emotional processing and regulation. Compared with placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA reduced memory accuracy for emotional stimuli, and also reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions and invite further investigation into the brain basis of neurosteroid emotion regulatory effects. PMID:23552182

The effects of DHEA, 3beta-hydroxy-5alpha-androstane-6,17-dione, and 7-amino-DHEA analogues on short term and long term memory in the mouse.

PubMed

Bazin, Marc-Antoine; El Kihel, Laïla; Boulouard, Michel; Bouët, Valentine; Rault, Sylvain

2009-11-01

Neurosteroids have been reported to modulate memory processes in rodents. Three analogues of dehydroepiandrosterone (DHEA), two of them previously described (7beta-aminoDHEA and 7beta-amino-17-ethylenedioxy-DHEA), and a new one (3beta-hydroxy-5alpha-androstane-6,17-dione) were synthesized, and their effects were evaluated on memory. This study examined their effects on long term and short term memory in male (6 weeks old) NMRI mice in comparison with the reference drug. Long term memory was assessed using the passive avoidance task and short term memory (spatial working memory) using the spontaneous alternation task in a Y maze. Moreover, the effects of DHEA and its analogues on spontaneous locomotion were measured. In all tests, DHEA and analogues were injected at three equimolar doses (0.300-1.350-6.075 microM/kg). DHEA and its three analogues administered immediately post-training at the highest doses (6.075 microM/kg, s.c.) improved retention in passive avoidance test. Without effect per se in the spatial working memory task, the four compounds failed to reverse scopolamine (1mg/kg, i.p.)-induced deficit in spontaneous alternation. These data suggested an action of DHEA and analogues in consolidation of long term memory particularly when emotional components are implied. Moreover, data indicated that pharmacological modulation of DHEA as performed in this study provides derivatives giving the same mnemonic profile than reference molecule.

DHEA-sulfate test

MedlinePlus

... women, DHEA contributes to normal libido and sexual satisfaction. DHEA may also have effects on the immune ... are concerned about low libido or decreased sexual satisfaction. The test is also done in children who ...

PTSD and depressive symptoms are linked to DHEAS via personality.

PubMed

Savic, Danka; Knezevic, Goran; Matic, Gordana; Damjanovic, Svetozar

2018-06-01

Research results on dehydroepiandrosterone sulfate ester (DHEAS) in post-traumatic stress disorder (PTSD) are inconsistent. We hypothesized that personality traits could be the confounders of DHEAS levels and disease symptoms, which could in part explain the discrepancy in findings. This study was a part of a broader project in which simultaneous psychological and biological investigations were carried out in hospital conditions. 380 male subjects were categorized in four groups: A) current PTSD (n = 132), B) lifetime PTSD (n = 66), C) trauma controls (n = 101), and D) healthy controls (n = 81), matched by age. The level of DHEAS is significantly lower in the current PTSD group than in trauma controls. All groups significantly differ in personality traits Disintegration and Neuroticism (current PTSD group having the highest scores). DHEAS is related to both PTSD and depressive symptoms; however, Structural Equation Model (SEM) shows that the relations are indirect, realized via their confounder - personality trait Disintegration. According to our project results, DHEAS is the second putative biomarker for trauma-related disorders that fails to fulfil this expectation. It appears to be more directly related to personality than to the disease symptoms (the first one being basal cortisol). Our data promote personality as a biologically based construct with seemingly important role in understanding the mental health status. Copyright © 2018 Elsevier Ltd. All rights reserved.

DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA's antidepressant action.

PubMed

Ben Dor, Rivka; Marx, Christine E; Shampine, Lawrence J; Rubinow, David R; Schmidt, Peter J

2015-09-01

Alterations in neurosteroid secretion have been implicated in the efficacy of antidepressants. In a previous study, the adrenal androgen DHEA, a precursor of the neurosteroid androsterone, produced antidepressant and libido-enhancing effects in patients with midlife depression. To investigate the mechanisms underlying DHEA's behavioral effects in this same patient group, we examined plasma levels of four additional neurosteroids implicated in the regulation of affective behavior. Blood samples were assayed for neurosteroids in men (n = 13) and women (n = 10) with midlife depression who previously participated in a crossover study in which DHEA and placebo were administered for 6 weeks each. Depression severity was measured by the Center for Epidemiologic Studies Depression Scale (CES-D). Plasma levels of androsterone (ADT), allopregnanolone, pregnanolone, and pregnenolone were measured by GC-MS at baseline and week 6 of each treatment phase. Data were analyzed with repeated measures analysis of variance (ANOVA-R) and Bonferroni t tests. ADT levels (but not allopregnanolone, pregnanolone, and pregnenolone) increased after DHEA but not after placebo (F 2,42 = 3.3, p < 0.05). Post-DHEA ADT levels were higher in women than men [t 63 = 2.9, p < 0.05]. However, in both men and women who met criteria for clinical response on the CES-D, baseline ADT levels significantly increased post-DHEA, and the magnitude of the ADT increase post-DHEA treatment was similar in men and women. Consequently, it was the non-responders who accounted for the sex difference in post-DHEA plasma ADT levels, a difference that was driven by values in two women (the only female non-responders). The small sample size notwithstanding, these data emphasize the potential behavioral relevance of ADT in humans, which may include contribution to the antidepressant effects of DHEA.

Changes in DHEA-s levels during the first year of treatment in patients with clinical burnout are related to health development.

PubMed

Lennartsson, Anna-Karin; Theorell, Töres; Kushnir, Mark M; Jonsdottir, Ingibjörg H

2016-10-01

The regenerative hormone DHEA-S was measured in 122 patients with clinical burnout during their first year of treatment. Relations between change of DHEA-S levels and development in health were investigated. About half of the patients exhibited increased DHEA-S levels during the year, while the other half exhibited decreased levels. There was no difference in burnout symptoms or associated health status at baseline between subsequent DHEA-S increasing and DHEA-S decreasing groups. Greater reduction in the burnout symptoms was observed in patients in who DHEA-S levels increased during the year, than in the patients in who DHEA-S levels decreased. Relative change of DHEA-S and direction of the change during the year both predicted burnout symptoms at the end of the year. In addition, patients with increased DHEA-S levels had better self-rated health, vitality and well-being. Our data suggest that changes in DHEA-S are associated with prognosis for the outcome in burnout patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults.

PubMed

Søeborg, Tue; Frederiksen, Hanne; Mouritsen, Annette; Johannsen, Trine Holm; Main, Katharina Maria; Jørgensen, Niels; Petersen, Jørgen Holm; Andersson, Anna-Maria; Juul, Anders

2014-11-01

The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798 serum samples from healthy children, adolescents and young adults was evaluated. Samples were analyzed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analyzed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes and generally higher in males than in females except for Adione. The pubertal rise in T in males was more pronounced compared to females, reflecting contribution from the testes. Ratios between steroid metabolites varied and depended on sex and age. All ratios were lower during infancy compared to later in life. Use of oral contraceptives significantly lowered serum concentrations of all steroid metabolites, fT, FAI, the 17-OHP/Adione, the Adione/T and the DHEA/Adione ratios, but not the DHEA/DHEAS ratio. We provide reference ranges for DHEA, DHEAS, 17-OHP, Adione, T, fT, FAI and selected ratios in relation to sex, age and pubertal development. Use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with disorders of sex development. Copyright © 2014 Elsevier B.V. All rights reserved.

Dehydroepiandrosterone and dehydroepiandrosterone sulfate: anabolic, neuroprotective, and neuroexcitatory properties in military men.

PubMed

Taylor, Marcus K

2013-01-01

Evidence links dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) to crucial military health issues, including operational stress, resilience, and traumatic brain injury. This study evaluated the anabolic, neuroprotective, and neuroexcitatory properties of DHEA(S) in healthy military men. A salivary sample was obtained from 42 men and assayed for DHEA(S), testosterone, nerve growth factor (NGF; which supports nerve cell proliferation), and salivary alpha amylase (sAA; a proxy of sympathetic nervous system function). Separate regression analyses were conducted with DHEA and DHEAS as independent variables, and testosterone, NGF, and sAA as dependent variables, respectively. The models explained 23.4% of variance in testosterone (p < 0.01), 17.2% of variance in NGF (p < 0.01), and 7.4% of variance in sAA (p = 0.09). Standardized beta coefficients revealed that DHEA independently influenced testosterone (beta = 0.40, p < 0.01), whereas DHEAS independently influenced NGF (beta = 0.48, p < 0.01) and sAA (beta = 0.36, p < 0.05). DHEA demonstrated anabolic properties, whereas DHEAS demonstrated neuroprotective and neuroexcitatory properties in military men. This area of study has broad implications for stress inoculation, traumatic brain injury rehabilitation, and regenerative medicine in military personnel.

Effects of DHEA (Dehydroepiandrosterone) on Host Virus Interactions

DTIC Science & Technology

1988-06-28

virulence of an RNA and DNA virus that are lethal by widely different mechanisms. I 3 I .ATERIAILS AND TODS Viruses and tissue culture procedures Two...intermediary in testosterone and estradiol metabolism [Tyrell, 1983], can prevent mortality normally seen with two distinct classes of viruses . We are...resistance and/or the immune system rather than upon the viruses _er see. This supposition is supported by the observations that [1] DHEA failed to influence

Control of the immune response by DHEA and its metabolites.

PubMed

Loria, R M; Padgett, D A

1998-06-01

The 17 keto steroid, Dehydroepiandrosterone (5-androsten-3 beta-17-one, DHEA) has been shown to protect mice from a variety of lethal infections. This includes, but is not limited to, infection with viruses (herpesvirus type 2, coxsackievirus B4-CVB4),bacteria (Enterococcus faecalis, Pseudomonas aeruginosa), and a parasite (Cryptosporidium parvum). We have reported that androstenediol (5-androsten-3 beta-17 beta-diol, beta AED), which is derived from DHEA, is at least 100x more effective in up-regulating systemic resistance against CVB4-infection than its precursor. Furthermore, androstenetriol (5-androstene-3 beta-7 beta-17 beta-triol beta AET) which is formed by 7 beta hydroxylation of beta AED, was more effective against CVB4-infection than its precursor beta AED. Neither steroid however has shown any significant direct antiviral effects. The in-vitro influences of DHEA, beta AED, and beta AET on a mitogen-induced mixed splenocyte proliferation assay were determined. The results showed that DHEA suppressed the proliferation of concanavalin A (Con A) or lipopolysaccharide (LPS) activated cultures in a dose dependent manner. beta AED had little influence on the activation response. However, beta AET potentiated the response to both mitogens significantly above control. The regulation of interleukin-2 and interleukin-3 secretion from Con A-activated lymphocytes was analogous to these observations. These functions were suppressed by DHEA, unaffected by beta AED, and potently increased by beta AET. Moreover, the classic immuno-suppressive effects of hydro-cortisone on Con A-induced lymphocyte proliferation, as well as IL-2 and IL-3 production were unaffected by co-cultured with DHEA and only minimally counteracted by beta AED. In contrast, beta AET significantly counteracted the effect of hydrocortisone when co-cultured together. These results show that while in-vivo, DHEA, beta AED, and beta AET each function in a similar manner. In-vitro, their effects are

Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats

PubMed Central

Hulin, Mary W.; Lawrence, Michelle N.; Amato, Russell J.; Weed, Peter F.; Winsauer, Peter J.

2015-01-01

The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and Drug Administration (FDA)-approved pharmacotherapies, naltrexone and acamprosate. Experiment 1 assessed the effects of different doses of DHEA, pregnanolone, naltrexone, and acamprosate on both ethanol- and food-maintained responding under a multiple fixed-ratio (FR)-10 FR-20 schedule, respectively. Experiment 2 assessed the effects of different mean intervals of food presentation on responding for ethanol under an FR-10 variable-interval (VI) schedule, whereas Experiment 3 assessed the effects of a single dose of each drug under a FR-10 VI-80 schedule. In Experiment 1, all four drugs dose-dependently decreased response rate for both food and ethanol, although differences in the rate-decreasing effects were apparent among the drugs. DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding, whereas the reverse was true for naltrexone. Acamprosate decreased responding for both reinforcers with equal potency. In Experiment 2, different mean intervals of food presentation significantly affected the number of food reinforcers obtained per session; however, changes in the number of food reinforcements did not significantly affect responding for ethanol. Under the FR-10 VI-80 schedule in Experiment 3, only naltrexone significantly decreased both the dose of alcohol presented and blood ethanol concentration (BEC). Acamprosate and pregnanolone had no significant effects on any of the dependent measures, whereas DHEA significantly decreased BEC, but did not significantly decrease response rate or the dose presented. In summary, DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding under a multiple FR-10 FR-20 schedule, and were more selective for decreasing ethanol self-administration than either naltrexone or

Effect of DHEAS on skeletal muscle over the life span: the InCHIANTI study.

PubMed

Valenti, Giorgio; Denti, Licia; Maggio, Marcello; Ceda, GianPaolo; Volpato, Stefano; Bandinelli, Stefania; Ceresini, Graziano; Cappola, Anne; Guralnik, Jack M; Ferrucci, Luigi

2004-05-01

It has been suggested that the reduced production of dehydroepiandrosterone sulfate (DHEAS) may be partially responsible for the decline of muscle strength and mass that often occurs with aging. However, this hypothesis has been only tested in small series of normal volunteers, with little consideration for potential confounders. Using data from a representative sample of 558 men (20-95 years) we tested the hypothesis that circulating DHEAS is independently associated with muscle strength and mass. Data are from InCHIANTI, an epidemiological study conducted in the Chianti geographic area (Tuscany, Italy). DHEAS serum levels were related to lower extremity muscle strength assessed by hand-held dynamometry and calf muscle area estimated from quantitative computerized tomography. Confounders included age, anthropometrics, physical activity, smoking, energy and alcohol intake, albumin, lipids, interleukin-6, comorbidity, depressive symptoms, and disability in activities of daily living. In fully adjusted models predicting lower extremity muscle strength and calf muscle area, we found significant age*log DHEAS interactions, suggesting that the relationship between DHEAS levels and muscle parameters differs across the life span. In age-stratified models adjusted for confounders, serum DHEAS was an independent predictor of muscle strength (p <.02) and mass (p <.01), but only for men between 60 and 79 years of age. After adjusting these models for serum-free or bioavailable testosterone, results were unchanged. In men aged 60-79 years, circulating DHEAS is an independent correlate of muscle strength and calf muscle area. The possible causal role of declining DHEAS in age-related sarcopenia should be further explored in longitudinal studies.

DHEA supplementation to dexamethasone-treated rabbits alleviates oxidative stress in kidney-cortex and attenuates albuminuria.

PubMed

Kiersztan, Anna; Trojan, Nina; Tempes, Aleksandra; Nalepa, Paweł; Sitek, Joanna; Winiarska, Katarzyna; Usarek, Michał

2017-11-01

Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits. Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated. Administration of dexP resulted in accelerated generation of renal hydroxyl free radicals (HFR) and malondialdehyde (MDA), accompanied by diminished superoxide dismutase (SOD) and catalase activities and a dramatic rise in urinary albumin/creatinine ratio. Treatment with DHEA markedly reduced dexP-induced oxidative stress in kidney-cortex due to a decline in NADPH oxidase activity and enhancement of catalase activity. Moreover, DHEA effectively attenuated dexP-evoked albuminuria. Surprisingly, dexP-treated rabbits exhibited elevation of GSH/GSSG ratio, accompanied by a decrease in glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities as well as an increase in glucose-6-phosphate dehydrogenase (G6PDH) activity. Treatment with DHEA resulted in a decline in GSH/GSSG ratio and glutathione reductase (GR) activity, accompanied by an elevation of GPx activity. Interestingly, rabbits treated with both dexP and DHEA remained the control values of GSH/GSSG ratio. As the co-administration of DHEA with dexP resulted in (i) reduction of oxidative stress in kidney-cortex, (ii) attenuation of albuminuria and (iii) normalization of glutathione redox state, DHEA might limit several undesirable renal side effects during chronic GC treatment of patients suffering from allergies, asthma, rheumatoid arthritis and lupus. Moreover, its supplementation might be particularly beneficial for the therapy of patients with glucocorticoid-induced diabetes

Transport of the placental estriol precursor 16α-hydroxy-dehydroepiandrosterone sulfate (16α-OH-DHEAS) by stably transfected OAT4-, SOAT-, and NTCP-HEK293 cells.

PubMed

Schweigmann, H; Sánchez-Guijo, A; Ugele, B; Hartmann, K; Hartmann, M F; Bergmann, M; Pfarrer, C; Döring, B; Wudy, S A; Petzinger, E; Geyer, J; Grosser, G

2014-09-01

16α-Hydroxy-dehydroepiandrosterone sulfate (16α-OH-DHEAS) mainly originates from the fetus and serves as precursor for placental estriol biosynthesis. For conversion of 16α-OH-DHEAS to estriol several intracellular enzymes are required. However, prior to enzymatic conversion, 16α-OH-DHEAS must enter the cells by carrier mediated transport. To identify these carriers, uptake of 16α-OH-DHEAS by the candidate carriers organic anion transporter OAT4, sodium-dependent organic anion transporter SOAT, Na(+)-taurocholate cotransporting polypeptide NTCP, and organic anion transporting polypeptide OATP2B1 was measured in stably transfected HEK293 cells by LC-MS-MS. Furthermore, the study aimed to localize SOAT in the human placenta. Stably transfected OAT4-HEK293 cells revealed a partly sodium-dependent transport for 16α-OH-DHEAS with an apparent Km of 23.1 ± 5.1 μM and Vmax of 485.0 ± 39.1 pmol/mg protein/min, while stably transfected SOAT- and NTCP-HEK293 cells showed uptake only under sodium conditions with Km of 319.0 ± 59.5 μM and Vmax of 1465.8 ± 118.8 pmol/mg protein/min for SOAT and Km of 51.4 ± 9.9 μM and Vmax of 1423.3 ± 109.6 pmol/mg protein/min for NTCP. In contrast, stably transfected OATP2B1-HEK293 cells did not transport 16α-OH-DHEAS at all. Immunohistochemical studies and in situ hybridization of formalin fixed and paraffin embedded sections of human late term placenta showed expression of SOAT in syncytiotrophoblasts, predominantly at the apical membrane as well as in the vessel endothelium. In conclusion, OAT4, SOAT, and NTCP were identified as carriers for the estriol precursor 16α-OH-DHEAS. At least SOAT and OAT4 seem to play a functional role for the placental estriol synthesis as both are expressed in the syncytiotrophoblast of human placenta. Copyright © 2014 Elsevier Ltd. All rights reserved.

Serum DHEA and Its Sulfate Are Associated With Incident Fall Risk in Older Men: The MrOS Sweden Study.

PubMed

Ohlsson, Claes; Nethander, Maria; Karlsson, Magnus K; Rosengren, Björn E; Ribom, Eva; Mellström, Dan; Vandenput, Liesbeth

2018-03-12

The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. Many of the actions of DHEAS are considered to be mediated through metabolism into androgens and estrogens in peripheral target tissues. The predictive value of serum DHEA and DHEAS for the likelihood of falling is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEA and DHEAS levels and incident fall risk in a large cohort of older men. Serum DHEA and DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2516, age 69 to 81 years). Falls were ascertained every 4 months by mailed questionnaires. Associations between steroid hormones and falls were estimated by generalized estimating equations. During a mean follow-up of 2.7 years, 968 (38.5%) participants experienced a fall. High serum levels of both DHEA (odds ratio [OR] per SD increase 0.85; 95% CI, 0.78 to 0.92) and DHEAS (OR 0.88, 95% CI, 0.81 to 0.95) were associated with a lower incident fall risk in models adjusted for age, BMI, and prevalent falls. Further adjustment for serum sex steroids or age-related comorbidities only marginally attenuated the associations between DHEA or DHEAS and the likelihood of falling. Moreover, the point estimates for DHEA and DHEAS were only slightly reduced after adjustment for lean mass and/or grip strength. Also, the addition of the narrow walk test did not substantially alter the associations between serum DHEA or DHEAS and fall risk. Finally, the association with incident fall risk remained significant for DHEA but not for DHEAS after simultaneous adjustment for lean mass, grip strength, and the narrow walk test. This suggests that the associations between DHEA and DHEAS and falls are only partially mediated via muscle mass, muscle strength, and/or balance. In conclusion, older men with

Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats.

PubMed

Hulin, Mary W; Lawrence, Michelle N; Amato, Russell J; Weed, Peter F; Winsauer, Peter J

2015-03-01

The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and Drug Administration (FDA)-approved pharmacotherapies, naltrexone and acamprosate. Experiment 1 assessed the effects of different doses of DHEA, pregnanolone, naltrexone, and acamprosate on both ethanol- and food-maintained responding under a multiple fixed-ratio (FR)-10 FR-20 schedule, respectively. Experiment 2 assessed the effects of different mean intervals of food presentation on responding for ethanol under a FR-10 variable-interval (VI) schedule, whereas Experiment 3 assessed the effects of a single dose of each drug under a FR-10 VI-80 schedule. In Experiment 1, all four drugs dose-dependently decreased response rate for both food and ethanol, although differences in the rate-decreasing effects were apparent among the drugs. DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding, whereas the reverse was true for naltrexone. Acamprosate decreased responding for both reinforcers with equal potency. In Experiment 2, different mean intervals of food presentation significantly affected the number of food reinforcers obtained per session; however, changes in the number of food reinforcements did not significantly affect responding for ethanol. Under the FR-10 VI-80 schedule in Experiment 3, only naltrexone significantly decreased both the dose of alcohol presented and blood ethanol concentration (BEC). Acamprosate and pregnanolone had no significant effects on any of the dependent measures, whereas DHEA significantly decreased BEC, but did not significantly decrease response rate or the dose presented. In summary, DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding under a multiple FR-10 FR-20 schedule, and were more selective for decreasing ethanol self-administration than either naltrexone or

Hair Measurements of Cortisol, DHEA, and DHEA to Cortisol Ratio as Biomarkers of Chronic Stress among People Living with HIV in China: Known-Group Validation

PubMed Central

Li, Xiaoming; Zilioli, Samuele; Chen, Zheng; Deng, Huihua; Pan, Juxian

2017-01-01

Background Existing literature suggests that endocrine measures, including the steroid hormones of cortisol and Dehydroepiandrosterone (DHEA), as well as the DHEA to cortisol ratio in the human hair can be used as promising biomarkers of chronic stress among humans. However, data are limited regarding the validity of these measures as biomarkers of chronic stress among people living with HIV (PLWH), whose endocrine system or hypothalamic pituitary adrenal (HPA) axis may be affected by HIV infection and/or antiretroviral therapy (ART) medications. Method Using hair sample data and self-reported survey from 60 PLWH in China, we examined the validity of three endocrine measures among Chinese PLWH using a known-groups validation strategy. High-stress group (n = 30) and low-stress group (n = 30) of PLWH were recruited through individual assessment interviews by a local licensed psychologist. The endocrine measures in hair were extracted and assessed by LC-APCI-MS/MS method. Both bivariate and multivariate analyses were conducted to examine the associations between the endocrine measures and the stress level, and to investigate if the associations differ by ART status. Results The levels of endocrine measures among Chinese PLWH were consistent with existing studies among PLWH. Generally, this pilot study confirmed the association between endocrine measures and chronic stress. The high stress group showed higher level hair cortisol and lower DHEA to cortisol ratio. The higher stress group also reported higher scores of stressful life events, perceived stress, anxiety and depression. Hair cortisol level was positively related to anxiety; DHEA was negatively associated with stressful life events; and the DHEA to cortisol ratio was positively related to stressful life events and perceived stress. ART did not affect the associations between the endocrine measures and stress level. Conclusions Our findings suggest that hair cortisol and DHEA to cortisol ratio can be used as

Hormonal modulation of novelty processing in women: Enhanced under working memory load with high dehydroepiandrosterone-sulfate-to-dehydroepiandrosterone ratios.

PubMed

do Vale, Sónia; Selinger, Lenka; Martins, João Martin; Bicho, Manuel; do Carmo, Isabel; Escera, Carles

2016-11-10

Several studies have suggested that dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) may enhance working memory and attention, yet current evidence is still inconclusive. The balance between both forms of the hormone might be crucial regarding the effects that DHEA and DHEAS exert on the central nervous system. To test the hypothesis that higher DHEAS-to-DHEA ratios might enhance working memory and/or involuntary attention, we studied the DHEAS-to-DHEA ratio in relation to involuntary attention and working memory processing by recording the electroencephalogram of 22 young women while performing a working memory load task and a task without working memory load in an audio-visual oddball paradigm. DHEA and DHEAS were measured in saliva before each task. We found that a higher DHEAS-to-DHEA ratio was related to enhanced auditory novelty-P3 amplitudes during performance of the working memory task, indicating an increased processing of the distracter, while on the other hand there was no difference in the processing of the visual target. These results suggest that the balance between DHEAS and DHEA levels modulates involuntary attention during the performance of a task with cognitive load without interfering with the processing of the task-relevant visual stimulus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DHEA

MedlinePlus

... an immune condition characterized by dry mouth and dry eyes (Sjögren's syndrome), weak bones (osteoporosis), a form of muscular dystrophy called myotonic dystrophy, fibromyalgia, multiple sclerosis (MS), low levels of ... no DHEA at all, while others contained more than the labeled amount.

The effect of dehydroepiandrosterone (DHEA) supplementation on women with diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis.

PubMed

Qin, J C; Fan, L; Qin, A P

2017-01-01

To evaluate the effect of dehydroepiandrosterone (DHEA) therapy on the ovarian response and pregnancy outcome in patients with diminished ovarian reserve (DOR). Eligible studies, published before August 31, 2015, were identified from PubMed, EMBASE, the Cochrane library. Outcome measures were the number of retrieved oocytes, cancellation rate of IVF cycles, clinical pregnancy rate and miscarriage rate. We adopted Revman 5.0 software to pool the data from the eligible studies. A total of 9 studies, four were RCTs, four retrospective studies, one prospective studies, including 540 cases and 668 controls, were available for analysis. The pooled analysis showed that the clinical pregnancy rates were increased significantly in DOR patients who were pre-treated with DHEA (OR=1.47, 95% CI: 1.09-1.99), whereas no differences were found in the number of oocytes retrieved, the cancellation rate of IVF cycles and the miscarriage rate between the cases and controls (WMD= -0.69, 95% CI: -2.18-0.81; OR=0.74, 95% CI: 0.51-1.08; OR=0.34, 95% CI: 0.10-1.24). However, it is worth noting that when data were restricted to RCTs, there was a non-significant difference in the clinical pregnancy rate (OR=1.08, 95% CI: 0.67-1.73). We concluded that DHEA supplementation in DOR patients might improve the pregnancy outcomes. To further confirm this effect, more randomized controlled trials with large sample sizes are needed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

DHEA increases epithelial markers and decreases mesenchymal proteins in breast cancer cells and reduces xenograft growth.

PubMed

Colín-Val, Zaira; González-Puertos, Viridiana Yazmín; Mendoza-Milla, Criselda; Gómez, Erika Olivia; Huesca-Gómez, Claudia; López-Marure, Rebeca

2017-10-15

Breast cancer is one of the most common neoplasias and the leading cause of cancer death in women worldwide. Its high mortality rate is linked to a great metastatic capacity associated with the epithelial-mesenchymal transition (EMT). During this process, a decrease in epithelial proteins expression and an increase of mesenchymal proteins are observed. On the other hand, it has been shown that dehydroepiandrosterone (DHEA), the most abundant steroid in human plasma, inhibits migration of breast cancer cells; however, the underlying mechanisms have not been elucidated. In this study, the in vitro effect of DHEA on the expression pattern of some EMT-related proteins, such as E-cadherin (epithelial), N-cadherin, vimentin and Snail (mesenchymal) was measured by Western blot and immunofluorescence in MDA-MB-231 breast cancer cells with invasive, metastatic and mesenchymal phenotype. Also, the in vivo effect of DHEA on xenograft tumor growth in nude mice (nu - /nu - ) and on expression of the same epithelial and mesenchymal proteins in generated tumors was evaluated. We found that DHEA increased expression of E-cadherin and decreased N-cadherin, vimentin and Snail expression both in MD-MB-231 cells and in the formed tumors, possibly by DHEA-induced reversion of mesenchymal phenotype. These results were correlated with a tumor size reduction in mouse xenografts following DHEA administration either a week earlier or concurrent with breast cancer cells inoculation. In conclusion, DHEA could be useful in the treatment of breast cancer with mesenchymal phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

DHEA-induced ovarian hyperfibrosis is mediated by TGF-β signaling pathway.

PubMed

Wang, Daojuan; Wang, Wenqing; Liang, Qiao; He, Xuan; Xia, Yanjie; Shen, Shanmei; Wang, Hongwei; Gao, Qian; Wang, Yong

2018-01-10

The polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder with pathological mechanisms remain unclear. The following study investigates the ovarian hyperfibrosis forming via transforming growth factor-β (TGF-β) signaling pathway in Dehydroepiandrosterone (DHEA)- induced polycystic ovary syndrome (PCOS) rat model. We furthermore explored whether TGF-βRI inhibitor (SB431542) decreases ovarian fibrosis by counterbalancing the expression of fibrotic biomarkers. Thirty female Sprague-Dawley rats were randomly divided into Blank group (n = 6), Oil group (n = 6), and Oil + DHEA-induced model group (n = 6 + 12). The model groups were established by subcutaneous injection of DHEA for 35 consecutive days. The 12 successful model rats were additionally divided in vehicle group (n = 6) and SB431542-treated group (n = 6). Vehicle group and SB431542-treated group, served as administration group and were intraperitoneally injected with DMSO and SB431542 for additional 14 consecutive days. Ovarian morphology, fibrin and collagen localization and expression in ovaries were detected using H&E staining, immunohistochemistry and Sirius red staining. The ovarian protein and RNA were examined using Western blot and RT-PCR. In DHEA-induced ovary in rat, fibrin and collagen had significantly higher levels, while the main fibrosis markers (TGF-β, CTGF, fibronectin, a-SMA) were obviously upregulated. SB431542 significantly reduced the expression of pro-fibrotic molecules (TGF-β, Smad3, Smad2, a-SMA) and increased anti-fibrotic factor MMP2. TGF-βRI inhibitor (SB431542) inhibits the downstream signaling molecules of TGF-β and upregulates MMP2, which in turn prevent collagen deposition. Moreover, ovarian hyperfibrosis in DHEA-induced PCOS rat model could be improved by TGF-βRI inhibitor (SB431542) restraining the transcription of accelerating fibrosis genes and modulating EMT mediator.

Exposure to acute stress enhances decision-making competence: Evidence for the role of DHEA.

PubMed

Shields, Grant S; Lam, Jovian C W; Trainor, Brian C; Yonelinas, Andrew P

2016-05-01

Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations between decision-making competence and adrenal hormones. Participants in the stress induction group showed enhanced decision-making competence, relative to controls. Further, although both cortisol and dehydroepiandrosterone (DHEA) reactivity predicted decision-making competence when considered in isolation, DHEA was a significantly better predictor than cortisol when both hormones were considered simultaneously. Thus, our results show that exposure to acute stress can have beneficial effects on the cognitive ability underpinning real-world decision-making and that this effect relates to DHEA reactivity more than cortisol. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exposure to Acute Stress Enhances Decision-Making Competence: Evidence for the Role of DHEA

PubMed Central

Shields, Grant S.; Lam, Jovian C. W.; Trainor, Brian C.; Yonelinas, Andrew P.

2016-01-01

Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations between decision-making competence and adrenal hormones. Participants in the stress induction group showed enhanced decision-making competence, relative to controls. Further, although both cortisol and dehydroepiandrosterone (DHEA) reactivity predicted decision-making competence when considered in isolation, DHEA was a significantly better predictor than cortisol when both hormones were considered simultaneously. Thus, our results show that exposure to acute stress can have beneficial effects on the cognitive ability underpinning real-world decision-making and that this effect relates to DHEA reactivity more than cortisol. PMID:26874561

Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels in combat veterans with or without a history of suicide attempt.

PubMed

Sher, L; Flory, J; Bierer, L; Makotkine, I; Yehuda, R

2018-05-22

The goal of this study was to determine whether combat veterans who have made a suicide attempt postdeployment can be distinguished from combat veterans who have never made a suicide attempt based on differences in psychological and biological variables. Demographic and clinical parameters of suicide attempters and non-attempters were assessed. Blood samples were assayed for dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS). Suicide attempters had higher Scale for Suicidal Ideation and Montgomery-Åsberg Depression Rating Scale (MADRS)-suicidal thoughts item scores in comparison with non-attempters. There was a trend toward higher MADRS scores in the suicide attempter group compared with non-attempters. Suicide attempters had significantly lower levels of DHEA and DHEAS compared with non-attempters. Scale for Suicidal Ideation scores in all study participants combined negatively correlate with DHEA and DHEAS levels. DHEAS levels negatively correlate with Scale for Suicidal Ideation scores in suicide non-attempters but not in suicide attempters. DHEA/DHEAS ratios positively correlate with total adolescence aggression scores, total adulthood aggression scores, and total aggression scale scores in suicide attempters but not in suicide non-attempters. There are psychobiological differences between combat veterans with or without a history of suicidal behaviour. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Saliva DHEAS Changes in Patients Suffering from Psychopathological Disorders Arising from Bullying at Work

ERIC Educational Resources Information Center

Lac, Gerard; Dutheil, Frederic; Brousse, Georges; Triboulet-Kelly, Celine; Chamoux, Alain

2012-01-01

Background: Psychological disorders arising from bullying at work (BW) are common. The relationship between these disorders and putative markers is not well established. Aims: To measure saliva dehydroepiandrosterone sulphate (DHEAS) and saliva cortisol as putative markers in individuals suffering from BW. Methods: Forty one subjects suffering…

Protection against Acute Lethal Viral Infections with the Native Steroid Dehydroepiandrosterone (DHEA)

DTIC Science & Technology

1988-01-01

of gout , hyperlipemia, and in post-coronary patients Protection Against Viral Inftiom With DHEA 311 [Regelson, 19881. In animal models [Yen, 19771 and...3333. Johnson DA, Schultz LD, Bedigian HG (1982): Immunodeficiency and reticulum cell sarcoma in mice segregating for HRS/J and SJL/J genes . Leukemia

Investigating relations among stress, sleep and nail cortisol and DHEA.

PubMed

Doan, Stacey N; DeYoung, Gerrit; Fuller-Rowell, Thomas E; Liu, Cindy; Meyer, Jerrold

2018-03-01

In the current study, we present data investigating the relationships among stress, sleep disturbance, self-control, and levels of cortisol (CORT) and dehydroepiandrosterone (DHEA) in fingernail clippings. Currently, hair CORT is the only routinely used noninvasive, validated, biomarker of chronic exposure to stress-related hormones. Nail clippings represent an important potential alternative sample matrix for assessing chronic hormone exposure, as it offers a different timeline of hormone incorporation than scalp hair, and may be obtainable from populations in which hair either is lacking or is unavailable for cultural reasons. Moreover, there is established precedent for using fingernail clippings to attain biomarker data. However, the value of nail hormone assessment for psychological research is currently unknown due to a paucity of information on the relations between nail hormone concentrations and environmental or psychological variables. In the present study, we collected data from a low income, minority population (N = 47; 97% African American) to demonstrate feasibility and acceptability of nail collection and analysis of the adrenal steroids CORT and DHEA. Participants reported on perceived stress, sleep and self-control abilities. Correlational analyses suggest that exposure to stressful events, disturbances in sleep and waking were associated with higher levels of nail DHEA, while self-control was associated with higher levels of nail CORT. We discuss the potential importance of this methodology for investigating biological, behavioral, and subjective indices of stress and well-being.

Diurnal patterns and associations among salivary cortisol, DHEA and alpha-amylase in older adults.

PubMed

Wilcox, Rand R; Granger, Douglas A; Szanton, Sarah; Clark, Florence

2014-04-22

Cortisol and dehydroepiandrosterone (DHEA) are considered to be valuable markers of the hypothalamus-pituitary-adrenal (HPA) axis, while salivary alpha-amylase (sAA) reflects the autonomic nervous system. Past studies have found certain diurnal patterns among these biomarkers, with some studies reporting results that differ from others. Also, some past studies have found an association among these three biomarkers while other studies have not. This study investigates these patterns and associations in older adults by taking advantage of modern statistical methods for dealing with non-normality, outliers and curvature. Basic characteristics of the data are reported as well, which are relevant to understanding the nature of any patterns and associations. Boxplots were used to check on the skewness and presence of outliers, including the impact of using simple transformations for dealing with non-normality. Diurnal patterns were investigated using recent advances aimed at comparing medians. When studying associations, the initial step was to check for curvature using a non-parametric regression estimator. Based on the resulting fit, a robust regression estimator was used that is designed to deal with skewed distributions and outliers. Boxplots indicated highly skewed distributions with outliers. Simple transformations (such as taking logs) did not deal with this issue in an effective manner. Consequently, diurnal patterns were investigated using medians and found to be consistent with some previous studies but not others. A positive association between awakening cortisol levels and DHEA was found when DHEA is relatively low; otherwise no association was found. The nature of the association between cortisol and DHEA was found to change during the course of the day. Upon awakening, cortisol was found to have no association with sAA when DHEA levels are relatively low, but otherwise there is a negative association. DHEA was found to have a positive association with s

Steroid conversion with CYP106A2 - production of pharmaceutically interesting DHEA metabolites.

PubMed

Schmitz, Daniela; Zapp, Josef; Bernhardt, Rita

2014-06-05

Steroids are lipophilic compounds with a gonane skeleton and play an important role in higher organisms. Due to different functionalizations - mainly hydroxylations - at the steroid molecule, they vary highly in their mode of action. The pharmaceutical industry is, therefore, interested in hydroxysteroids as therapeutic agents. The insertion of hydroxyl groups into a steroid core, however, is hardly accomplishable by classical chemical means; that is because microbial steroid hydroxylations are investigated and applied since decades. CYP106A2 is a cytochrome P450 monooxygenase from Bacillus megaterium ATCC 13368, which was first described in the late 1970s and which is capable to hydroxylate a variety of 3-oxo-delta4 steroids at position 15beta. CYP106A2 is a soluble protein, easy to express and to purify in high amounts, which makes this enzyme an interesting target for biotechnological purposes. In this work a focused steroid library was screened in vitro for new CYP106A2 substrates using a reconstituted enzyme assay. Five new substrates were identified, including dehydroepiandrosterone and pregnenolone. NMR-spectroscopy revealed that both steroids are mainly hydroxylated at position 7beta. In order to establish a biotechnological system for the preparative scale production of 7beta-hydroxylated dehydroepiandrosterone, whole-cell conversions with growing and resting cells of B. megaterium ATCC1336 the native host of CYP1062 and also with resting cells of a recombinant B. megaterium MS941 strain overexpressing CYP106A2 have been conducted and conversion rates of 400 muM/h (115 mg/l/h) were obtained. Using the B. megaterium MS941 overexpression strain, the selectivity of the reaction was improved from 0.7 to 0.9 for 7beta-OH-DHEA. In this work we describe CYP106A2 for the first time as a regio-selective hydroxylase for 3-hydroxy-delta5 steroids. DHEA was shown to be converted to 7beta-OH-DHEA which is a highly interesting human metabolite, supposed to act as

Dehydroepiandrosterone and multiple measures of functional immunity in young adults.

PubMed

Prall, Sean P; Muehlenbein, Michael P

2015-01-01

Human immune function is strongly influenced by variation in hormone concentrations. The adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) are thought to be beneficial to immune function and disease resistance, but physiologically interact with testosterone and cortisol. We predict that DHEA and DHEA-S will interact with these other hormones in determining immunological outcomes. Understanding the interactive effects of these hormones will aid in understanding variability in immunocompetence and clarify discrepancies in human studies of androgen-immune interactions. Thirty-eight participants collected morning saliva over three days, from which concentrations of DHEA, DHEA-S, testosterone, and cortisol were measured, as well as salivary bacteria killing ability to measure innate immune function. From blood collection, serum was collected to measure innate immune function via a hemolytic complement assay, and whole blood collected and processed to measure proliferative responses of lymphocytes in the presence of mitogens. DHEA was negatively correlated with T cell proliferation, and positively correlated with salivary bacteria killing in male participants. Additionally, using regression models, DHEA-S was negatively associated with hemolytic complement activity, but interaction variables did not yield statistically significant relationships for any other outcome measure. While interactions with other hormones did not significantly relate with immune function measures in this sample, DHEA and DHEA-S did differentially impact multiple branches of the immune system. Generally characterized as immunosupportive in action, DHEA is shown to inhibit certain facets of innate and cell-mediated immunity, suggesting a more complex role in regulating immunocompetence. © 2015 Wiley Periodicals, Inc.

Effects of Methylphenidate and Bupropion on DHEA-S and Cortisol Plasma Levels in Attention-Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Lee, Moon-Soo; Yang, Jae-Won; Ko, Young-Hoon; Han, Changsu; Kim, Seung-Hyun; Lee, Min-Soo; Joe, Sook-Haeng; Jung, In-Kwa

2008-01-01

We evaluated plasma levels of DHEA-S and cortisol before and after treating ADHD patients with one of two medications: methylphenidate (n = 12) or bupropion (n = 10). Boys with ADHD (combined type) were evaluated with the Korean ADHD rating scale (K-ARS) and the computerized ADHD diagnostic system (ADS). All assessments were measured at baseline…

Steroid conversion with CYP106A2 – production of pharmaceutically interesting DHEA metabolites

PubMed Central

2014-01-01

Background Steroids are lipophilic compounds with a gonane skeleton and play an important role in higher organisms. Due to different functionalizations - mainly hydroxylations - at the steroid molecule, they vary highly in their mode of action. The pharmaceutical industry is, therefore, interested in hydroxysteroids as therapeutic agents. The insertion of hydroxyl groups into a steroid core, however, is hardly accomplishable by classical chemical means; that is because microbial steroid hydroxylations are investigated and applied since decades. CYP106A2 is a cytochrome P450 monooxygenase from Bacillus megaterium ATCC 13368, which was first described in the late 1970s and which is capable to hydroxylate a variety of 3-oxo-delta4 steroids at position 15beta. CYP106A2 is a soluble protein, easy to express and to purify in high amounts, which makes this enzyme an interesting target for biotechnological purposes. Results In this work a focused steroid library was screened in vitro for new CYP106A2 substrates using a reconstituted enzyme assay. Five new substrates were identified, including dehydroepiandrosterone and pregnenolone. NMR-spectroscopy revealed that both steroids are mainly hydroxylated at position 7beta. In order to establish a biotechnological system for the preparative scale production of 7beta-hydroxylated dehydroepiandrosterone, whole-cell conversions with growing and resting cells of B. megaterium ATCC1336 the native host of CYP1062 and also with resting cells of a recombinant B. megaterium MS941 strain overexpressing CYP106A2 have been conducted and conversion rates of 400 muM/h (115 mg/l/h) were obtained. Using the B. megaterium MS941 overexpression strain, the selectivity of the reaction was improved from 0.7 to 0.9 for 7beta-OH-DHEA. Conclusions In this work we describe CYP106A2 for the first time as a regio-selective hydroxylase for 3-hydroxy-delta5 steroids. DHEA was shown to be converted to 7beta-OH-DHEA which is a highly interesting human

Age-dependent and -independent associations between depression, anxiety, DHEAS, and cortisol: from the MIPH Industrial Cohort Studies (MICS).

PubMed

ó Hartaigh, Bríain; Loerbroks, Adrian; Thomas, G Neil; Engeland, Christopher G; Hollands, Mark A; Fischer, Joachim E; Bosch, Jos A

2012-07-01

There is a well-established link between dysphoric mood and endocrine dysregulation, but the strength of this association may vary with age. In order to investigate this possibility we assessed anxiety and depression with overnight urinary cortisol and plasma dehydroepiandrosterone-sulphate (DHEAS) in 608 factory employees ranging between 21 and 62 years. As expected, DHEAS declined with age (r=-0.54, P<0.001) while there was a modest age-related increase in nocturnal cortisol (r=0.17, P<0.001). Depressive symptoms were associated with higher nocturnal cortisol (β=0.19, P<0.001), independent of age. While the association between anxiety and cortisol (age by anxiety interaction: β=0.11, P<0.05) became stronger with age, there was a similar decline in the DHEAS/cortisol ratio in high-anxious middle-aged adults (β=-0.10, P=0.018). The current findings suggest that dysphoric mood, and in particular anxiety, may exacerbate the effects of aging on cortisol release. Prospective studies are needed to determine the causal relations between dysphoric mood, cortisol and DHEAS across the lifespan. Copyright © 2011 Elsevier Ltd. All rights reserved.

PAPSS2 Deficiency Causes Androgen Excess via Impaired DHEA Sulfation—In Vitro and in Vivo Studies in a Family Harboring Two Novel PAPSS2 Mutations

PubMed Central

Oostdijk, Wilma; Idkowiak, Jan; Mueller, Jonathan W.; House, Philip J.; Taylor, Angela E.; O'Reilly, Michael W.; Hughes, Beverly A.; de Vries, Martine C.; Kant, Sarina G.; Santen, Gijs W. E.; Verkerk, Annemieke J. M. H.; Uitterlinden, André G.; Wit, Jan M.; Losekoot, Monique

2015-01-01

Context: PAPSS2 (PAPS synthase 2) provides the universal sulfate donor PAPS (3′-phospho-adenosine-5′-phosphosulfate) to all human sulfotransferases, including SULT2A1, responsible for sulfation of the crucial androgen precursor dehydroepiandrosterone (DHEA). Impaired DHEA sulfation is thought to increase the conversion of DHEA toward active androgens, a proposition supported by the previous report of a girl with inactivating PAPSS2 mutations who presented with low serum DHEA sulfate and androgen excess, clinically manifesting with premature pubarche and early-onset polycystic ovary syndrome. Patients and Methods: We investigated a family harboring two novel PAPSS2 mutations, including two compound heterozygous brothers presenting with disproportionate short stature, low serum DHEA sulfate, but normal serum androgens. Patients and parents underwent a DHEA challenge test comprising frequent blood sampling and urine collection before and after 100 mg DHEA orally, with subsequent analysis of DHEA sulfation and androgen metabolism by mass spectrometry. The functional impact of the mutations was investigated in silico and in vitro. Results: We identified a novel PAPSS2 frameshift mutation, c.1371del, p.W462Cfs*3, resulting in complete disruption, and a novel missense mutation, c.809G>A, p.G270D, causing partial disruption of DHEA sulfation. Both patients and their mother, who was heterozygous for p.W462Cfs*3, showed increased 5α-reductase activity at baseline and significantly increased production of active androgens after DHEA intake. The mother had a history of oligomenorrhea and chronic anovulation that required clomiphene for ovulation induction. Conclusions: We provide direct in vivo evidence for the significant functional impact of mutant PAPSS2 on DHEA sulfation and androgen activation. Heterozygosity for PAPSS2 mutations can be associated with a phenotype resembling polycystic ovary syndrome. PMID:25594860

DHEA-induced modulation of renal gluconeogenesis, insulin sensitivity and plasma lipid profile in the control- and dexamethasone-treated rabbits. Metabolic studies.

PubMed

Kiersztan, Anna; Nagalski, Andrzej; Nalepa, Paweł; Tempes, Aleksandra; Trojan, Nina; Usarek, Michał; Jagielski, Adam K

2016-02-01

In view of antidiabetic and antiglucocorticoid effects of dehydroepiandrosterone (DHEA) both in vitro and in vivo studies were undertaken: (i) to elucidate the mechanism of action of both dexamethasone phosphate (dexP) and DHEA on glucose synthesis in primary cultured rabbit kidney-cortex tubules and (ii) to investigate the influence of DHEA on glucose synthesis, insulin sensitivity and plasma lipid profile in the control- and dexP-treated rabbits. Data show, that in cultured kidney-cortex tubules dexP significantly stimulated gluconeogenesis by increasing flux through fructose-1,6-bisphosphatase (FBPase). DexP-induced effects were dependent only upon glucocorticoid receptor. DHEA decreased glucose synthesis via inhibition of glucose-6-phosphatase (G6Pase) and suppressed the dexP-induced stimulation of renal gluconeogenesis. Studies with the use of inhibitors of DHEA metabolism in cultured renal tubules showed for the first time that DHEA directly affects renal gluconeogenesis. However, in view of analysis of glucocorticoids and DHEA metabolites levels in urine, it seems likely, that testosterone may also contribute to DHEA-evoked effects. In dexP-treated rabbits, plasma glucose level was not altered despite increased renal and hepatic FBPase and G6Pase activities, while a significant elevation of both plasma insulin and HOMA-IR was accompanied by a decline of ISI index. It thus appears that increased insulin levels were required to maintain normoglycaemia and to compensate the insulin resistance. DHEA alone affected neither plasma glucose nor lipid levels, while it increased insulin sensitivity and diminished both renal and hepatic G6Pase activities. Surprisingly, DHEA co-administrated with dexP did not alter insulin sensitivity, while it partially suppressed the dexP-induced elevation of renal G6Pase activity and plasma cholesterol and triglyceride contents. As (i) gluconeogenic pathway in rabbit is similar to that in human, and (ii) DHEA counteracts several

Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause.

PubMed

Labrie, Fernand; Archer, David F; Koltun, William; Vachon, Andrée; Young, Douglas; Frenette, Louise; Portman, David; Montesino, Marlene; Côté, Isabelle; Parent, Julie; Lavoie, Lyne; Beauregard, Adam; Martel, Céline; Vaillancourt, Mario; Balser, John; Moyneur, Érick

2016-03-01

The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM). In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively. After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P < 0.0001), whereas the percentage of superficial cells increased by 8.44% over placebo (P < 0.0001), vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001), and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo (P = 0.0002). On the other hand, moderate to severe vaginal dryness present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared to baseline, or 0.27 unit over placebo (P = 0.004). At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect (P < 0.0001 for all comparisons with placebo). Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology. The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at

Dehydroepiandrosterone-sulfate is associated with cardiovascular reactivity to stress in women.

PubMed

Hirokawa, Kumi; Ohira, Tetsuya; Nagayoshi, Mako; Kajiura, Mitsugu; Imano, Hironori; Kitamura, Akihiko; Kiyama, Masahiko; Okada, Takeo; Iso, Hiroyasu

2016-07-01

Cardiovascular stress reactivity is a predictor of atherosclerosis and cardiac events. Dehydroepiandrosterone (DHEA) protects against cardiovascular diseases, but results among previous studies have been inconsistent. We investigated the association between dehydroepiandrosterone-sulfate (DHEA-s) and cardiovascular stress reactivity in Japanese women and men. Among 979 healthy Japanese subjects (641 women and 338 men), serum levels of DHEA-s, systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, heart rate variability, and peripheral blood flow were measured under rest and two types of task. Mean differences in measured variables during tasks and a post-task period were calculated as changes in stress reactivity. Variables of stress reactivity were adjusted for multiple potential confounding factors. In women, DHEA-s levels showed positive associations with changes in SBP and DBP (standardized beta=0.12, p=0.020; 0.17, 0.002, respectively). Stratification by menopausal status and other lifestyle factors (e.g., smoking status, alcohol consumption) were conducted. Significant positive associations remained in pre-menopausal (standardized beta=0.13, p=0.037; 0.18, 0.005), non-smoking (0.12, 0.010; 0.18, <0.001), and non-drinking women (0.14, 0.021; 0.21, 0.001), and women without a medical history (0.15, 0.020; 0.20, 0.001). In men, there was no significant association between DHEA-s levels and changes in stress reactivity. DHEA-s levels were positively associated with high blood-pressure reactivity to stress in women, and being menopausal, smoking, and alcohol consumption modified this association. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of dehydroepiandrosterone on functional innate immune responses to acute stress.

PubMed

Prall, Sean P; Larson, Emilee E; Muehlenbein, Michael P

2017-12-01

The androgen dehydroepiandrosterone (DHEA) responds to stress activation, exhibits anti-glucocorticoid properties, and modulates immunity in diverse ways, yet little is known of its role in acute stress responses. In this study, the effects of DHEA and its sulfate ester DHEA-S on human male immune function during exposure to an acute stressor is explored. Variation in DHEA, DHEA-S, testosterone, and cortisol, along with bacterial killing assays, was measured in response to a modified Trier Social Stress test in 27 young adult males. Cortisol was positively related to salivary innate immunity but only for participants who also exhibited high DHEA responses. Additionally, DHEA positively and DHEA-S negatively predicted salivary immunity, but the opposite was observed for serum-based innate immunity. The DHEA response to acute stress appears to be an important factor in stress-mediated immunological responses, with differential effects on immunity dependent upon the presence of other hormones, primarily cortisol and DHEA-S. These results suggest that DHEA plays an important role, alongside other hormones, in modulating immunological shifts during acute stress. Copyright © 2017 John Wiley & Sons, Ltd.

Physiological levels and action of dehydroepiandrosterone in Yucatan miniature swine.

PubMed

Tagliaferro, A R; Ronan, A M

2001-07-01

The biological role of dehydroepiandrosterone (DHEA) and its less active sulphated conjugate DHEAS was investigated in two experiments using Yucatan miniature swine. In experiment 1, plasma levels of both DHEA(S) among males were greater than female pigs that ranged in age from 0.3 to 84 mo old (P < 0.0001). In males, DHEA(S) were related inversely to serum triglycerides; DHEA was positively related to triglycerides in females (P < 0.01). In experiment 2, four 2-yr old male pigs, used as their own control, showed a 5% decrease in body weight, 11% increase in energy expenditure, 88% increase in lipid, and 100% decrease in glucose utilization (P < 0.0001) in response to DHEA vs. placebo treatments when adjusted for body weight. Plasma DHEA(S) were not different between treatment conditions. Glucose tolerance and plasma insulin levels were not different from controls. In vivo response to norepinephrine indicated beta-adrenergic sensitivity was altered by DHEA. Present findings suggest DHEA and/or its hormone products are important in modulating energy expenditure and lipid utilization for energy in male animals. The role of DHEA in energy metabolism and the difference between sexes warrant further investigation.

Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes

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

Yokokawa, Takumi; Sato, Koji; Iwanaka, Nobumasa

Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5′-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levelsmore » of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms. - Highlights: • We assessed whether dehydroepiandrosterone (DHEA) activates AMPK and PGC-1α. • DHEA exposure increased glucose uptake in C2C12 myotubes. • The phosphorylation levels of AMPK were elevated by DHEA exposure. • DHEA induced the expression of the genes PGC-1α and GLUT4. • AMPK might mediate the anti-obesity and health-promoting effects of DHEA.« less

Lower Serum DHEAS levels are associated with a higher degree of physical disability and depressive symptoms in middle-aged to older African American women

PubMed Central

Haren, Matthew T.; Malmstrom, Theodore K.; Banks, William A.; Patrick, Ping; Miller, Douglas K.; Morley, John E.

2007-01-01

Background Changes in androgen levels and associations with chronic disease, physical and neuropsychological function and disability in women over the middle to later years of life are not well understood and have not been extensively studied in African-American women. Aims The present cross-sectional analysis reports such levels and associations in community dwelling, African American women aged 49 – 65 years from St. Louis, Missouri. Methods A home-based physical examination and a health status questionnaire were administered to randomly sampled women. Body composition (DEXA), lower limb and hand-grip muscle strength, physical and neuropsychological function and disability levels were assessed. Blood was drawn and assayed for total testosterone (T), sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), oestradiol (E2), adiponectin, leptin, triglycerides, glucose, C-reactive protein (CRP) and cytokine receptors (sIL2r, sIL6r, sTNFr1 & sTNFr2). Multiple linear regression modelling was used to identify the best predictors of testosterone, DHEAS and Free Androgen Index (T/SHBG). Results Seventy-four percent of women were menopausal and a quarter of these were taking oestrogen therapy. DHEAS and E2 declined between the ages of 49 and 65 years, whereas total T, SHBG and FAI remained stable. Total T and DHEAS levels were strongly correlated. In this population sample there were no independent associations of either total T or FAI with indicators of functional limitations, disability or clinically relevant depressive symptoms. Unlike total T and FAI, lower DHEAS levels was independently associated with both higher IADL scores (indicating a higher degree of physical disability) and higher CESD scores (indicating a higher degree of clinically relevant depressive symptoms). Conclusion There is an age-related decline in serum DHEAS in African-American women. Lower DHEAS levels appear to be associated with a higher degree of physical disability and

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

PubMed

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

2017-01-01

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

Effects of ketamine-xylazine and isoflurane on insulin sensitivity in dehydroepiandrosterone sulfate-treated minipigs (Sus scrofa domestica).

PubMed

Heim, Kelly E; Morrell, Jesse S; Ronan, Anne M; Tagliaferro, Anthony R

2002-06-01

Isoflurane and ketamine-xylazine (KX) combinations are widely used veterinary anesthetics, KX being the particularly common agent for immobilizing swine. Results of previous studies indicate that KX and xylazine suppress insulin release. The steroid hormones, dehydroepiandrosterone (DHEA) and its sulfated form, dehydroepiandrosterone-sulfate (DHEAS), have variable effects on insulin sensitivity in animals. We evaluated the effect of DHEAS on plasma glucose and insulin concentrations in female Yucatan swine under KX and isoflurane anesthesia. A 2 x 2 factorial design was used. Twenty-four 17-week-old gilts were randomly assigned to receive vehicle (placebo) or DHEAS as part of an ongoing study. The KX was given intramuscularly to all animals prior to blood sample collection at weeks two and four. At week three, all animals received isoflurane by inhalation. During KX anesthesia, mean insulin concentration in DHEAS-treated and control groups approximated half the postisoflurane values (P < 0.001). While under isoflurane, the DHEAS group had significantly higher mean plasma insulin concentration and mean insulin-to-glucose ratio, compared with values for controls (P < 0.05). These findings are consistent with changes in insulin values following DHEAS treatment observed previously in nonanesthetized swine. The effect of DHEAS treatment was absent in animals under KX anesthesia. These results suggest that KX significantly decreases plasma insulin concentration and blunts DHEAS-associated insulin resistance in female minipigs.

The association of dehydroepiandrosterone and dehydroepiandrosterone sulfate with anxiety sensitivity and electronic diary negative affect among smokers with and without posttraumatic stress disorder.

PubMed

Van Voorhees, Elizabeth E; Dennis, Michelle F; McClernon, F Joseph; Calhoun, Patrick S; Buse, Natalie A; Beckham, Jean C

2013-08-01

Posttraumatic stress disorder (PTSD) is associated with increased smoking initiation, maintenance, and relapse. Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are neurosteroids that have been associated with mood measures as well as smoking status, and nicotine is associated with increased DHEA and DHEAS levels. Given the difficulties with mood experienced by smokers with PTSD, the purpose of the current study was to evaluate the association between negative affect and anxiety sensitivity with DHEA and DHEAS levels. Ninety-six smokers with and without PTSD provided blood samples for neurosteroid analyses and completed self-report measures of anxiety sensitivity and electronic diary ratings of negative affect. As expected, PTSD smokers reported higher levels of anxiety sensitivity (F(1,94) = 20.67, partial η2 = 0.18, P < 0.0001) and negative affect (F(1,91) = 7.98, partial η2 = 0.08, P = 0.006). After accounting for age and sex, DHEAS was significantly inversely associated with both anxiety sensitivity (F(3,92) = 6.97, partial η2 = 0.07, P = 0.01) and negative affect (F(3,87) = 10.52, partial η2 = 0.11, P = 0.002) across groups. Effect sizes indicated that these effects are moderate to high. No significant interactions of diagnosis and DHEA(S) levels with mood measures were detected. Given that nicotine is known to elevate DHEA(S) levels, these results suggest that DHEAS may serve as a biomarker of the association between mood and nicotine among smokers. Implications for the results include (1) the use of DHEAS measurement across time and across quit attempts and (2) the potential for careful use of DHEA supplementation to facilitate abstinence during smoking cessation.

Serum dehydroepiandrosterone sulphate, psychosocial factors and musculoskeletal pain in workers.

PubMed

Marinelli, A; Prodi, A; Pesel, G; Ronchese, F; Bovenzi, M; Negro, C; Larese Filon, F

2017-12-30

The serum level of dehydroepiandrosterone sulphate (DHEA-S) has been suggested as a biological marker of stress. To assess the association between serum DHEA-S, psychosocial factors and musculoskeletal (MS) pain in university workers. The study population included voluntary workers at the scientific departments of the University of Trieste (Italy) who underwent periodical health surveillance from January 2011 to June 2012. DHEA-S level was analysed in serum. The assessment tools included the General Health Questionnaire (GHQ) and a modified Nordic musculoskeletal symptoms questionnaire. The relation between DHEA-S, individual characteristics, pain perception and psychological factors was assessed by means of multivariable linear regression analysis. There were 189 study participants. The study population was characterized by high reward and low effort. Pain perception in the neck, shoulder, upper limbs, upper back and lower back was reported by 42, 32, 19, 29 and 43% of people, respectively. In multivariable regression analysis, gender, age and pain perception in the shoulder and upper limbs were significantly related to serum DHEA-S. Effort and overcommitment were related to shoulder and neck pain but not to DHEA-S. The GHQ score was associated with pain perception in different body sites and inversely to DHEA-S but significance was lost in multivariable regression analysis. DHEA-S was associated with age, gender and perception of MS pain, while effort-reward imbalance dimensions and GHQ score failed to reach the statistical significance in multivariable regression analysis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Effects of chromium(III) picolinate on cortisol and DHEAs secretion in H295R human adrenocortical cells.

PubMed

Kim, Beob G; Adams, Julye M; Jackson, Brian A; Lindemann, Merlin D

2010-02-01

Dietary chromium(III) picolinate (CrPic) effects on circulating steroid hormones have been reported in various experimental animals. However, direct effects of CrPic on adrenocortical steroidogenesis are uncertain. Therefore, the objective was to determine the effects of CrPic on cortisol and dehydroepiandrosterone sulfate (DHEAs) secretion from H295R cells. In experiment 1, a 24-h exposure to CrPic (0 to 200 microM) had both linear (p < 0.001) and quadratic (p < 0.001) effects on cortisol secretion from forskolin-stimulated cells with the highest cortisol secretion at 0.1 microM of CrPic and the lowest at 200 microM of CrPic. In experiment 2, a 48-h exposure to CrPic (200 microM) decreased cortisol (p < 0.07) release from forskolin-stimulated cells during a 24-h collection period. In experiment 3, a 48-h exposure to CrPic (100 microM) decreased cortisol (p < 0.05) and DHEAs (p < 0.01) from forskolin-stimulated cells during a 24-h sampling period. In experiment 4, a 24-h exposure to forskolin followed by a 24-h exposure to both forskolin and CrPic (100 and 200 microM) decreased both cortisol and DHEAs secretion (p < 0.01). This study suggests that at high concentrations, CrPic inhibits aspects of steroidogenesis in agonist-stimulated adrenocortical cells.

Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage.

PubMed

Naylor, Jennifer C; Hulette, Christine M; Steffens, David C; Shampine, Lawrence J; Ervin, John F; Payne, Victoria M; Massing, Mark W; Kilts, Jason D; Strauss, Jennifer L; Calhoun, Patrick S; Calnaido, Rohana P; Blazer, Daniel G; Lieberman, Jeffrey A; Madison, Roger D; Marx, Christine E

2008-08-01

It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer's disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer's Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.

Dehydroepiandrosterone Sulfate Level Varies Nonlinearly with Symptom Severity in Major Depressive Disorder

PubMed Central

Uh, Dasom; Jeong, Hyun-Ghang; Choi, Kwang-Yeon; Oh, So-Young; Lee, Suji; Kim, Seung-Hyun; Joe, Sook-Haeng

2017-01-01

Objective The pathophysiology of major depressive disorder (MDD) is still not well understood. Conflicting results for surrogate biomarkers in MDD have been reported, which might be a consequence of the heterogeneity of MDD patients. Therefore, we aim to investigate how the severity of depression and various symptom domains are related to the levels of dehydroepiandrosterone sulfate (DHEA-s) in MDD patients. Methods We recruited 117 subjects from a general practice. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Depressive symptoms were divided into three subdomains according to BDI items; somatic symptoms, guilt and failure, and mood and inhibition. Results In subjects with very-mild-to-moderate depression, the DHEA-s level increased as BDI score did. However, the DHEA-s levels in the subjects with severe depression were significantly lower than in subjects with moderate depression (p=0.003). DHEA-s level was correlated with the BDI subscore for guilt and failure in very-mild-to-moderate depression (r=0.365, p=0.006). Conclusion The DHEA-s level appears to be indicative of MDD severity with respect to depressive symptoms, especially regarding guilt and failure. Our findings suggest that the upregulation of DHEA-s may be a part of a compensatory process in very-mild-to-moderate depression, and the failure of this compensation mechanism may underlie the development of severe depression. PMID:28449564

Effects of dehydroepiandrosterone supplementation during stressful military training: a randomized, controlled, double-blind field study.

PubMed

Taylor, Marcus K; Padilla, Genieleah A; Stanfill, Katherine E; Markham, Amanda E; Khosravi, Jasmine Y; Ward, Michael D Dial; Koehler, Matthew M

2012-01-01

Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are anabolic prehormones involved in the synthesis of testosterone. Both have been shown to exert neuroprotective effects during stress. In this randomized, controlled, double-blind field study, we examined the effects of a 12-day DHEA regimen on stress indices in military men undergoing survival training. Forty-eight men were randomized to either a DHEA treatment group or placebo control group. The treatment group received 50 mg of oral DHEA supplementation daily for 5 days during classroom training followed by 7 days of 75 mg during stressful field operations. Control subjects received identical placebo pills. Salivary assays (DHEA[S], testosterone, and cortisol) were conducted at four time points: distal pre-stress (T1), proximal pre-stress (T2), mock-captivity stress (T3), and 24 h recovery (T4). Subjective distress was also assessed at T1, T3, and T4. As expected, DHEA treatment resulted in higher salivary concentrations of DHEA and DHEAS during daily living, mock-captivity stress, and recovery. Similar patterns were observed for salivary markers of anabolic balance: DHEA/cortisol, DHEAS/cortisol, and testosterone/cortisol concentration ratios. Despite notable time effects, no group differences emerged for subjective distress. A brief, low dose DHEA regimen yielded large increases in salivary DHEA(S) concentrations and enhanced anabolic balance throughout sustained military stress. These physiological changes did not extrapolate to subjective distress.

Dehydroepiandrosterone Attenuates Cocaine-Seeking Behaviour Independently of Corticosterone Fluctuations.

PubMed

Maayan, R; Hirsh, L; Yadid, G; Weizman, A

2015-11-01

The neurosteroid dehydroepiandrosterone (DHEA) is involved in the pathophysiology of several psychiatric disorders, including cocaine addiction. We have previously shown that DHEA attenuates cocaine-seeking behaviour, and also that DHEA decreases corticosterone (CORT) levels in plasma and the prefrontal cortex. Previous studies have found that rats demonstrate cocaine-seeking behaviour only when the level of CORT reaches a minimum threshold. In the present study, we investigated whether the attenuating effect of DHEA on cocaine seeking is a result of it reducing CORT levels rather than a result of any unique neurosteroid properties. Rats received either daily DHEA injections (2 mg/kg, i.p.) alone, daily DHEA (2 mg/kg, i.p.) with CORT infusion (to maintain stable basal levels of CORT; 15 mg/kg, s.c.) or vehicle (i.p.) as control, throughout self-administration training and extinction sessions. We found that both DHEA-treated and DHEA + CORT-treated groups showed a significantly lower number of active lever presses compared to controls throughout training and extinction sessions, as well as at cocaine-primed reinstatement. DHEA-treated rats showed lower CORT levels throughout the experimental phases compared to DHEA + CORT-treated and control rats. Additionally, we show that DHEA administered to cocaine-trained rats throughout extinction sessions, or immediately before reinstatement, attenuated cocaine seeking. These findings indicate that DHEA attenuates cocaine-seeking behaviour independently of fluctuations in CORT levels. © 2015 British Society for Neuroendocrinology.

Biocompatibility of poly(etherurethane urea) containing dehydroepiandrosterone.

PubMed

Collier, T; Tan, J; Shive, M; Hasan, S; Hiltner, A; Anderson, J

1998-08-01

Poly(etherurethane urea) (PEUU) elastomers, with their broad range of mechanical properties and high biocompatibility, are used clinically for medical applications. However, the possibility exists for the ether soft segment of PEUU to degrade in long-term uses. To retard degradation, antioxidants that scavenge reactive oxygen intermediates are added. In this study, we incorporated dehydroepiandrosterone (DHEA), which functions by the alternate mechanism of modulating or down-regulating adherent macrophage activity, to retard the biodegradation of PEUUs. Biocompatibility of PEUU samples containing 1% DHEA, 5% DHEA, and 5% vitamin E (alpha-tocopherol) by weight were studied in vivo and in vitro. The biocompatibility was initially evaluated by examination of the inflammatory cellular exudate. Compared to PEUU without additives and PEUU with 5% vitamin E, the addition of 5% DHEA to PEUU caused a decrease in the total leukocyte exudate concentration at 4 days. The addition of 5% DHEA also caused lower macrophage adhesion and FBGC formation compared to the other materials at 7 days. Despite these short-term effects, the biocompatibility at later time points (14, 21, and 70 days) was similar for all materials. Transmission infrared analysis of the materials revealed that more than 70% of the DHEA had leached out of the samples by 3 days implantation. Furthermore, through attenuated total reflectance Fourier transform analysis and scanning electron microscopy, it was determined that unlike vitamin E, DHEA did not enhance long-term PEUU biostability. The effect of DHEA on inflammatory cell activity appeared to be dose dependent, with improved biocompatibility in vivo for higher loading levels of DHEA, but the overall effect was limited owing to the rapid diffusion of the water-soluble DHEA from the PEUU.

Diurnal and stress-reactive dehydroepiandrosterone levels and telomere length in youth

PubMed Central

Dismukes, Andrew R; Meyer, Vanessa J; Shirtcliff, Elizabeth A; Theall, Katherine P; Esteves, Kyle C

2016-01-01

The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA) and telomere length (TL) in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C). TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05), while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging. PMID:27221260

Diurnal and stress-reactive dehydroepiandrosterone levels and telomere length in youth.

PubMed

Dismukes, Andrew R; Meyer, Vanessa J; Shirtcliff, Elizabeth A; Theall, Katherine P; Esteves, Kyle C; Drury, Stacy S

2016-05-01

The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA) and telomere length (TL) in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C). TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05), while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging. © 2016 The authors.

HDL-associated dehydroepiandrosterone fatty acyl esters: enhancement of vasodilatory effect of HDL.

PubMed

Paatela, Hanna; Mervaala, Eero; Deb, Somdatta; Wähälä, Kristiina; Tikkanen, Matti J

2009-10-01

Dehydroepiandrosterone (DHEA) and high-density lipoprotein (HDL) are both vascular relaxants. In the circulation, HDL transports DHEA fatty acyl esters (DHEA-FAEs), which are naturally occurring lipophilic derivatives of DHEA. We studied in isolated rat mesenteric arteries whether HDL-associated DHEA-FAE improves the vasodilatory effect of HDL. To prepare DHEA-FAE-enriched HDL, we incubated DHEA with human plasma. After incubation, HDL was isolated, purified, and added in cumulative doses (0.1-125 microg/ml) to noradrenaline-precontracted rat arterial rings. DHEA-FAE-enriched HDL caused a dose-dependent relaxation (maximal 43+/-4%), which was significantly stronger than the effect of HDL from the control incubation without addition of DHEA (25+/-2%, p<0.001). When plasma incubation of DHEA was carried out in the presence of lecithin:cholesterol acyltransferase (LCAT) inhibitor, the relaxation response to HDL (25+/-3%) did not differ from the control HDL (p=0.98). Pretreatment of the arterial rings with nitric oxide synthase (NOS) antagonist impaired the relaxation response to DHEA-FAE-enriched HDL (43+/-4% vs. 30+/-3%, p=0.008). Similar experiments were performed with 17beta-estradiol (E(2)). Compared to control HDL, E(2)-FAE-enriched HDL induced slightly but non-significantly stronger relaxation. DHEA-FAE-enriched HDL was a stronger vasodilator than native HDL, and vascular relaxation was in part mediated by NOS, suggesting that DHEA-FAE may improve HDL's antiatherogenic function.

The pharmacokinetics and pharmacodynamics of dehydroepiandrosterone during use of an ethinylestradiol- and drospirenone-containing oral contraceptive.

PubMed

Zimmerman, Yvette; Coelingh Bennink, Herjan J T; Wouters, Wout; Ebes, Frieda; Fauser, Bart C J M

2013-12-01

Combined oral contraceptives (COCs) reduce the levels of ovarian and adrenal androgens. Co-administration of dehydroepiandrosterone (DHEA) may normalise androgen levels during COC use. To investigate the effect of the addition of DHEA to a COC on the pharmacokinetics (PK) and pharmacodynamics (PD) of DHEA and its sulphate (DHEA-S), and on levels of total and free testosterone (T). In a prospective, randomised, double-blind, placebo-controlled, cross-over study involving 21 female volunteers, the PK and PD of DHEA and DHEA-S were investigated during the use of one cycle of a COC containing 30 μg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) with and without daily co-administration of 50 mg DHEA. Treatment during one cycle with a COC containing EE and DRSP reduces the exposure to DHEA and DHEA-S by at least 20%. This loss of adrenal androgens can be fully compensated by daily oral co-administration of 50 mg DHEA. With DHEA co-administration total T levels rise significantly (1.44 nmol/L with DHEA vs. 0.82 nmol/L with placebo; p < 0.001). Free T levels decrease significantly with both DHEA and placebo treatment, but significantly less during co-administration of DHEA (6.34 pmol/L with DHEA vs. 3.96 pmol/L with placebo; p < 0.001). By adding DHEA to a COC the loss of adrenal and ovarian androgens can be restored.

Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte proliferation, differentiation, and glucose uptake

PubMed Central

McNelis, Joanne C.; Manolopoulos, Konstantinos N.; Gathercole, Laura L.; Bujalska, Iwona J.; Stewart, Paul M.; Tomlinson, Jeremy W.

2013-01-01

Glucocorticoids increase adipocyte proliferation and differentiation, a process underpinned by the local reactivation of inactive cortisone to active cortisol within adipocytes catalyzed by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The adrenal sex steroid precursor dehydroepiandrosterone (DHEA) has been shown to inhibit 11β-HSD1 in murine adipocytes; however, rodent adrenals do not produce DHEA physiologically. Here, we aimed to determine the effects and underlying mechanisms of the potential antiglucocorticoid action of DHEA and its sulfate ester DHEAS in human preadipocytes. Utilizing a human subcutaneous preadipocyte cell line, Chub-S7, we examined the metabolism and effects of DHEA in human adipocytes, including adipocyte proliferation, differentiation, 11β-HSD1 expression, and activity and glucose uptake. DHEA, but not DHEAS, significantly inhibited preadipocyte proliferation via cell cycle arrest in the G1 phase independent of sex steroid and glucocorticoid receptor activation. 11β-HSD1 oxoreductase activity in differentiated adipocytes was inhibited by DHEA. DHEA coincubated with cortisone significantly inhibited preadipocyte differentiation, which was assessed by the expression of markers of early (LPL) and terminal (G3PDH) adipocyte differentiation. Coincubation with cortisol, negating the requirement for 11β-HSD1 oxoreductase activity, diminished the inhibitory effect of DHEA. Further consistent with glucocorticoid-opposing effects of DHEA, insulin-independent glucose uptake was significantly enhanced by DHEA treatment. DHEA increases basal glucose uptake and inhibits human preadipocyte proliferation and differentiation, thereby exerting an antiglucocorticoid action. DHEA inhibition of the amplification of glucocorticoid action mediated by 11β-HSD1 contributes to the inhibitory effect of DHEA on human preadipocyte differentiation. PMID:24022868

Effects of short-term dehydroepiandrosterone supplementation on body composition in young athletes.

PubMed

Ostojic, Sergej M; Calleja, Julio; Jourkesh, Morteza

2010-02-28

Dehydroepiandrosterone (DHEA) is often promoted as a slimming and weight/fat loss agent and ingestion of DHEA may have hypolipidemic and anti-obesity properties. The main aim of this study was to examine the effects of acute DHEA intake on body composition and serum steroid hormones in young athletes. Twenty young (19 to 22 years) male soccer players were allocated into two randomly assigned trials in double-blind design by ingesting 100-mg daily oral DHEA or as placebo (PLA) for 28 days. Body mass was not affected by 4 weeks of DHEA supplementation (P > 0.05). No significant changes in body mass index (BMI), waist-to-hip ratio (WHR) and body fat or total muscle mass for the two groups were detected at the end of the trial (P > 0.05). There was no within- or between-group difference in arm fat index (AFI) and corrected mid-upper-arm muscle area (cAMA) (P > 0.05). Treatment with DHEA resulted in a significant increase of total testosterone, estradiol and DHEA-S levels in treated subjects versus the placebo group (P < 0.05). Results of this study suggest that DHEA supplementation has no beneficial effects on body composition in young competitive athletes.

High-fat diets exaggerate endocrine and metabolic phenotypes in a rat model of DHEA-induced PCOS.

PubMed

Zhang, Haolin; Yi, Ming; Zhang, Yan; Jin, Hongyan; Zhang, Wenxin; Yang, Jingjing; Yan, Liying; Li, Rong; Zhao, Yue; Qiao, Jie

2016-04-01

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder with unclear etiology and unsatisfactory management. Effects of diets on the phenotype of PCOS were not fully understood. In the present study, we applied 45 and 60% high-fat diets (HFDs) on a rat model of PCOS induced by postnatal DHEA injection. We found that both DHEA and DHEA+HFDs rats exhibited reproductive abnormalities, including hyperandrogenism, irregular cycles and polycystic ovaries. The addition of HFDs, especially 60% HFDs, exaggerated morphological changes of ovaries and a number of metabolic changes, including increased body weight and body fat content, impaired glucose tolerance and increased serum insulin levels. Results from qPCR showed that DHEA-induced increased expression of hypothalamic androgen receptor and LH receptor were reversed by the addition of 60% HFDs. In contrast, the ovarian expression of LH receptor and insulin receptor mRNA was upregulated only with the addition of 60% HFDs. These findings indicated that DHEA and DHEA+HFDs might influence PCOS phenotypes through distinct mechanisms: DHEA affects the normal function of hypothalamus-pituitary-ovarian axis through LH, whereas the addition of HFDs exaggerated endocrine and metabolic dysfunction through ovarian responses to insulin-related mechanisms. We concluded that the addition of HFDs yielded distinct phenotypes of DHEA-induced PCOS and could be used for studies on both reproductive and metabolic features of the syndrome. © 2016 Society for Reproduction and Fertility.

Serum dehydroepiandrosterone sulphate, total antioxidant capacity, and total oxidant status in central serous chorioretinopathy.

PubMed

Türkcü, Fatih Mehmet; Yüksel, Harun; Yüksel, Hatice; Sahin, Alparslan; Cinar, Yasin; Cingü, Abdullah Kürşat; Sahin, Muhammed; Caça, Ihsan

2014-01-01

The objective of this work is to evaluate plasma total antioxidant capacity (TAC), total oxidant status (TOS), and dehydroepiandrosterone sulphate (DHEA-S) levels in patients diagnosed with acute central serous chorioretinopathy (CSCR) and control samples. The TAC, TOS, and DHEA-S levels were assessed in the plasma of 46 CSCR patients and compared with 40 control samples. The TAC level was 1.16 ± 0.08 and 1.20 ± 0.09 mmol Trolox eq./l; TOS level was 28.77 ± 33.33 and 19.95 ± 10.42 μmol H202/l; DHEA-S level was 203.79 ± 84.75 μg/dl and 249.36 ± 122.93 μg/dl in the CSCR group and in the control group, respectively. The plasma TAC and DHEA-S values were significantly lower in the CSCR group than in the control group (p = 0.027 and p = 0.046, respectively). There was no significant difference between the CSCR and the control groups in terms of age, gender, and TOS levels (p > 0.05). We demonstrated that the levels of plasma DHEA-S and antioxidative parameters were reduced in CSCR. Our results suggest that the antioxidant defense system may be inadequate or corrupted in CSCR. Reduced DHEA-S level is one of the factors that trigger this insufficiency.

The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer.

PubMed

Tamae, Daniel; Mostaghel, Elahe; Montgomery, Bruce; Nelson, Peter S; Balk, Steven P; Kantoff, Philip W; Taplin, Mary-Ellen; Penning, Trevor M

2015-06-05

Prostate cancer is the second leading cause of cancer death in the United States. Treatment of localized high-risk disease and de novo metastatic disease frequently leads to relapse. These metastatic castration resistant prostate cancers (mCRPC) claim a high mortality rate, despite the extended survival afforded by the growing armamentarium of androgen deprivation, radiation and immunotherapies. Here, we review two studies of neoadjuvant treatment of high-risk localized prostate cancer prior to prostatectomy, the total androgen pathway suppression (TAPS) trial and the neoadjuvant abiraterone acetate (AA) trial. These two trials assessed the efficacy of the non-specific P450c17 inhibitor, ketoconazole and the specific P450c17 inhibitor, AA, to inhibit tissue and serum androgen levels. Furthermore, a novel and validated stable isotope dilution liquid chromatography electrospray ionization selected reaction monitoring mass spectrometry assay was used to accurately quantify adrenal and gonadal androgens in circulation during the course of these trials. The adrenal androgens, Δ(4)-androstene-3,17-dione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly reduced in the patients receiving ketoconazole or AA compared to those who did not. However, in both trials, a significant amount of DHEA-S (∼20 μg/dL) persists and thus may serve as a depot for intratumoral conversion to the potent androgen receptor ligands, testosterone (T) and 5α-dihydrotestosterone (DHT). The final step in conversion of Δ(4)-androstene-3,17-dione and 5α-androstanedione to T and DHT, respectively, is catalyzed by AKR1C3. We therefore present the case that in the context of the DHEA-S depot, P450c17 and AKR1C3 inhibition may be an effective combinatorial treatment strategy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Daily stressors and adult day service use by family caregivers: effects on depressive symptoms, positive mood, and dehydroepiandrosterone-sulfate.

PubMed

Zarit, Steven H; Whetzel, Courtney A; Kim, Kyungmin; Femia, Elia E; Almeida, David M; Rovine, Michael J; Klein, Laura Cousino

2014-12-01

This study examines effects of daily use of adult day service (ADS) programs by caregivers of individuals with dementia (IWD) on a salivary biomarker of stress reactivity, dehydroepiandrosterone-sulfate (DHEA-S), and whether these effects on DHEA-S are associated with daily variability in positive mood and depressive symptoms. We used a daily diary design of 8 consecutive days with alternation of intervention (ADS) and nonintervention days to evaluate within- and between-person effects of the intervention. Family caregivers (N = 151) of IWD who were using ADS were interviewed daily by telephone at home. Saliva samples were collected from caregivers five times a day for 8 consecutive days and were assayed for DHEA-S. Daily telephone interviews assessed daily stressors and mood. DHEA-S levels were significantly higher on days after ADS use. Daily DHEA-S levels covaried significantly with daily positive mood but not with depressive symptoms. These results demonstrate an association of ADS use by family caregivers and higher DHEA-S levels on the next day. Prior research has found that higher DHEA-S levels are protective against the physiologic damaging effects of stressor exposure and may reduce risks of illness. Regular use of ADS may help reduce depletion of DHEA-S and allow the body to mount a protective and restorative response to the physiologic demands of caregiving. To our knowledge, this is the first study to examine DHEA-S levels across the day in connection with an intervention that affected daily exposure to stressors. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Dehydroepiandrosterone protects male and female hippocampal neurons and neuroblastoma cells from glucose deprivation.

PubMed

Vieira-Marques, Claudia; Arbo, Bruno Dutra; Ruiz-Palmero, Isabel; Ortiz-Rodriguez, Ana; Ghorbanpoor, Samar; Kucharski, Luiz Carlos; Arevalo, Maria A; Garcia-Segura, Luis Miguel; Ribeiro, Maria Flávia M

2016-08-01

Dehydroepiandrosterone (DHEA) modulates neurogenesis, neuronal function, neuronal survival and metabolism, enhancing mitochondrial oxidative capacity. Glucose deprivation and hypometabolism have been implicated in the mechanisms that mediate neuronal damage in neurological disorders, and some studies have shown that these mechanisms are sexually dimorphic. It was also demonstrated that DHEA is able to attenuate the hypometabolism that is related to some neurodegenerative diseases, eliciting neuroprotective effects in different experimental models of neurodegeneration. The aim of this study was to evaluate the effect of DHEA on the viability of male and female hippocampal neurons and SH-SY5Y neuroblastoma cells exposed to glucose deprivation. It was observed that after 12h of pre-treatment, DHEA was able to protect SH-SY5Y cells from glucose deprivation for 6h (DHEA 10(-12), 10(-8) and 10(-6)M) and 8h (DHEA 10(-8)M). In contrast, DHEA was not neuroprotective against glucose deprivation for 12 or 24h. DHEA (10(-8)M) also protected SH-SY5Y cells when added together or even 1h after the beginning of glucose deprivation (6h). Furthermore, DHEA (10(-8)M) also protected primary neurons from both sexes against glucose deprivation. In summary, our findings indicate that DHEA is neuroprotective against glucose deprivation in human neuroblastoma cells and in male and female mouse hippocampal neurons. These results suggest that DHEA could be a promising candidate to be used in clinical studies aiming to reduce neuronal damage in people from both sexes. Copyright © 2016 Elsevier B.V. All rights reserved.

RHOG-DOCK1-RAC1 Signaling Axis Is Perturbed in DHEA-Induced Polycystic Ovary in Rat Model.

PubMed

Ubba, Vaibhave; Soni, Upendra Kumar; Chadchan, Sangappa; Maurya, Vineet Kumar; Kumar, Vijay; Maurya, Ruchika; Chaturvedi, Himanshu; Singh, Rajender; Dwivedi, Anila; Jha, Rajesh Kumar

2017-05-01

The function of RHOG, a RAC1 activator, was explored in the ovary during ovarian follicular development and pathological conditions. With the help of immunoblotting and immunolocalization, we determined the expression and localization of RHOG in normal (estrous cycle) and polycystic ovaries using Sprague Dawley (SD) rat model. Employing polymerase chain reaction and flow cytometry, we analyzed the transcript and expression levels of downstream molecules of RHOG, DOCK1, and RAC1 in the polycystic ovarian syndrome (PCOS) ovary along with normal antral follicular theca and granulosa cells after dehydroepiandrosterone (DHEA) supplementation. The effect of RHOG knockdown on DOCK1, VAV, and RAC1 expression was evaluated in the human ovarian cells (SKOV3), theca cells, and granulosa cells from SD rats with the help of flow cytometry. Oocyte at secondary follicles along with stromal cells showed optimal expression of RHOG. Immunoblotting of RHOG revealed its maximum expression at diestrus and proestrus, which was downregulated at estrus stage. Mild immunostaining of RHOG was also present in the theca and granulosa cells of the secondary and antral follicles. Polycystic ovary exhibited weak immunostaining for RHOG and that was corroborated by immunoblotting-based investigations. RHOG effectors DOCK1 and ELMO1 were found reduced in the ovary in PCOS condition/DHEA. RHOG silencing reduced the expression of DOCK1 and RAC1 in the theca and granulosa cells from SD rat antral follicles and that was mirrored in the human ovarian cells. Collectively, RHOG can mediate signaling through downstream effectors DOCK1 and RAC1 during ovarian follicular development (theca and granulosa cells and oocyte), but DHEA downregulated them in the PCOS ovary.

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

PubMed Central

Amato, Russell J.; Hulin, Mary W.; Winsauer, Peter J.

2012-01-01

Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxide, rauwolscine, and RO15-4513) were administered to male rats responding under a multiple schedule of food and ethanol presentation to determine their selectively for decreasing ethanol-maintained responding. DHEA and 7-keto DHEA significantly decreased both ethanol- and food-maintained responding, compared to control, while also decreasing blood ethanol concentration (BEC). Acute ethanol administration also decreased responding for both food and ethanol; however, ethanol-maintained responding was more potently decreased than food-maintained responding. BEC remained relatively stable after increasing ethanol doses. Among the other drugs tested, RO15-4513 was the most selective for decreasing ethanol-maintained responding compared to food-maintained responding, and it decreased BECs as ethanol-maintained responding decreased. The largest dose of rauwolscine significantly decreased responding for food, while not affecting ethanol-maintained responding compared to control. Low to intermediate doses of rauwolscine produced small, non-significant increases in ethanol-maintained responding and BECs. Chlordiazepoxide produced significant decreases in food-maintained responding and the dose of ethanol presented, but only at the highest dose tested. Although DHEA and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be valuable pharmacological tools in the development of new treatments for alcohol abuse and dependence. PMID:22473025

The bioequivalence of the contraceptive steroids ethinylestradiol and drospirenone is not affected by co-administration of dehydroepiandrosterone.

PubMed

Zimmerman, Yvette; Wouters, Wout; Coelingh Bennink, Herjan J T

2013-06-01

To study the effect of co-administration of 50 mg dehydroepiandrosterone (DHEA) on the bioequivalence of ethinylestradiol (EE) and drospirenone (DRSP) in women who were using a combined oral contraceptive (COC) containing 30 μg EE and 3 mg DRSP, and to estimate whether the addition of DHEA to this COC affects the serum levels and the bioequivalence of the synthetic contraceptive steroids. This was a randomised, double-blind, two-period crossover study. Participants received two EE/DRSP COC treatment cycles in random order, one with and one without daily 50 mg DHEA , separated by a 28-day wash-out cycle during which the subjects used an EE/levonorgestrel (LNG) COC without DHEA. Serum levels of EE and DRSP were measured according to a sampling scheme allowing pharmacokinetic evaluations. Addition of DHEA to an EE/DRSP COC had no effect on serum levels of EE and DRSP. The COC regimens with and without DHEA were bioequivalent. Oestradiol levels were equally suppressed during pill intake, whether with placebo or DHEA. Adding DHEA to a COC containing EE and DRSP does not affect the pharmacokinetic properties of EE and DRSP. Therefore, it will most likely not affect its contraceptive efficacy.

Decreased dehydroepiandrosterone sulphate levels in adolescents with post-traumatic stress disorder after single sexual trauma.

PubMed

Usta, Mirac Baris; Tuncel, Ozgur Korhan; Akbas, Seher; Aydin, Berna; Say, Gokce Nur

2016-01-01

Recent evidence shows that the hypothalamic-pituitary-adrenal (HPA) axis can be dysregulated in chronic sexual abuse victims with post-traumatic stress disorder (PTSD). We hypothesized that PTSD in adolescents exposed to a single sexual trauma may function as a chronic stressor leading to HPA-axis dysregulation. The objective of this study was to assess dehydroepiandrosterone sulphate (DHEA-S) and cortisol levels in female adolescents |with single sexual trauma-related PTSD compared to healthy controls. We assessed 20 female adolescent (age 12-18) single sexual trauma victims with PTSD from the Ondokuz Mayis University Department of Child and Adolescent Psychiatry between December 2013 and December 2014. PTSD symptoms were assessed using the Child Depression Inventory (CDI) and Child Posttraumatic Stress Reaction Index (CPSRI). Blood cortisol and DHEA-S were measured in 20 female adolescent sexual abuse victims with PTSD and 20 healthy adolescents after 12-h fasting using the chemiluminescence method. Compared to age-matched controls, female adolescent sexual abuse victims with PTSD had significantly lower DHEA-S levels (U = 70.00, Z = - 3.517, p = 0.01, r = 0.55). There was also a significant negative correlation between DHEA-S and CDI scores (Spearman r = - 0.522, p < 0.01). Decreased DHEA-S levels and correlation with depressive symptoms are evidence for a dysregulated HPA-axis in female adolescent single sexual trauma victims with PTSD. Further research is now recommended with large patient groups in order to maximize generalizations.

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development.

PubMed

Nguyen, Tuong-Vi; Wu, Mia; Lew, Jimin; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Fonov, Vladimir S; Collins, D Louis; Campbell, Benjamin C; Booij, Linda; Herba, Catherine; Monnier, Patricia; Ducharme, Simon; McCracken, James T

2017-12-01

Existing studies suggest that dehydroepiandrosterone (DHEA) may be important for human brain development and cognition. For example, molecular studies have hinted at the critical role of DHEA in enhancing brain plasticity. Studies of human brain development also support the notion that DHEA is involved in preserving cortical plasticity. Further, some, though not all, studies show that DHEA administration may lead to improvements in working memory in adults. Yet these findings remain limited by an incomplete understanding of the specific neuroanatomical mechanisms through which DHEA may impact the CNS during development. Here we examined associations between DHEA, cortico-hippocampal structural covariance, and working memory (216 participants [female=123], age range 6-22 years old, mean age: 13.6 +/-3.6 years, each followed for a maximum of 3 visits over the course of 4 years). In addition to administering performance-based, spatial working memory tests to these children, we also collected ecological, parent ratings of working memory in everyday situations. We found that increasingly higher DHEA levels were associated with a shift toward positive insular-hippocampal and occipito-hippocampal structural covariance. In turn, DHEA-related insular-hippocampal covariance was associated with lower spatial working memory but higher overall working memory as measured by the ecological parent ratings. Taken together with previous research, these results support the hypothesis that DHEA may optimize cortical functions related to general attentional and working memory processes, but impair the development of bottom-up, hippocampal-to-cortical connections, resulting in impaired encoding of spatial cues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adrenarche in bonobos (Pan paniscus): evidence from ontogenetic changes in urinary dehydroepiandrosterone-sulfate levels.

PubMed

Behringer, Verena; Hohmann, Gottfried; Stevens, Jeroen M G; Weltring, Anja; Deschner, Tobias

2012-07-01

Adrenarche is characterized by the onset of adrenal secretions of increasing amounts of dehydroepiandrosterone-sulfate (DHEA-S). While the function of adrenarche remains a matter of speculation, evidence suggests that the morphological and physiological changes related to it are restricted to humans and closely related primates. Within the primate order, adrenarche has been described only in humans and chimpanzees, but bonobos, the sister species of chimpanzees, have not yet been studied regarding the early ontogenetic changes such as adrenarche. While bonobos and chimpanzees share many morphological and behavioral characteristics, they differ in a number of behavioral traits, and there is a growing interest in terms of the physiological differences that can be linked to species-specific patterns of social behavior. In this study, we measured urinary DHEA-S levels to determine whether bonobos experience physiological changes that are indicative of adrenarche. We measured DHEA-S in urine using ELISA and analyzed its levels in the samples from 53 bonobos aged 1-18 years. Our results show that bonobos experience an increase in DHEA-S levels after 5 years of age, which is comparable with the patterns observed in humans and chimpanzees. This indicates that bonobos do undergo adrenarche and that the timing of onset is similar to that of the two Pan species. The extraction procedures described in this report demonstrate the use of urine for monitoring ontogenetic changes in DHEA-S excretion. If applicable to other species, the technique would facilitate more research on the evolutionary origin of adrenarche and other developmental processes.

Effects of dehydroepiandrosterone in rats injected with streptozotocin during the neonatal period.

PubMed

Giroix, M H; Malaisse-Lagae, F; Portha, B; Sener, A; Malaisse, W J

1997-06-01

Control rats and diabetic animals injected with streptozotocin during the neonatal period were either maintained on a standard diet or given access to food supplemented with dehydroepiandrosterone (DHEA, 0.2%) for 11 days before sacrifice. In both control and diabetic rats, DHEA feeding augmented the activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase and cytosolic NADP-linked malate dehydrogenase in liver, but not so in either the parotid gland or pancreatic islets. DHEA lowered, in both control and diabetic rats, the ratio between D-glucose oxidation and utilization and the rate of insulin release in pancreatic islets exposed to a high concentration of D-glucose, as well as the insulin concentration and insulin/glucose ratio in plasma. These findings support the view that, in diabetes, DHEA, by increasing sensitivity to insulin, may allow islet B-cells to avoid the otherwise unfavorable consequences of chronic hyperactivity.

Solubility and transdermal permeation properties of a dehydroepiandrosterone cyclodextrin complex from hydrophilic and lipophilic vehicles.

PubMed

Ceschel, GianCarlo; Bergamante, Valentina; Maffei, Paola; Lombardi Borgia, Simone; Calabrese, Valeria; Biserni, Stefano; Ronchi, Celestino

2005-01-01

The permeation ability of a compound is due principally to its concentration in the vehicle and to its aptitude to cross the stratum corneum of the skin. In this work ex-vivo permeation studies on newly developed formulations containing dehydroepiandrosterone (DHEA) were carried out to investigate vehicles that increase drug permeation through the skin. To enhance the solubility of DHEA, its complex form with alpha-cyclodextrin was used. In addition, the two forms (pure drug and complex form) were introduced in hydrophilic (water), lipophilic (paraffin oil), and microemulsion vehicles to evaluate the synergic effect of cyclodextrins and microemulsion vehicles on solubility and permeation. From the results, DHEA solubility is notably conditioned by the type of the vehicle used: the highest solubilities (both for pure and complex drug forms) were obtained with microemulsion, followed by paraffin oil and water. Moreover, in all the studied vehicles, the c-DHEA was more soluble than DHEA. Permeation profile fluxes showed very interesting differences. That reflect the varying drug forms (pure drug and complex form), vehicles used, and drug concentrations in the vehicles. The major flux was obtained in complex of DHEA with alpha-cyclodextrins in the microemulsion vehicle. Therefore, this type of vehicle and drug form would be very useful in the development of a topical formulation containing DHEA.

Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects.

PubMed

Martina, Valentino; Benso, Andrea; Gigliardi, Valentina Ramella; Masha, Andi; Origlia, Carla; Granata, Riccarda; Ghigo, Ezio

2006-03-01

Several clinical and population-based studies suggest that dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) play a protective role against atherosclerosis and coronary artery disease in human. However, the mechanisms underlying this action are still unknown. It has recently been suggested that DHEA-S could delay atheroma formation through an increase in nitric oxide (NO) production. Twenty-four aged male subjects [age (mean +/- SEM): 65.4 +/- 0.7 year; range: 58.2-67.6 years] underwent a blinded placebo controlled study receiving DHEA (50 mg p.o. daily at bedtime) or placebo for 2 months. Platelet cyclic guanosine-monophosphate (cGMP) concentration (as marker of NO production) and serum levels of DHEA-S, DHEA, IGF-I, insulin, glucose, oestradiol (E(2)), testosterone, plasminogen activator inhibitor (PAI)-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and after the 2-month treatment with DHEA or placebo. At the baseline, all variables in the two groups were overlapping. All parameters were unchanged after treatment with placebo. Conversely, treatment with DHEA (a) increased (P < 0.001 vs. baseline) platelet cGMP (111.9 +/- 7.1 vs. 50.1 +/- 4.1 fmol/10(6) plts), DHEA-S (13.6 +/- 0.8 vs. 3.0 +/- 0.3 micromol/l), DHEA (23.6 +/- 1.7 vs. 15.3 +/- 1.4 nmol/l), testosterone (23.6 +/- 1.0 vs. 17.7 +/- 1.0 nmol/l) and E(2) (72.0 +/- 5.0 vs. 60.0 +/- 4.0 pmol/l); and (b) decreased (P < 0.05 vs. baseline) PAI-1 Ag (27.4 +/- 3.8 vs. 21.5 +/- 2.5 ng/ml) and low-density lipoprotein (LDL) cholesterol (3.4 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l). IGF-I, insulin, glucose, triglycerides, total cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and homocysteine levels were not modified by DHEA treatment. This study shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1

Corticosterone and dehydroepiandrosterone in songbird plasma and brain: effects of season and acute stress

PubMed Central

Newman, Amy E. M.; Soma, Kiran K.

2010-01-01

Prolonged increases in plasma glucocorticoids can exacerbate neurodegeneration. In rats, these neurodegenerative effects can be reduced by dehydroepiandrosterone (DHEA), an androgen precursor with anti-glucocorticoid actions. In song sparrows, season and acute restraint stress affect circulating levels of corticosterone and DHEA, and the effects of stress differ in plasma collected from the brachial and jugular veins. Jugular plasma is an indirect index of the neural steroidal milieu. Here, we directly measured corticosterone and DHEA in several brain regions and jugular plasma, and examined the effects of season and acute restraint stress (30 min) (n = 571 samples). Corticosterone levels were up to 10× lower in brain than in jugular plasma. In contrast, DHEA levels were up to 5× higher in brain than in jugular plasma and were highest in the hippocampus. Corticosterone and DHEA concentrations were strongly seasonally regulated in plasma but, surprisingly, not seasonally regulated in brain. Acute stress increased corticosterone levels in plasma and brain, except during the molt, when stress unexpectedly decreased corticosterone levels in the hippocampus. Acute stress increased DHEA levels in plasma during the molt but had no effects on DHEA levels in brain. This is the first study to measure (i) corticosterone or DHEA levels in the brain of adult songbirds and (ii) seasonal changes in corticosterone or DHEA levels in the brain of any species. These results highlight several critical differences between systemic and local steroid concentrations and the difficulty of using circulating steroid levels to infer local steroid levels within the brain. PMID:19473242

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

PubMed

Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W

2017-11-01

To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE

Effect of age, gender and exercise on salivary dehydroepiandrosterone circadian rhythm profile in human volunteers.

PubMed

Al-Turk, Walid; Al-Dujaili, Emad A S

2016-02-01

There has been a lot of effort by scientists to elucidate the multi functions of the naturally occurring hormone, dehydroepiandrosterone (DHEA). However, to plan research experiments optimally, it is important first to characterize the diurnal rhythm in healthy individuals. The aim of this research was to investigate the daily circadian rhythms of DHEA among the 2 genders, and the effect of age and exercise on salivary DHEA circadian rhythms. Volunteers (20-39 and 40-60 years) were recruited for 2 studies investigating the salivary DHEA circadian rhythm. The first study looked at the effect of gender and age on DHEA levels on 2 non-consecutive days, and the second study explored the effect of exercise on DHEA circadian rhythm in males. DHEA levels were estimated by a sensitive and specific ELISA method. The results showed a clear daily circadian rhythm in salivary DHEA in all participants groups, however the profile was flatter in the older female group. There was a significant difference between age and gender groups particularly at 8.00 h. In young males DHEA reduced from 541.1 ± 101.3 (mean ± sd) at 8.00 h to 198.9 ± 90.7 pg/mL at 18.00 h; p<0.0001, and young females from 401.6 ± 149.5 to 215.4 ± 95.3 pg/mL; p<0.001. In older males DHEA reduced from 267.5 ± 32.4 to 132.5 ± 46.7 pg/mL; p<0.001, and older females from 147.7 ± 78.1 to 89.5 ± 29.1 pg/mL; p=0.05. DHEA levels on 2 non-consecutive days showed some variations but this was not significant. Aerobic exercise has significantly increased DHEA levels at 2 time points of the day (p=0.05) in male subjects. In conclusion, our study showed a clear daily circadian rhythm in salivary DHEA in all participants was observed, but the profile was flatter in the older groups. Copyright © 2016. Published by Elsevier Inc.

Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity.

PubMed

Ben-Nathan, D; Padgett, D A; Loria, R M

1999-05-01

The protective effects of the hormones androstenediol (androstene-3beta, 17beta,-diol; AED) and dehydroepiandrosterone (5-androsten-3beta-ol-17-one; DHEA) on the pathophysiology of two lethal bacterial infections and endotoxin shock were examined. The infections included a gram-positive organism (Enterococcus faecalis) and a gram-negative organism (Pseudomonas aeruginosa). Both hormones protected mice from the lethal bacterial infections and from lipopolysaccharide (LPS) challenge. Treatment of animals lethally infected with P. aeruginosa with DHEA resulted in a 43% protection whereas treatment with AED gave a 67% protection. Both hormones also protected completely animals infected with an LD50 dose of E. faecalis. Similarly, the 88% mortality rate seen in LPS challenge was reduced to 17% and 8.5%, by treatment with DHEA and AED, respectively. The protective influences of both steroids were shown not to be directly antibacterial, but primarily an indirect antitoxin reaction. DHEA appears to mediate its protective effect by a mechanism that blocks the toxin-induced production of pathophysiological levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1. AED usually had greater protective effects than DHEA; however, the AED effect was independent of TNF-alpha suppression, both in vivo and in vitro. The data suggest that both DHEA and AED may have a role in the neuro-endocrine regulation of antibacterial immune resistance.

Acute Effects of Oral Dehydroepiandrosterone on Counterregulatory Responses During Repeated Hypoglycemia in Healthy Humans

PubMed Central

Mikeladze, Maia; Hedrington, Maka S.; Joy, Nino; Tate, Donna B.; Younk, Lisa M.; Davis, Ian

2016-01-01

We tested the hypothesis that acute administration of oral dehydroepiandrosterone (DHEA) during episodes of repeated hypoglycemia can prevent the development of hypoglycemia-associated neuroendocrine and autonomic failure in healthy humans. Twenty-seven individuals (16 men, 11 women) participated in two separate randomized, single-blind, 2-day protocols. Day 1 consisted of morning and afternoon 2-h hypoglycemic clamps (2.9 mmol/L) with 800 mg of DHEA or placebo administered before each clamp. Day 2 consisted of a single 2-h hypoglycemic clamp (2.9 mmol/L) following either DHEA (1,600 mg) or placebo. A 3-tritiated glucose was used to determine glucose kinetics during hypoglycemia on day 2. Antecedent hypoglycemia with placebo resulted in significant reductions of epinephrine, norepinephrine, glucagon, growth hormone, cortisol, endogenous glucose production, and lipolytic and symptom responses. During hypoglycemia on day 2, DHEA prevented blunting of all neuroendocrine, autonomic nervous system (ANS), metabolic, and symptom counterregulatory responses following hypoglycemia on day 1. In summary, DHEA can acutely preserve a wide range of key neuroendocrine, ANS, and metabolic counterregulatory homeostatic responses during repeated hypoglycemia. We conclude that DHEA may have acute effects to protect against hypoglycemia-associated neuroendocrine and autonomic failure in healthy humans. PMID:27486235

Concurrent change in dehydroepiandrosterone sulfate and functional performance in the oldest old: results from the Cardiovascular Health Study All Stars study.

PubMed

Sanders, J L; Cappola, A R; Arnold, A M; Boudreau, R M; Chaves, P H; Robbins, J; Cushman, M; Newman, A B

2010-09-01

The correlation between dehydroepiandrosterone sulfate (DHEAS) decline and age led to the hypothesis that DHEAS might be a marker of primary aging, though conflicting data from observational studies of mortality do not support this. We evaluated concurrent DHEAS and functional decline in a very old cohort to test if DHEAS change tracks with functional change during aging. DHEAS and functional performance (gait speed, grip strength, Modified Mini-Mental State Examination [3MSE] score, and digit symbol substitution test [DSST] score) were measured in 1996-1997 and 2005-2006 in 989 participants in the Cardiovascular Health Study All Stars study (mean age 85.2 years in 2005-2006, 63.5% women and 16.5% African American). We used multivariable linear regression to test the association of DHEAS decline with functional decline. After adjustment, each standard deviation decrease in DHEAS was associated with greater declines in gait speed (0.12 m/s, p = .01), grip strength (0.09 kg, p = .03), 3MSE score (0.13 points, p < .001), and DSST score (0.14 points, p = .001) in women only. Additional adjustment for baseline DHEAS attenuated the association with grip strength but did not alter other estimates appreciably, and baseline DHEAS was unassociated with functional decline. In this cohort of very old individuals, DHEAS decline tracked with declines in gait speed, 3MSE score, and DSST score, but not grip strength, in women independent of baseline DHEAS level. DHEAS decline might be a marker for age-associated performance decline, but its relevance is specific to women.

The use of coenzyme Q10 and DHEA during IUI and IVF cycles in patients with decreased ovarian reserve.

PubMed

Gat, Itai; Blanco Mejia, Sonia; Balakier, Hanna; Librach, Clifford L; Claessens, Anne; Ryan, Edward A J

2016-07-01

The objective of this study is to compare the combination of dehydroepiandrosterone (DHEA) and coenzyme Q10 (CoQ10) (D + C) with DHEA alone (D) in intrauterine insemination (IUI) and in vitro fertilization (IVF) cycles among patients with decreased ovarian reserve. We retrospectively extracted data from patients charts treated by DHEA with/without CoQ10 during IUI or IVF between February 2006 and June 2014. Prestimulation parameters included age, BMI, day 3 FSH and antral follicular count (AFC). Ovarian response parameters included total gonadotropins dosage, peak serum estradiol, number of follicles > 16 mm and fertilization rate. Clinical outcomes included clinical and ongoing pregnancy rates. Three hundred and thirty IUI cycles involved D + C compared with 467 cycles of D; 78 IVF cycles involved D + C and 175 D. In both IUI and IVF, AFC was higher with D + C compared with D (7.4 ± 5.7 versus 5.9 ± 4.7, 8.2 ± 6.3 versus 5.2 ± 5, respectively, p < 0.05). D + C resulted in a more follicles > 16 mm during IUI cycles (3.3 ± 2.3 versus 2.9 ± 2.2, respectively, p = 0.01), while lower mean total gonadotropin dosage was administered after D + C supplementation compared with D (3414 ± 1141 IUs versus 3877 ± 1143 IUs respectively, p = 0.032) in IVF cycles. Pregnancy and delivery rates were similar for both IUI and IVF. D + C significantly increases AFC and improves ovarian responsiveness during IUI and IVF without a difference in clinical outcome.

Leukocyte Telomere Length and Serum Levels of High-Molecular-Weight Adiponectin and Dehydroepiandrosterone-Sulfate Could Reflect Distinct Aspects of Longevity in Japanese Centenarians.

PubMed

Aoki, Yuji; Aoki, Masato; Yamada, Kazuya

2017-01-01

Leukocyte telomere length and serum levels of high-molecular-weight adiponectin and dehydroepiandrosterone-sulfate (DHEA-S) were assessed in association with nutrition and performance status (PS) in Japanese centenarians. Twenty-three centenarians (five men, 18 women) were classified according to their PS 1 (nearly fully ambulatory, n = 2), 2 (in bed less than 50% of daytime, n = 10), 3 (in bed greater than 50%, n = 6), and 4 (completely bedridden, n = 5). Leukocyte telomere length was determined by the hybridization protection assay, and the adiponectin and DHEA-S levels were measured by chemiluminescent enzyme immunoassay. Among variables of PS, body mass index (BMI), albumin, adiponectin, DHEA-S, and telomere length, there were significant correlations between PS and albumin ( r = -.694, p < .01), between telomere length and BMI ( r = .522, p < .05), between adiponectin and BMI ( r = -.574, p < .01), and between DHEA-S and albumin ( r = .530, p < .01). When excluding two cancer-bearing centenarians with short telomere, telomere length significantly correlated with PS ( r = -.632, p < .01). It was indicated that the short leukocyte telomere was associated with poor PS and cancer development and that the adiponectin or DHEA-S was associated with adiposity or nutritional status. Despite a small number of subjects, these biomarkers seemed to reflect distinct aspects of longevity in Japanese centenarians.

Serum cortisol and dehydroepiandrosterone-sulfate levels after balneotherapy and physical therapy in patients with fibromyalgia

PubMed Central

Semiz, Esra A.; Hizmetli, Sami; Semiz, Murat; Karadağ, Ahmet; Adalı, Merve; Tuncay, Mehmet S.; Alim, Bulent; Hayta, Emrullah; Uslu, Ali U.

2016-01-01

Objectives: To investigated serum cortisol and serum dehydroepiandrosterone-sulphate (DHEA-S) levels between fibromyalgia (FMS) patients and a control group, and the effect of balneotherapy (BT) on these hormones. Methods: Seventy-two patients with FMS and 39 healthy volunteers were included in the study. This prospective and cross-sectional study was carried out in the Medical Faculty, Physical Medicine and Rehabilitation Clinic, Cumhuriyet University, Cumhuriyet, Turkey between June 2012 and June 2013. Patients were divided into 2 groups. There were 40 patients in the first group, consisting of BT and physical therapy (PT) administered patients. There were 32 FMS patients in the second group who were only administered PT. Thirty-nine healthy volunteers were enrolled as a control group. Result: Cortisol was observed to be lower in FMS patients compared with the controls (10.10±4.08 μg/dL and 11.78±3.6 μg/dL; p=0.033). Serum DHEA-S level was observed to be lower in FMS patients compared with the controls (89.93±53.96 μg/dL and 143.15±107.92 μg/dL; p=0.015). Average serum cortisol levels of patients receiving BT were determined to be 9.95±3.20 μg/dL before treatment and 9.06±3.77μg/dL after treatment; while average serum DHEA-S levels were 77.60±48.05 μg/dL before treatment, and 76.84±48.71 μg/dL after treatment. No significant changes were determined in serum cortisol and DHEA-S levels when measured again after BT and PT. Conclusion: Low levels of serum cortisol and DHEA-S were suggested to be associated with the physiopathology of FMS. PMID:27146618

Serum cortisol and dehydroepiandrosterone-sulfate levels after balneotherapy and physical therapy in patients with fibromyalgia.

PubMed

Semiz, Esra A; Hizmetli, Sami; Semiz, Murat; Karadağ, Ahmet; Adalı, Merve; Tuncay, Mehmet S; Alim, Bulent; Hayta, Emrullah; Uslu, Ali U

2016-05-01

To investigated serum cortisol and serum dehydroepiandrosterone-sulphate (DHEA-S) levels between fibromyalgia (FMS) patients and a control group, and the effect of balneotherapy (BT) on these hormones.   Seventy-two patients with FMS and 39 healthy volunteers were included in the study. This prospective and cross-sectional study was carried out in the Medical Faculty, Physical Medicine and Rehabilitation Clinic, Cumhuriyet University, Cumhuriyet, Turkey between June 2012 and June 2013. Patients were divided into 2 groups. There were 40 patients in the first group, consisting of BT and physical therapy (PT) administered patients. There were 32 FMS patients in the second group who were only administered PT. Thirty-nine healthy volunteers were enrolled as a control group.   Cortisol was observed to be lower in FMS patients compared with the controls  (10.10±4.08 µg/dL and 11.78±3.6 µg/dL; p=0.033). Serum DHEA-S level was observed to be lower in FMS patients compared with the controls (89.93±53.96 µg/dL and 143.15±107.92 µg/dL; p=0.015). Average serum cortisol levels of patients receiving BT were determined to be 9.95±3.20 µg/dL before treatment and 9.06±3.77µg/dL after treatment; while average serum DHEA-S levels were 77.60±48.05 µg/dL before treatment, and 76.84±48.71 µg/dL after treatment. No significant changes were determined in serum cortisol and DHEA-S levels when measured again after BT and PT.   Low levels of serum cortisol and DHEA-S were suggested to be associated with the physiopathology of FMS.

Is there a relationship between cardiovascular risk factors and dehydroepiandrosterone sulfate levels in childhood obesity?

PubMed

Akyürek, Nesibe; Atabek, Mehmet Emre; Eklioglu, Beray Selver; Alp, Hayrullah

2015-05-01

In this study, parameters of metabolic syndrome and dehydroepiandrosterone sulfate (DHEAS) levels in obese children and adolescents were evaluated and the associations between these factors were analyzed. One hundred obese and 40 healthy children/adolescents were included in the study. Pubertal stages, anthropometric and blood pressure measurements were recorded. Levels of fasting serum lipids, glucose, insulin, and DHEAS, and liver function tests were determined. Carotid intima-media thickness (CIMT) was measured using two-dimensional echocardiography. Steatorrhoeic hepatosis was evaluated using abdominal ultrasonography in the obese group. Mean body weight, body mass index, waist, hip circumference, waist/hip ratio, homeostatic model assessment of insulin resistance, triglycerides, high-density lipoprotein cholesterol, alanine transferase, DHEAS, and CIMT values were significantly higher in the obese group than in the controls. DHEAS levels were found to be positively correlated with waist circumference, waist/hip ratio, and CIMT. Early determination of metabolic and cardiac dysfunction in obese children is important for the prevention of future complications. Since in this study we found a strong association between DHEAS levels and obesity-related metabolic and cardiovascular risk factors, we believe that this may lead to increased interest in further studies of DHEAS in the search for new treatment approaches.

Follicular fluid dehydroepiandrosterone sulfate is a credible marker of oocyte maturity and pregnancy outcome in conventional in vitro fertilization cycles.

PubMed

Chimote, Natachandra M; Nath, Nirmalendu M; Chimote, Nishad N; Chimote, Bindu N

2015-01-01

To investigate if the level of dehydroepiandrosterone sulfate (DHEA-s) in follicular fluid (FF) influences the competence of oocytes to fertilize, develop to the blastocyst stage, and produce a viable pregnancy in conventional in vitro fertilization (IVF) cycles. Prospective study of age-matched, nonpolycystic ovary syndrome (PCOS) women undergoing antagonist stimulation protocol involving conventional insemination and day 5 blastocyst transfer. FF levels of DHEA-s and E2 were measured by a radio-immuno-assay method using diagnostic kits. Fertilization rate, embryo development to the blastocyst stage and live birth rate were main outcome measures. Cycles were divided into pregnant/nonpregnant groups and also into low/medium/high FF DHEA-s groups. Statistical analysis was done by GraphPad Prism V software. FF DHEA-s levels were significantly higher in pregnant (n = 111) compared to nonpregnant (n = 381) group (1599 ± 77.45 vs. 1372 ± 40.47 ng/ml; P = 0.01). High (n = 134) FF DHEA-s group had significantly higher percentage of metaphase II (MII) oocytes (91.5 vs. 85.54 vs. 79.44%, P < 0.0001), fertilization rate (78.86 vs. 74.16 vs. 71.26%, P < 0.0001), cleavage rate (83.67 vs. 69.1 vs. 66.17%, P = 0.0002), blastocyst formation rate (37.15 vs. 33.01 vs. 26.95%, P < 0.0001), and live birth rate (29.85 vs. 22.22 vs. 14.78%, P = 0.017) compared to medium (n = 243) and low (n = 115) FF DHEA-s groups, respectively despite comparable number of oocytes retrieved and number of blastocysts transferred. FF DHEA-s levels correlated significantly with the attainment of MII oocytes (Pearson r = 0.41) and fertilization rates (Pearson r = 0.35). FF DHEA-s level influences the oocyte maturation process and is predictive of fertilization, embryo development to the blastocyst stage and live birth rates in non-PCOS women undergoing conventional IVF cycles.

Atorvastatin therapy decreases androstenedione and dehydroepiandrosterone sulphate concentrations in patients with polycystic ovary syndrome: randomized controlled study.

PubMed

Sathyapalan, Thozhukat; Smith, Karen A; Coady, Anne-Marie; Kilpatrick, Eric S; Atkin, Stephen L

2012-01-01

Hyperandrogenaemia in polycystic ovary syndrome (PCOS) represents a composite of raised serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS). In patients with PCOS, testosterone and androstenedione are primarily derived from the ovaries and DHEAS is a metabolite predominantly from the adrenals. It has been shown that atorvastatin reduces testosterone concentrations in patients with PCOS. The objective was to study the effect of atorvastatin on serum androstenedione and DHEAS concentrations in patients with PCOS. A randomized, double-blind, placebo-controlled study was performed. Forty medication-naive patients with PCOs were randomized to either atorvastatin 20mg daily or placebo for three months. Subsequently, a three-month extension study for all patients was undertaken with metformin 1500 mg daily. The main outcome measures were change in androstenedione and DHEAS concentrations. The mean (SD) baseline androstenedione (5.7 [0.8] versus 5.6 [1.3] nmol/L; P = 0.69) and DHEAS (7.1 [1.0] versus 7.2 [1.2] μmol/L; P = 0.72) concentrations were comparable between two groups. There was a significant reduction of androstenedione (5.7 [0.8] versus 4.7 [0.7] nmol/L; P = 0.03) and DHEAS (7.1 [1.0] versus 6.0 [0.9] μmol/L; P = 0.02) with three months of atorvastatin while there were no significant changes with placebo. Three months' treatment with metformin maintained the reduction of androstenedione and DHEAS concentrations with atorvastatin compared with baseline. There were no changes in either DHEAS or androstenedione concentrations in the initial placebo group after 12 weeks of metformin. Twelve weeks of atorvastatin significantly reduced both DHEAS and androstenedione contributing to the total reduction of androgen concentrations and indicating that the reduction of the hyperandrogenaemia could be partly due to the action of atorvastatin at both the ovary and the adrenal gland in PCOS.

Effects of menstrual cycle, oral contraception, and training on exercise-induced changes in circulating DHEA-sulphate and testosterone in young women.

PubMed

Enea, C; Boisseau, N; Ottavy, M; Mulliez, J; Millet, C; Ingrand, I; Diaz, V; Dugué, B

2009-06-01

The objective of this study was to ascertain the effects of menstrual cycle, oral contraception, and training status on the exercise-induced changes in circulating DHEA-sulphate and testosterone in young women. Twenty-eight healthy women were assigned to an untrained group (n = 16) or a trained group (n = 12) depending on their training background. The untrained group was composed of nine oral contraceptive users (OC+) and seven eumenorrheic women (OC-). The trained group was composed of OC+ subjects only. All the OC+ subjects were taking the same low-dose oral contraception. Three laboratory sessions were organised in a randomised order: a prolonged exercise test until exhaustion, a short-term exhaustive exercise test, and a control session. Blood specimens were collected before, during and after the exercise tests and at the same time of the day during the control session. Basal circulating testosterone was significantly lower in trained as compared to untrained subjects. In all subjects, the prolonged exhaustive exercise induced a significant increase in circulating DHEA-s and testosterone. The short-term exercise induced a significant increase in circulating DHEA-s in untrained eumenorrheic and in trained OC users only. Menstrual phases in OC- did not influence the responses. It was found that exhaustive physical exercise induced an increase in circulating DHEA-s and testosterone in young women. Oral contraception may limit short-term exercise-induced changes.

Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells.

PubMed

Teng, Yun; Radde, Brandie N; Litchfield, Lacey M; Ivanova, Margarita M; Prough, Russell A; Clark, Barbara J; Doll, Mark A; Hein, David W; Klinge, Carolyn M

2015-06-19

Little is known about the regulation of the oncomiR miR-21 in liver. Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G-protein-coupled receptor and as a precursor for steroids that activate nuclear receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR-21) transcription and mature miR-21 expression in HepG2 cells in a biphasic manner with an initial peak at 1 h followed by a second, sustained response from 3-12 h. DHEA also increased miR-21 in primary human hepatocytes and Hep3B cells. siRNA, antibody, and inhibitor studies suggest that the rapid DHEA-mediated increase in miR-21 involves a G-protein-coupled estrogen receptor (GPER/GPR30), estrogen receptor α-36 (ERα36), epidermal growth factor receptor-dependent, pertussis toxin-sensitive pathway requiring activation of c-Src, ERK1/2, and PI3K. GPER antagonist G-15 attenuated DHEA- and BSA-conjugated DHEA-stimulated pri-miR-21 transcription. Like DHEA, GPER agonists G-1 and fulvestrant increased pri-miR-21 in a GPER- and ERα36-dependent manner. DHEA, like G-1, increased GPER and ERα36 mRNA and protein levels. DHEA increased ERK1/2 and c-Src phosphorylation in a GPER-responsive manner. DHEA increased c-Jun, but not c-Fos, protein expression after 2 h. DHEA increased androgen receptor, c-Fos, and c-Jun recruitment to the miR-21 promoter. These results suggest that physiological concentrations of DHEA activate a GPER intracellular signaling cascade that increases pri-miR-21 transcription mediated at least in part by AP-1 and androgen receptor miR-21 promoter interaction. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells*

PubMed Central

Teng, Yun; Radde, Brandie N.; Litchfield, Lacey M.; Ivanova, Margarita M.; Prough, Russell A.; Clark, Barbara J.; Doll, Mark A.; Hein, David W.; Klinge, Carolyn M.

2015-01-01

Little is known about the regulation of the oncomiR miR-21 in liver. Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G-protein-coupled receptor and as a precursor for steroids that activate nuclear receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR-21) transcription and mature miR-21 expression in HepG2 cells in a biphasic manner with an initial peak at 1 h followed by a second, sustained response from 3–12 h. DHEA also increased miR-21 in primary human hepatocytes and Hep3B cells. siRNA, antibody, and inhibitor studies suggest that the rapid DHEA-mediated increase in miR-21 involves a G-protein-coupled estrogen receptor (GPER/GPR30), estrogen receptor α-36 (ERα36), epidermal growth factor receptor-dependent, pertussis toxin-sensitive pathway requiring activation of c-Src, ERK1/2, and PI3K. GPER antagonist G-15 attenuated DHEA- and BSA-conjugated DHEA-stimulated pri-miR-21 transcription. Like DHEA, GPER agonists G-1 and fulvestrant increased pri-miR-21 in a GPER- and ERα36-dependent manner. DHEA, like G-1, increased GPER and ERα36 mRNA and protein levels. DHEA increased ERK1/2 and c-Src phosphorylation in a GPER-responsive manner. DHEA increased c-Jun, but not c-Fos, protein expression after 2 h. DHEA increased androgen receptor, c-Fos, and c-Jun recruitment to the miR-21 promoter. These results suggest that physiological concentrations of DHEA activate a GPER intracellular signaling cascade that increases pri-miR-21 transcription mediated at least in part by AP-1 and androgen receptor miR-21 promoter interaction. PMID:25969534

Interactive effects of dehydroepiandrosterone and testosterone on cortical thickness during early brain development.

PubMed

Nguyen, Tuong-Vi; McCracken, James T; Ducharme, Simon; Cropp, Brett F; Botteron, Kelly N; Evans, Alan C; Karama, Sherif

2013-06-26

Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.

Dehydroepiandrosterone administration counteracts oxidative imbalance and advanced glycation end product formation in type 2 diabetic patients.

PubMed

Brignardello, Enrico; Runzo, Cristina; Aragno, Manuela; Catalano, Maria Graziella; Cassader, Maurizio; Perin, Paolo Cavallo; Boccuzzi, Giuseppe

2007-11-01

Dehydroepiandrosterone (DHEA) has been shown to prevent oxidative stress in several in vivo and in vitro models. This study aimed to evaluate the effects of DHEA administration on oxidative stress, pentosidine concentration, and tumor necrosis factor (TNF)-alpha/TNF-alpha receptor system activity in patients with type 2 diabetes. Twenty patients were enrolled in the study and randomly assigned to the DHEA (n = 10) or placebo (n = 10) group. Twenty healthy sex- and age-matched subjects with normal glucose levels served as control subjects. DHEA was given as a single daily dose of 50 mg for 12 weeks. Oxidative stress parameters were significantly higher in diabetic patients versus control subjects. Pentosidine levels, as well as soluble TNF receptor (sTNF-R)I and sTNF-RII, were also higher in diabetic patients. After DHEA, plasma levels of reactive oxygen species and hydroxynonenal dropped by 53 and 47%, respectively, whereas the nonenzymatic antioxidants glutathione and vitamin E increased (+38 and +76%, respectively). The same changes in oxidative parameters were detected in peripheral blood mononuclear cells (PBMCs). DHEA treatment also induced a marked decrease of pentosidine plasma concentration in diabetic patients (-50%). Moreover, the TNF-alpha/TNF-alpha receptor system was shown to be less activated after DHEA treatment, in both plasma and PBMCs. Data indicate that DHEA treatment ameliorates the oxidative imbalance induced by hyperglycemia, downregulates the TNF-alpha/TNF-alpha receptor system, and prevents advanced glycation end product formation, suggesting a beneficial effect on the onset and/or progression of chronic complications in type 2 diabetic patients.

Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.

PubMed

Kuebler, J F; Jarrar, D; Wang, P; Bland, K I; Chaudry, I H

2001-05-15

Recent studies have shown that administration of the sex steroid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has salutary effects on the depressed cardiovascular and immunological functions under those conditions. Since the effects of sex steroids are gender specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Ovariectomy was performed in female Sprague-Dawley rats 14 days prior to the experiments. The animals then underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was followed by fluid resuscitation (Ringer's lactate over 60 min) and administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resuscitation. At 24 h after resuscitation hepatocellular function, i.e., clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were also assayed. Vehicle-treated rats had significantly reduced hepatocellular function, increased ALT activity, and decreased levels of 17beta-estradiol following trauma-hemorrhage compared to sham-operated animals (P < 0.05, ANOVA and Student-Newman-Keuls test). In animals receiving DHEA following trauma-hemorrhage, hepatocellular function and ALT activity were similar to those of shams. However, administration of DHEA did not influence the plasma levels of 17beta-estradiol. Administration of DHEA following trauma-hemorrhage restored hepatocellular function and reduced hepatic damage that was observed in ovariectomized female rats under such conditions. This salutary effect of DHEA did not appear to be due to elevated levels of plasma 17beta-estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in ovariectomized and

Alterations of hair cortisol and dehydroepiandrosterone in mother-infant-dyads with maternal childhood maltreatment.

PubMed

Schury, K; Koenig, A M; Isele, D; Hulbert, A L; Krause, S; Umlauft, M; Kolassa, S; Ziegenhain, U; Karabatsiakis, A; Reister, F; Guendel, H; Fegert, J M; Kolassa, I-T

2017-06-06

Child maltreatment (CM) has severe effects on psychological and physical health. The hypothalamic-pituitary-adrenal (HPA) axis, the major stress system of the body, is dysregulated after CM. The analysis of cortisol and dehydroepiandrosterone (DHEA) in scalp hair presents a new and promising methodological approach to assess chronic HPA axis activity. This study investigated the effects of CM on HPA axis activity in the last trimester of pregnancy by measuring the two important signaling molecules, cortisol and DHEA in hair, shortly after parturition. In addition, we explored potential effects of maternal CM on her offspring's endocrine milieu during pregnancy by measuring cortisol and DHEA in newborns' hair. CM was assessed with the Childhood Trauma Questionnaire (CTQ). Cortisol and DHEA were measured in hair samples of 94 mothers and 30 newborns, collected within six days after delivery. Associations of maternal CM on her own and her newborn's cortisol as well as DHEA concentrations in hair were analyzed with heteroscedastic regression models. Higher CM was associated with significantly higher DHEA levels, but not cortisol concentrations in maternal hair. Moreover, maternal CM was positively, but only as a non-significant trend, associated with higher DHEA levels in the newborns' hair. Results suggest that the steroid milieu of the mother, at least on the level of DHEA, is altered after CM, possibly leading to non-genomic transgenerational effects on the developing fetus in utero. Indeed, we observed on an explorative level first hints that the endocrine milieu for the developing child might be altered in CM mothers. These results need extension and replication in future studies. The measurement of hair steroids in mothers and their newborns is promising, but more research is needed to better understand the effects of a maternal history of CM on the developing fetus.

Dehydroepiandrosterone reduces accumulation of lipid droplets in primary chicken hepatocytes by biotransformation mediated via the cAMP/PKA-ERK1/2 signaling pathway.

PubMed

Li, Longlong; Ge, Chongyang; Wang, Dian; Yu, Lei; Zhao, Jinlong; Ma, Haitian

2018-06-01

Dehydroepiandrosterone (DHEA) is commonly used as a nutritional supplement to control fat deposition, but the mechanism of this action is poorly understood. In this study, we demonstrated that DHEA increased phosphorylation of AMP-activated protein kinase (p-AMPK). Elevated p-AMPK levels resulted in reduced expression of sterol regulatory element binding protein-1c, acetyl CoA carboxylase, fatty acid synthase and enhanced expression of peroxisome proliferators-activated receptor α and carnitine palmitoyl transferase-I, ultimately leading to the reduction of lipid droplet accumulation in primary chicken hepatocytes. We found that DHEA activates the cyclic adenosine 3', 5'-monophosphate/protein kinase A - extracellular signal-regulated kinase 1/2 (cAMP/PKA-ERK1/2) signaling pathway, which regulates the conversion of DHEA into testosterone and estradiol by increasing the 17β-hydroxysteroid dehydrogenase and aromatase protein expression. Importantly, the fat-reducing effects of DHEA are more closely associated with the conversion of DHEA into estradiol than with the action of DHEA itself as an active biomolecule, or to its alternative metabolite, testosterone. Taken together, our results indicate that DHEA is converted into active hormones through activation of the cAMP/PKA-ERK1/2 signaling pathway; the fat-reducing effects of DHEA are achieved through its conversion into estradiol, not testosterone, and not through direct action of DHEA itself, which led to the activation of the p-AMPK in primary chicken hepatocytes. These data provide novel insight into the mechanisms underlying the action of DHEA in preventing fat deposition, and suggest potential applications for DHEA treatment to control fat deposition or as an agent to treat disorders related to lipid metabolism in animals and humans. Copyright © 2018 Elsevier B.V. All rights reserved.

Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor.

PubMed

Straub, Rainer H; Lehle, Karin; Herfarth, Hans; Weber, Markus; Falk, Werner; Preuner, Jurgen; Scholmerich, Jurgen

2002-03-01

Serum levels of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) are low in chronic inflammatory diseases, although the reasons are unexplained. Furthermore, the behaviour of serum levels of these hormones during an acute inflammatory stressful disease state is not well known. In this study in patients with an acute inflammatory stressful disease state (13 patients undergoing cardiothoracic surgery) and patients with chronic inflammation (61 patients with inflammatory bowel diseases (IBD)) vs. 120 controls, we aimed to investigate adrenal hormone shifts looking at serum levels of DHEA in relation to other adrenal hormones. Furthermore, we tested the predictive role of serum tumour necrosis factor (TNF) and interleukin-6 (IL-6) for a change of serum levels of DHEA in relation to other adrenal hormones. The molar ratio of serum levels of DHEA/androstenedione (ASD) was increased in patients with an acute inflammatory stressful disease state and was decreased in patients with chronic inflammation. The molar ratio of serum levels of DHEAS/DHEA was reduced during an acute inflammatory stressful disease state and was increased in patients with chronic inflammation. A multiple linear regression analysis revealed that elevated serum levels of TNF were associated with a high ratio of serum levels of DHEA/ASD in all groups (for IL-6 in patients with an acute inflammatory stressful disease state only), and, similarly, elevated serum levels of TNF were associated with a high ratio of serum levels of DHEAS/DHEA only in IBD (for IL-6 only in healthy subjects). This study indicates that changes of serum levels of DHEA in relation to serum levels of other adrenal hormones are completely different in patients with an acute inflammatory stressful disease state compared with patients with chronic inflammation. The decrease of serum levels of DHEAS and DHEA is typical for chronic inflammation and TNF and IL-6 play a predictive role for these changes.

Regulation of the immune response by dehydroepiandrosterone and its metabolites.

PubMed

Loria, R M; Padgett, D A; Huynh, P N

1996-09-01

Dehydroepiandrosterone (5-androsten-3 beta-ol-17-one, DHEA) has been shown to protect mice from a variety of lethal infections. This includes, but is not limited to, infection with viruses (herpes virus type 2, coxsackie virus B4 (CB4)), bacteria (Enterococcus faecalis, Pseudomonas aeruginosa), and a parasite (Cryptosporidium parvum). We have previously reported that androstenediol (5-androstene-3 beta, 17 beta-diol, AED), derived from DHEA, is at least 100 x more effective in up-regulating systemic resistance against CB4 infection than its precursor. Furthermore, androstenetriol (5-androstene-3 beta,7 beta, 17 beta-triol, AET) which is formed by 7 beta hydroxylation of AED, was more effective against CB4 infection than its precursor, AED. Neither steroid, however, has shown any significant direct antiviral effects. The in vitro influences of DHEA, AED and AET on a mitogen-induced mixed splenocyte proliferation assay were determined. The results showed that DHEA suppressed the proliferation of concanavalin A (ConA)- or lipopolysaccharide-activated cultures in a dose-dependent manner. AED had little influence on the activation response. However, AET potentiated the response to both mitogens significantly above the control level. The regulation of interleukin (IL)-2 and IL-3 secretion from ConA-activated lymphocytes was analogous to these observations. These functions were depressed by DHEA, unaffected by AED, and potently increased by AET. Moreover, the classic immunosuppressive effects of hydrocortisone on ConA-induced lymphocyte proliferation, as well as IL-2 and IL-3 production, were unaffected by co-culture with DHEA and only minimally counteracted by AED. In contrast. AET significantly counteracted the effect of hydrocortisone when co-cultured together. These data show that while DHEA, AED and AET each function in a similar manner in vivo, in vitro their effects are dramatically different from one another with only AET potentiating the cellular response by

Dehydroepiandrosterone replacement in patients with Addison's disease has a bimodal effect on regulatory (CD4+CD25hi and CD4+FoxP3+) T cells.

PubMed

Coles, Alasdair J; Thompson, Sara; Cox, Amanda L; Curran, Suzanne; Gurnell, Elli M; Chatterjee, V Krishna

2005-12-01

Oral replacement of the near-total deficiency of dehydroepiandrosterone (DHEA) in patients with Addison's disease (adrenal insufficiency) enhances mood and well-being and reduces fatigue. We studied the immunological effects of 12 wk of oral DHEA treatment in ten patients with Addison's disease receiving their normal mineralo- and glucocorticoid hormone replacement. We found that baseline circulating regulatory T cells were reduced in Addison's disease patients compared to controls, a hitherto unrecognised defect in this disorder. Oral DHEA treatment had a bimodal effect on naturally occurring regulatory (CD4+CD25hiFoxP3+) T cells and lymphocyte FoxP3 expression. Oral DHEA replacement restored normal levels of regulatory T cells and led to increased FoxP3 expression. These effects were probably responsible for a suppression of constitutive cytokine expression following DHEA withdrawal. In contrast, oral DHEA treatment led to reduced FoxP3 expression induced by TCR engagement and so augmented the cytokine response, but without a bias towards the Th1 or Th2 phenotype. NK and NKT cell numbers fell during DHEA treatment, and homeostatic lymphocyte proliferation was increased. We conclude that DHEA replacement in Addison's disease has significant immunomodulatory properties and propose that it has a greater impact on the human immune system than would be expected from its classification as a dietary supplement.

Prognostic Value of Dehydroepiandrosterone Sulfate for Patients With Cardiovascular Disease: A Systematic Review and Meta-Analysis.

PubMed

Wu, Ting-Ting; Chen, Yuan; Zhou, Yun; Adi, Dilare; Zheng, Ying-Ying; Liu, Fen; Ma, Yi-Tong; Xie, Xiang

2017-05-05

The aim of the present study was to estimate the impact of dehydroepiandrosterone sulfate (DHEAS) on the prognosis of patients with cardiovascular disease by performing a systematic review and meta-analysis. The Embase, PubMed, Web of Science, CNKI, and WanFang databases were searched up to September 5, 2016, to identify eligible studies. The quality of each study was assessed using the Newcastle-Ottawa Scale. The association between DHEAS, either on admission or at discharge, and cardiovascular disease outcomes were reviewed. The overall risk ratio for the effect of DHEAS on all-cause mortality and fatal and nonfatal cardiovascular events was pooled using a fixed-effects or a random-effects model. The publication bias was evaluated using funnel plots. Twenty-five studies were included for systematic review. The follow-up duration ranged from 1 to 19 years. Eighteen studies were included in the meta-analysis. We found that lower DHEAS levels indicated a significant increased risk for all-cause mortality (risk ratio, 1.47; 95% CI, 1.38-1.56 [ P <0.00001]), fatal cardiovascular event (risk ratio, 1.58; 95% CI, 1.30-1.91 [ P <0.00001]), and nonfatal cardiovascular event (risk ratio, 1.42; 95% CI, 1.24-1.62 [ P <0.0001]) in patients with cardiovascular disease. Patients with cardiovascular disease who have lower DHEAS levels may have poorer prognosis than those with higher DHEAS levels. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Chemoprevention of rat prostate carcinogenesis by dietary 16alpha-fluoro-5-androsten-17-one (fluasterone), a minimally androgenic analog of dehydroepiandrosterone.

PubMed

McCormick, David L; Johnson, William D; Kozub, Nicole M; Rao, K V N; Lubet, Ronald A; Steele, Vernon E; Bosland, Maarten C

2007-02-01

Dehydroepiandrosterone (DHEA) is a potent inhibitor of prostate carcinogenesis in rats. However, concerns related to the possible androgenicity of DHEA may preclude its use for chemoprevention of human prostate cancer. Studies were performed to compare the androgenicity of DHEA and a fluorinated DHEA analog, 16alpha-fluoro-5-androsten-17-one (fluasterone), and to determine the chemopreventive activity of fluasterone in the rat prostate. Comparisons of accessory sex gland weight and histology in gonadectomized male rats demonstrated that fluasterone is less androgenic than is DHEA. Fluasterone conferred significant protection against prostate carcinogenesis induced in Wistar-Unilever rats by a sequential regimen of N-methyl-N-nitrosourea+testosterone. Chronic administration of fluasterone at levels of 2000 and 1000 mg/kg diet reduced the incidence of adenocarcinoma in the dorsolateral/anterior prostate from 64% in dietary controls to 28 and 31%, respectively. Other than a dose-related suppression of body weight gain, chronic exposure to fluasterone induced no clinical evidence of toxicity; suppression of body weight gain may be either a pharmacological effect or a minimally toxic effect of the compound. These data demonstrate that a minimally androgenic analog of DHEA protects against prostate carcinogenesis induced in rats by a chemical carcinogen + androgen. The reduced androgenicity of fluasterone may obviate toxicities associated with the androgenicity of the parent compound. On this basis, fluasterone merits consideration for evaluation in clinical trials for prostate cancer prevention. The chemopreventive activity of a non-androgenic DHEA analog suggests that at least a portion of the chemopreventive activity of DHEA in the rat prostate is unrelated to hormonal effects.

Assessment of serum dehydroepiandrosterone sulphate in subjects during the pre-pubertal, pubertal, and adult stages of skeletal maturation.

PubMed

Srinivasan, Bhadrinath; Premkumar, Sridhar

2012-08-01

The aim of this cross-sectional study was to evaluate serum levels of the hormone, dehydroepiandrosterone sulphate (DHEAS), during the pre-pubertal, pubertal, and adult stages of skeletal maturation based on the methods of Björk and Grave and Brown of assessing hand-wrist radiographs. The levels of the DHEAS of each individual were measured using quantitative enzyme-linked immunosorbent assay and correlated with the corresponding stages in their hand-wrist radiograph. This study was performed on 60 subjects (30 females and 30 males) aged from 7 to 30 years. Analysis of variance followed by a Tukey honestly significant difference test showed that the serum levels of the DHEAS were statistically significant at (P < 0.01) in all three groups. The serum levels were significant (P < 0.05) when each of the three groups were individually compared with the other two groups. The mean DHEAS levels were 0.43 ± 0.28, 2.17 ± 0.92, and 4.60 ± 1.34 μg/ml in the pre-pubertal, pubertal, and adult groups, respectively. There was a gradual increase in the hormonal level with progressing skeletal age. The adult group showed the highest DHEAS level and the pre-pubertal group the lowest. Serum levels of DHEAS showed a constant increase from pre-puberty to adulthood, and at the same level of skeletal maturation, both females and males had similar hormone levels. This finding highlights the fact that the hormone DHEAS plays a significant role and can be a valuable tool in assessing skeletal maturation.

Determination of dehydroepiandrosterone and its biologically active oxygenated metabolites in human plasma evinces a hormonal imbalance during HIV-TB coinfection.

PubMed

Vecchione, María Belén; Eiras, Javier; Suarez, Guadalupe Verónica; Angerami, Matías Tomás; Marquez, Cecilia; Sued, Omar; Ben, Graciela; Pérez, Héctor Miguel; Gonzalez, Diego; Maidana, Patricia; Mesch, Viviana; Quiroga, María Florencia; Bruttomesso, Andrea Claudia

2018-04-27

An estimated one third of the world's population is affected by latent tuberculosis (TB), which once active represents a leading cause of death among infectious diseases. Human immunodeficiency virus (HIV) infection is a main predisposing factor to TB reactivation. Individuals HIV-TB co-infected develop a chronic state of inflammation associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This results in a hormonal imbalance, disturbing the physiological levels of cortisol and dehydroepiandrosterone (DHEA). DHEA and its oxygenated metabolites androstenediol (AED), androstenetriol (AET) and 7-oxo-DHEA are immunomodulatory compounds that may regulate physiopathology in HIV-TB co-infection. In order to study possible changes in plasma levels of these hormones, we developed an approach based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To our knowledge, this represents the first report of their simultaneous measurement in HIV-TB individuals and the comparison with healthy donors, obtaining statistically higher plasma levels of DHEA, AET and 7-oxo-DHEA in patients. Moreover, we found that concentrations of 7-oxo-DHEA positively correlated with absolute CD4+ T cell counts, nadir CD4+ T cell values and with individuals who presented TB restricted to the lungs. This research contributes to understanding the role of these hormones in HIV-TB and emphasizes the importance of deepening their study in this context.

Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): II. Effects of urbanization, food supplementation and social stress.

PubMed

Wright, Sarah; Fokidis, H Bobby

2016-09-01

Perturbations in an organism's environment can induce significant shifts in hormone secretory patterns. In this context, the glucocorticoid (GC) steroids secreted by the adrenal cortex have received much attention from ecologists and behaviorists due to their role in the vertebrate stress response. Adrenal GCs, such as corticosterone (CORT), are highly responsive to instability in environmental and social conditions. However, little is understood about how adrenal dehydroepiandrosterone (DHEA) is influenced by changing conditions. We conducted field experiments to determine how circulating CORT and DHEA vary during restraint stress in the male northern cardinals (Cardinalis cardinalis). Specifically, we examined how four different changes in the physical (urbanization and food availability) and social (territorial conflict, distress of a mate) environment affect CORT and DHEA levels. The majority of cardinals responded to restraint stress by increasing and decreasing CORT and DHEA, respectively, however this depended on sampling context. Cardinals sampled from urban habitats had both lower initial and restraint stress CORT concentrations, but a comparable DHEA pattern to those sampled from a forest. Supplementing food to territorial males did not alter circulating initial DHEA or CORT concentrations nor did it change the response to restraint stress when compared to unsupplemented controls. Exposing cardinals to varying durations of song playback, which mimics a territorial intrusion, did not affect CORT levels, but did attenuate the DHEA response to restraint stress. Examining a larger dataset of males captured before, after or at the same time as their female mate, allowed us to address how the stress of a captured mate affected the male's CORT and DHEA response. Males showed elevated initial and restraint CORT and DHEA when their female mate was captured first. Taken together, these data demonstrate that both CORT and DHEA secretion patterns depends on

Hormonal causes of male sexual dysfunctions and their management (hyperprolactinemia, thyroid disorders, GH disorders, and DHEA).

PubMed

Maggi, Mario; Buvat, Jaques; Corona, Giovanni; Guay, André; Torres, Luiz Otavio

2013-03-01

Besides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD). To review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD. A systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence-Based Medicine-Levels of Evidence (March 2009) was applied when possible. The most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed. Only severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL-induced suppression on gonadotropin secretion. The latter is PRL-level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin-like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function. While the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in

Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7α-hydroxy dehydroepiandrosterone and 7α-hydroxy pregnenolone

PubMed Central

Rose, Ken A.; Stapleton, Genevieve; Dott, Karin; Kieny, Marie Paule; Best, Ruth; Schwarz, Margrit; Russell, David W.; Björkhem, Ingemar; Seckl, Jonathan; Lathe, Richard

1997-01-01

Steroids produced locally in brain (neurosteroids), including dehydroepiandrosterone (DHEA), influence cognition and behavior. We previously described a novel cytochrome P450, Cyp7b, strongly expressed in rat and mouse brain, particularly in hippocampus. Cyp7b is most similar to steroidogenic P450s and potentially could play a role in neurosteroid metabolism. To examine the catalytic activity of the enzyme mouse Cyp7b cDNA was introduced into a vaccinia virus vector. Extracts from cells infected with the recombinant showed NADPH-dependent conversion of DHEA (Km, 13.6 μM) and pregnenolone (Km, 4.0 μM) to slower migrating forms on thin layer chromatography. The expressed enzyme was less active against 25-hydroxycholesterol, 17β-estradiol and 5α-androstane-3β,17β-diol, with low to undetectable activity against progesterone, corticosterone, and testosterone. On gas chromatography and mass spectrometry of the Cyp7b metabolite of DHEA the retention time and fragmentation patterns were identical to those obtained with authentic 7α-hydroxy DHEA. The reaction product also comigrated on thin layer chromatography with 7α-hydroxy DHEA but not with 7β-hydroxy DHEA; when [7α-3H]pregnenolone was incubated with Cyp7b extracts the extent of release of radioactivity into the medium suggested that hydroxylation was preferentially at the 7α position. Brain extracts also efficiently liberated tritium from [7α-3H]pregnenolone and converted DHEA to a product with a chromatographic mobility indistinguishable from 7α-hydroxy DHEA. We conclude that Cyp7b is a 7α-hydroxylase participating in the synthesis, in brain, of neurosteroids 7α-hydroxy DHEA, and 7α-hydroxy pregnenolone. PMID:9144166

Hyperandrogenism due to a testosterone-secreting Sertoli-Leydig cell tumor associated with a dehydroepiandrosterone sulfate-secreting adrenal adenoma in a postmenopausal woman: case presentation and review of literature.

PubMed

Herrera, Jorge D; Davidson, Jaime A; Mestman, Jorge H

2009-03-01

To report a case of hyperandrogenism attributable to the presence of an adrenal adenoma secreting dehydroepiandrosterone sulfate (DHEA-S) and an ovarian Sertoli-Leydig cell tumor secreting testosterone in a postmenopausal woman. The laboratory, radiologic, and pathologic findings in our case are described. In addition, the pertinent literature is reviewed. A 56-year-old woman presented with a history of gradual increase in facial and body hair, scalp hair loss, male pattern baldness, and deepening of her voice, beginning a few years after spontaneous menopause at age 49 years. She had hypertension, obesity, and type 2 diabetes mellitus. Laboratory tests showed elevated levels of total testosterone (348 ng/dL) and DHEA-S (2,058 microg/dL), and a left adrenal tumor (3 by 4 cm) was detected on abdominal computed tomographic scan. Laparoscopic left adrenalectomy was performed, and the pathologic diagnosis was adrenal adenoma. The DHEA-S returned to normal levels, but the serum testosterone concentration remained elevated. Transvaginal ultrasonography disclosed an ovarian tumor. Bilateral oophorectomy was performed, and an ovarian Sertoli-Leydig cell tumor was diagnosed. The hormonal and clinical picture normalized after this surgical intervention. After extensive review of the literature, we believe that this is the first reported case of a coincidental DHEA-S-secreting adrenal adenoma and a testosterone- secreting ovarian Leydig cell tumor causing signs of virilization.

Serum dehydroepiandrosterone sulfate and incident depression in the elderly: the Pro.V.A. study.

PubMed

Veronese, Nicola; De Rui, Marina; Bolzetta, Francesco; Zambon, Sabina; Corti, Maria Chiara; Baggio, Giovannella; Toffanello, Elena Debora; Crepaldi, Gaetano; Perissinotto, Egle; Manzato, Enzo; Sergi, Giuseppe

2015-08-01

Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but contrasting findings are available. Therefore, we investigated whether high serum DHEAS levels were associated with any protective effect on incident depression and incident severe depression in a representative group of elderly men and women. In a population-based cohort longitudinal study in the general community, 789 older participants without depression and cognitive impairment at the baseline were included, among 3,099 screened subjects. Serum DHEAS levels were determined based on blood samples; incident depression and severe depression were diagnosed by means of the Geriatric Depression Scale (GDS) and confirmed by geriatricians skilled in psychogeriatric medicine. No baseline differences were found in GDS across age- and gender-specific tertiles of serum DHEAS. Over 4.4 years of follow-up, 137 new cases of depression were recorded. Of them, 35 among men and 64 in women were cases of incident severe depression. Cox's regression analysis, adjusted for potential confounders, revealed that higher DHEAS levels were associated with reduced risk of incident depression irrespective of gender (HR: 0.30; 95% CI: 0.09-0.96; Wald χ(2) = 4.09; df = 1; p = 0.04; women: HR: 0.31; 95% CI: 0.14-0.69; Wald χ(2) = 8.37; df = 1; p = 0.004) and of severe incident depression only in men (HR: 0.25; 95% CI: 0.06-0.99; Wald χ(2) = 4.05; df = 1; p = 0.04). Higher serum DHEAS levels were found to be significantly protective for the onset of depression irrespective of gender, whereas only in men was this association found also for incident severe depression. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Habitual sleep quality and diurnal rhythms of salivary cortisol and dehydroepiandrosterone in postmenopausal women.

PubMed

Huang, Tianyi; Poole, Elizabeth M; Vetter, Celine; Rexrode, Kathryn M; Kubzansky, Laura D; Schernhammer, Eva; Rohleder, Nicolas; Hu, Frank B; Redline, Susan; Tworoger, Shelley S

2017-10-01

Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a potential mechanism linking sleep and cardiometabolic disorders. However, the associations of two primary outputs of the HPA axis, cortisol and its antagonist dehydroepiandrosterone (DHEA), with sleep are less well studied. In the Nurses' Health Study II, 233 postmenopausal women provided five timed saliva samples over one day (immediately upon waking, 45min, 4h, and 10h after waking, and prior to going to sleep) to measure cortisol and DHEA. Of these, 209 completed assessment of their habitual sleep patterns using the Pittsburgh Sleep Quality Index (PSQI). We used piecewise linear mixed models to compare cross-sectional associations of slopes reflecting diurnal cortisol and DHEA rhythms with overall sleep quality and with seven sub-components. Overall, we observed no differences in the diurnal patterns of cortisol or DHEA between good versus poor sleepers as assessed by the global PSQI score. However, longer sleep latency was associated with significantly reduced cortisol awakening rise (p=0.02). Poorer subjective sleep quality (p=0.02), shorter sleep duration (p=0.02), and lower sleep efficiency (p=0.03) were associated with slower rate of cortisol decline later in the day. Women reporting daytime dysfunction had a sharper cortisol decline early in the day (p=0.03) but a flattened decline later in the day (p=0.01). The differences in diurnal patterns of DHEA between good versus poor sleepers, though less pronounced, were similar in direction to those of cortisol. Self-reported sleep duration, efficiency, latency and daytime dysfunction were associated with altered diurnal rhythms of cortisol and, to a lesser extent, DHEA. These findings provide support for the interplay between sleep and the HPA axis that may contribute to cardiometabolic disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dehydroepiandrosterone sulfate (DHEAS) suppresses P2X purinoceptor-coupled responses in PC12 cells.

PubMed

Liu, P S; Hsieh, H L; Lin, C M

2001-09-01

Some steroids rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels in addition to their well-known genomic effects via intracellular steroid receptors. Such effects were found in GABA receptor, nicotinic receptors, yet not investigated in P2X purinoceptors. In this study, the effects of dehydroepiandrosterone sulfate on the P2 purinoceptor was investigated. Results show that dehydroepiandrosterone sulfate acutely inhibits P2X purinoceptor functions in PC12 cells. Dehydroepiandrosterone sulfate suppressed ATP-induced cytosolic free calcium concentration ([Ca(2+)](i)) rise, cytosolic free sodium concentration ([Na(+)](i)) rise, and dopamine secretion in the presence of external calcium, but had no effect on ATP-induced [Ca(2+)](i) rise in the absence of external calcium or on UTP-induced [Ca(2+)](i) rise in the absence or presence of external calcium. Our data show that dehydroepiandrosterone sulfate exerted its effect on P2X, but not on the P2Y purinoceptors found in PC12 cells. Estradiol and estrone have similar effects on P2X purinoceptor, but dehydroepiandrosterone and progesterone do not.

Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress.

PubMed

Herrera-Pérez, J J; Martínez-Mota, L; Jiménez-Rubio, G; Ortiz-López, L; Cabrera-Muñoz, E A; Galindo-Sevilla, N; Zambrano, E; Hernández-Luis, F; Ramírez-Rodríguez, G B; Flores-Ramos, M

2017-03-15

Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging. Copyright © 2017 Elsevier B.V. All rights reserved.

Androgens and innate immunity in rehabilitated semi-captive orangutans (Pongo pygmaeus morio) from Malaysian Borneo.

PubMed

Prall, Sean P; Ambu, Laurentius; Nathan, Senthilvel; Alsisto, Sylvia; Ramirez, Diana; Muehlenbein, Michael P

2015-06-01

Despite the implications for the development of life-history traits, endocrine-immune trade-offs in apes are not well studied. This is due, in part, to difficulty in sampling wild primates, and lack of methods available for immune measures using samples collected noninvasively. Evidence for androgen-mediated immune trade-offs in orangutans is virtually absent, and very little is known regarding their pattern of adrenal development and production of adrenal androgens. To remedy both of these deficiencies, sera were collected from orangutans (Pongo pygmaeus morio) (N = 38) at the Sepilok Orangutan Rehabilitation Centre, Sabah, Malaysia, during routine health screenings. Testosterone, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-sulfate (DHEA-S) were assayed, along with two measures of functional innate immunity. DHEA-S concentrations, but not DHEA, increased with age in this sample of 1-18 year old animals. DHEA concentrations were higher in animals with higher levels of serum bacteria killing ability, while DHEA-S and testosterone concentrations were higher in animals with reduced complement protein activity. Patterns of DHEA-S concentration in this sample are consistent with patterns of adrenarche observed in other apes. Results from this study suggest that in addition to testosterone, DHEA and DHEA-S may have potent effects on immunological activity in this species. © 2015 Wiley Periodicals, Inc.

A genetic study of dehydroepiandrosterone sulfate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

PubMed

An, P; Rice, T; Gagnon, J; Hong, Y; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2000-03-01

Familial aggregation and possible major gene effects were evaluated for the baseline serum dehydroepiandrosterone sulfate (DHEAS) level and the change in DHEAS in response to a 20-week exercise training program in a sample of 481 individuals from 99 Caucasian families who were sedentary at baseline and who participated in the HERITAGE Family Study. Baseline DHEAS levels were not normally distributed, and were therefore logarithmically transformed and adjusted for the effects of age and sex prior to genetic analysis. The DHEAS response to training was computed as the simple difference, post-training minus baseline, and was adjusted for the baseline DHEAS level, age, and sex. Maximal (genetic and familial environmental) heritabilities (using a familial correlation model) reached 58% and 30% for the baseline and the response to training, respectively. Our estimate for the baseline is generally in agreement with previous reports, suggesting that the magnitude of the familial effect underlying this phenotype in these sedentary families is similar to that in the general population. However, segregation analysis showed no evidence for a multifactorial familial component in data for either the baseline or the response to training. Rather, a major additive gene controlling the baseline was found. For the response to training in the complete sample, transmission of the major effect from parents to offspring was ambiguous, but in a subset of 56 "responsive" families (with at least 1 family member whose response to training was greater than 1 standard deviation) this major effect was Mendelian in nature. The putative major genes accounted for 50% and 33% of the variance for the baseline and the response to training, respectively. The novel finding in this study is that the baseline DHEAS level and the change in DHEAS in response to training may be influenced by major gene effects.

Dehydroepiandrosterone Potentiates Native Ionotropic ATP Receptors Containing the P2X2 Subunit in Rat Sensory Neurones

PubMed Central

De Roo, Mathias; Rodeau, Jean-Luc; Schlichter, Rémy

2003-01-01

We have studied the modulatory effect of dehydroepiandrosterone (DHEA), the most abundant neurosteroid produced by glial cells and neurones, on membrane currents induced by the activation of ionotropic ATP (P2X) receptors in neonatal rat dorsal root ganglion neurones. ATP (1 μm) induced three types of currents/responses termed F (fast and transient), S (slowly desensitizing) and M (mixed, sum of F- and S-type responses). DHEA (10 nm to 100 μm) concentration-dependently increased the amplitude of plateau-like currents of S- and M-type responses evoked by submaximal (1 μm) but not saturating (100 μm or 1 mM) concentrations of ATP. αβ-Methylene ATP (αβme-ATP, 5 μm) also evoked F-, S- and M-type responses, the plateau phases of which were potentiated by lowering external pH (6.3) and by ivermectin (IVM, 3 μm), indicating the presence heteromeric P2X2-containing receptors and possibly of functional native P2X4/6 receptors. There was a strict correlation between the potentiating effects of low pH and DHEA on αβme-ATP responses but not between that of IVM and DHEA, suggesting that DHEA selectively modulated P2X2-containing receptors. DHEA also potentiated putative homomeric P2X2 receptor responses recorded in the continuous presence of 1 μm 2′-(or 3′)-O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate (TNP-ATP). Our results constitute the first demonstration of a fast potentiation of P2X receptors by a neurosteroid and suggest that DHEA could be an endogenous modulator of P2X2-containing receptors thereby contributing to the facilitation of the detection and/or the transmission of nociceptive messages, particularly under conditions of inflammatory pain where the P2X receptor signalling pathway appears to be upregulated. PMID:12844512

Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus Erythematosus: The Role of the Extrapituitary Prolactin Promoter Polymorphism at -1149G/T.

PubMed

Treadwell, Edward L; Wiley, Kenneth; Word, Beverly; Melchior, William; Tolleson, William H; Gopee, Neera; Hammons, George; Lyn-Cook, Beverly D

2015-01-01

Systemic lupus erythematosus (SLE) has shown an association with high levels of prolactin, low levels of dehydroepiandrosterone (DHEA), and induction of inflammatory cytokines in the serum of patients with the disease. This preliminary study examined the relevance of a -1149G/T functional single-nucleotide polymorphism (SNP) (rs1341239) in the promoter of the extrapituitary prolactin gene in a cohort of African American and European American women with lupus. Examination of this SNP revealed that the -1149TT genotype was correlated with higher levels of prolactin in serum and prolactin gene expression (p = 0.0001) in peripheral blood mononuclear cells (PBMCs). Lower levels of DHEA in serum were demonstrated in lupus patients (p = 0.001); those with the -1149TT genotype had the lowest levels of DHEA. Furthermore, a small subset of women who were on DHEA therapy and had a TT genotype showed a significant decrease in prolactin gene expression and lower disease activity scores (SLEDAI). Lupus patients, particularly African Americans, had significantly higher levels of IL-6 (p = 0.0001) and TNF-α (p = 0.042). This study suggests that the -1149TT genotype may be a risk factor for lupus and may predict who could possibly benefit from DHEA therapy; therefore, these results should be validated in a larger cohort with all ethnic groups.

Hair cortisol and dehydroepiandrosterone concentrations in naturally Taenia solium infected pigs in Tanzania.

PubMed

Trevisan, Chiara; Montillo, Marta; Prandi, Alberto; Mkupasi, Ernatus M; Ngowi, Helena A; Johansen, Maria V

2017-05-15

The aim of this study was to measure hair cortisol and dehydroepiandrosterone (DHEA) concentrations in naturally Taenia solium infected and non-infected control pigs and assess the effect of an environmental change on the aforementioned parameters. Three hair patches were obtained from 13 T. solium infected and 15 non-infected controls sows, respectively corresponding to 3 time points (prior to, at and approximately two weeks after arrival at the research facility). Cortisol and DHEA were extracted using methanol and analysed by radio immune assay. Mean hair cortisol concentrations were significantly lower (p<0.001) in T. solium infected (4.7±3.0pg/mg) compared to control pigs (9.0±3.7pg/mg) prior to arrival at the research facility, however no significant difference was observed between the two groups at arrival and after approximately two weeks. Similar patterns were also observed for DHEA concentrations (infected pigs 253.9±82.3pg/mg, control pigs 387.7±116.4pg/mg) (p<0.001). Results showed that lean animals had significantly higher cortisol concentrations in both groups, infected and controls pigs, while DHEA was not significantly different between lean and normal animals. Results of this study have shown that an environmental change could have an effect on pigs' hormonal levels suggesting an undergoing adaptation process. After the pigs were kept under the same conditions, fed and watered ad libitum, no significant differences were observed between the groups, but a drop in DHEA concentrations was observed in all the pigs. Weight however had an effect on cortisol levels as lean animals had significantly higher cortisol concentrations in both groups, compared to normal pigs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Oriental Medicine Kyung-Ok-Ko Prevents and Alleviates Dehydroepiandrosterone-Induced Polycystic Ovarian Syndrome in Rats

PubMed Central

Lee, Jin Moo; Bae, Chun-Sik; Kim, Sung-Hoon; Ryu, Jong Hoon; Cho, Ik-Hyun

2014-01-01

Kyung-Ok-Ko (KOK), a traditional herbal prescription composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in traditional Oriental medicine as a vitalizing medicine or as the prescription for patients with age-associated disorders such as amnesia and stroke. However, the potential protective value of KOK for the treatment of polycystic ovarian syndrome (PCOS) is largely unknown. We investigated whether pre-administration (daily from 2 hours before PCOS induction) and post-administration (daily after induction of PCOS) of KOK (0.5, 1.0, and 2.0 g/kg/day, p.o.) could have a protective effect in a dehydroepiandrosterone (DHEA, s.c.)-induced PCOS rat model. Pre-administration of KOK significantly decreased the elevated body weight and ovary weight, elevated size and number of follicular cysts, elevated level of serum glucose, and estradiol after DHEA injection. KOK reduced the elevated percentage of CD8 (+) T lymphocytes in lymph nodes, the elevated mRNA expression of CD11b and CD3 in ovaries, and infiltration of macrophages in ovarian tissue with PCOS. KOK diminished the increased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), chemokines (IL-8, MCP-1), and iNOS in the ovaries, and increased the reduced mRNA expression of growth factors (EGF, TGF-β) by DHEA injection. Post-administration of KOK also improved the DHEA-induced PCOS-like symptoms, generally similar to those evident from pre-administration of KOK. KOK may effectively prevent and improve DHEA-induced PCOS via anti-inflammatory action, indicating its preventive and therapeutic potential for suppressing PCOS. PMID:24520334

Oriental medicine Kyung-Ok-Ko prevents and alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats.

PubMed

Jang, Minhee; Lee, Min Jung; Lee, Jin Moo; Bae, Chun-Sik; Kim, Sung-Hoon; Ryu, Jong Hoon; Cho, Ik-Hyun

2014-01-01

Kyung-Ok-Ko (KOK), a traditional herbal prescription composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in traditional Oriental medicine as a vitalizing medicine or as the prescription for patients with age-associated disorders such as amnesia and stroke. However, the potential protective value of KOK for the treatment of polycystic ovarian syndrome (PCOS) is largely unknown. We investigated whether pre-administration (daily from 2 hours before PCOS induction) and post-administration (daily after induction of PCOS) of KOK (0.5, 1.0, and 2.0 g/kg/day, p.o.) could have a protective effect in a dehydroepiandrosterone (DHEA, s.c.)-induced PCOS rat model. Pre-administration of KOK significantly decreased the elevated body weight and ovary weight, elevated size and number of follicular cysts, elevated level of serum glucose, and estradiol after DHEA injection. KOK reduced the elevated percentage of CD8 (+) T lymphocytes in lymph nodes, the elevated mRNA expression of CD11b and CD3 in ovaries, and infiltration of macrophages in ovarian tissue with PCOS. KOK diminished the increased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), chemokines (IL-8, MCP-1), and iNOS in the ovaries, and increased the reduced mRNA expression of growth factors (EGF, TGF-β) by DHEA injection. Post-administration of KOK also improved the DHEA-induced PCOS-like symptoms, generally similar to those evident from pre-administration of KOK. KOK may effectively prevent and improve DHEA-induced PCOS via anti-inflammatory action, indicating its preventive and therapeutic potential for suppressing PCOS.

Metabolism of dehydroepiandrosterone sulfate and estrone-sulfate by human platelets.

PubMed

Garrido, A; Munoz, Y; Sierralta, W; Valladares, L

2012-01-01

The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H]-DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H]-17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol.

HIV-TB coinfection impairs CD8(+) T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses.

PubMed

Suarez, Guadalupe V; Angerami, Matías T; Vecchione, María B; Laufer, Natalia; Turk, Gabriela; Ruiz, Maria J; Mesch, Viviana; Fabre, Bibiana; Maidana, Patricia; Ameri, Diego; Cahn, Pedro; Sued, Omar; Salomón, Horacio; Bottasso, Oscar A; Quiroga, María F

2015-09-01

Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (TTE ) CD8(+) T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8(+) T cells, and their modulation by DHEA during HIV-TB coinfection. CD8(+) T cells from HIV-TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8(+) T cells. Notably, CD8(+) T cells from HIV-TB patients displayed higher Terminal Effector (TTE ) CD45RA(dim) proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8(+) T cells from HIV-TB patients increased although restricted to the CD27(+) population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8(+) T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8(+) T cells from HIV-TB patients. Our data suggest that HIV-TB coinfection promotes a deficient CD8(+) T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8(+) T-cell functions during HIV-TB coinfection. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of dehydroepiandrosterone administration on recovery from mix-type exercise training-induced muscle damage.

PubMed

Liao, Yi-Hung; Liao, Kun-Fu; Kao, Chung-Lan; Chen, Chung-Yu; Huang, Chih-Yang; Chang, Wei-Hsiang; Ivy, John L; Bernard, Jeffrey R; Lee, Shin-Da; Kuo, Chia-Hua

2013-01-01

This study aimed to determine the role of DHEA-S in coping against the exercise training mixing aerobic and resistance components. During 5-day successive exercise training, 16 young male participants (19.2 ± 1.2 years) received either a placebo (flour capsule) or DHEA (100 mg/day) in a double-blinded and placebo-controlled design. Oral DHEA supplementation significantly increased circulating DHEA-S by 2.5-fold, but a protracted drop (~35 %) was observed from Day 3 during training. In the Placebo group, only a minimal DHEA-S reduction (~17 %) was observed. Changes in testosterone followed a similar pattern as DHEA-S. Muscle soreness was elevated significantly on Day 2 for both groups to a similar extent. Lower muscle soreness was observed in the DHEA-supplemented group on Day 3 and Day 6. In the Placebo group, training increased circulating creatine kinase (CK) levels by approximately ninefold, while only a threefold increase was observed in the DHEA-supplemented group. This mix-type exercise training improved glucose tolerance in both groups, while lowering the insulin response to the glucose challenge, but no difference between treatments was observed. Our results suggest that DHEA-S may play a role in protecting skeletal muscle from exercise training-induced muscle damage.

The diurnal patterns of cortisol and dehydroepiandrosterone in relation to intense aerobic exercise in recreationally trained soccer players.

PubMed

Labsy, Z; Prieur, F; Le Panse, B; Do, M C; Gagey, O; Lasne, F; Collomp, K

2013-03-01

Diurnal patterns of cortisol and dehydroepiandrosterone (DHEA) secretion, the two main peripheral secretory products of the hypothalamic-pituitary-adrenal neuroendocrine stress axis, have been well characterized in rest conditions but not in relation to physical exercise. The purpose of this investigation was therefore to determine the effects of an intense 90-min aerobic exercise on the waking diurnal cortisol and DHEA cycles on three separate days [without exercise, with morning exercise (10:00-11:30 h), and with afternoon exercise (14:00-15:30 h)] in nine recreationally trained soccer players. Saliva samples were collected at awakening, 30 min after awakening, and then every 2 h from 08:00 to 22:00 h. A burst of secretory activity was found for cortisol (p < 0.01) but not for DHEA after awakening. Overall, diurnal decline for both adrenal steroids was observed on resting and exercise days under all conditions. However, there was a significant increase in salivary cortisol concentrations on the morning-exercise and afternoon-exercise days at, respectively, 12:00 h (p < 0.05) and 16:00 h (p < 0.01), versus the other trials. This acute response to exercise was not evident for DHEA. The results of this investigation indicate that 90 min of intense aerobic exercise does not affect the circadian pattern of salivary adrenal steroids in recreationally trained athletes over a 16-h waking period, despite a transitory increase in post-exercise cortisol concentration. Further studies are necessary to determine whether these results are applicable to elite athletes or patients with cortisol or DHEA deficiency.

Long-Term Administration of Dehydroepiandrosterone Accelerates Glucose Catabolism via Activation of PI3K/Akt-PFK-2 Signaling Pathway in Rats Fed a High-Fat Diet

PubMed Central

Kang, Jian; Ge, Chongyang; Yu, Lei; Li, Longlong; Ma, Haitian

2016-01-01

Dehydroepiandrosterone (DHEA) has a fat-reducing effect, while little information is available on whether DHEA regulates glucose metabolism, which would in turn affect fat deposition. To investigate the effects of DHEA on glucose metabolism, rats were administered a high-fat diet containing either 0 (HCG), 25 (HLG), 50 (HMG), or 100 (HHG) mg·kg-1 DHEA per day via gavage for 8 weeks. Results showed that long-term administration of DHEA inhibited body weight gain in rats on a high-fat diet. No statistical differences in serum glucose levels were observed, whereas hepatic glycogen content in HMG and HHG groups and muscle glycogen content in HLG and HMG groups were higher than those in HCG group. Glucokinase, malate dehydrogenase and phosphofructokinase-2 activities in HMG and HHG groups, pyruvate kinase and succinate dehydrogenase activities in HMG group, and pyruvate dehydrogenase activity in all DHEA treatment groups were increased compared with those in HCG group. Phosphoenolpyruvate carboxykinase and glycogen phosphorylase mRNA levels were decreased in HMG and HHG groups, whereas glycogen synthase-2 mRNA level was increased in HMG group compared with those in HCG. The abundance of Glut2 mRNA in HMG and HHG groups and Glut4 mRNA in HMG group was higher than that in HCG group. DHEA treatment increased serum leptin content in HMG and HHG groups compared with that in HCG group. Serum insulin content and insulin receptor mRNA level in HMG group and insulin receptor substrate-2 mRNA level in HMG and HHG group were increased compared with those in HCG group. Furthermore, Pi3k mRNA level in HMG and Akt mRNA level in HMG and HHG groups were significantly increased than those in HCG group. These data showed that DHEA treatment could enhance glycogen storage and accelerate glucose catabolism in rats fed a high-fat diet, and this effect may be associated with the activation of PI3K/Akt-PFK-2 signaling pathway. PMID:27410429

Long-Term Administration of Dehydroepiandrosterone Accelerates Glucose Catabolism via Activation of PI3K/Akt-PFK-2 Signaling Pathway in Rats Fed a High-Fat Diet.

PubMed

Kang, Jian; Ge, Chongyang; Yu, Lei; Li, Longlong; Ma, Haitian

2016-01-01

Dehydroepiandrosterone (DHEA) has a fat-reducing effect, while little information is available on whether DHEA regulates glucose metabolism, which would in turn affect fat deposition. To investigate the effects of DHEA on glucose metabolism, rats were administered a high-fat diet containing either 0 (HCG), 25 (HLG), 50 (HMG), or 100 (HHG) mg·kg-1 DHEA per day via gavage for 8 weeks. Results showed that long-term administration of DHEA inhibited body weight gain in rats on a high-fat diet. No statistical differences in serum glucose levels were observed, whereas hepatic glycogen content in HMG and HHG groups and muscle glycogen content in HLG and HMG groups were higher than those in HCG group. Glucokinase, malate dehydrogenase and phosphofructokinase-2 activities in HMG and HHG groups, pyruvate kinase and succinate dehydrogenase activities in HMG group, and pyruvate dehydrogenase activity in all DHEA treatment groups were increased compared with those in HCG group. Phosphoenolpyruvate carboxykinase and glycogen phosphorylase mRNA levels were decreased in HMG and HHG groups, whereas glycogen synthase-2 mRNA level was increased in HMG group compared with those in HCG. The abundance of Glut2 mRNA in HMG and HHG groups and Glut4 mRNA in HMG group was higher than that in HCG group. DHEA treatment increased serum leptin content in HMG and HHG groups compared with that in HCG group. Serum insulin content and insulin receptor mRNA level in HMG group and insulin receptor substrate-2 mRNA level in HMG and HHG group were increased compared with those in HCG group. Furthermore, Pi3k mRNA level in HMG and Akt mRNA level in HMG and HHG groups were significantly increased than those in HCG group. These data showed that DHEA treatment could enhance glycogen storage and accelerate glucose catabolism in rats fed a high-fat diet, and this effect may be associated with the activation of PI3K/Akt-PFK-2 signaling pathway.

Effects of prolonged stress on salivary cortisol and dehydroepiandrosterone: a study of a two-week teaching practice.

PubMed

Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Sugaya, Nagisa; Nomura, Shinobu

2012-06-01

This study investigated variations in salivary levels of cortisol and dehydroepiandrosterone (DHEA) in a prolonged stressful situation (a two-week teaching practice). Thirty-three women for whom a two-week teaching practice at a kindergarten was scheduled were asked to collect saliva samples at awakening, 30 min after awakening, and bedtime at four time points: two weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. In addition, they completed questionnaires for assessing perceived stress and subjective moods on each day. A linear mixed model indicated that cortisol levels significantly increased during the first and second week of the practice compared with those before and after the practice period, and that DHEA levels significantly decreased after the practice period compared with those at the other time points. Further, cortisol awakening response after the practice period significantly reduced compared with that at the other time points. Scores of perceived stress and negative moods were also higher during the practice period. This study showed that prolonged stress affected cortisol and DHEA secretion during as well as after the stress period. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors.

PubMed

Pediaditakis, Iosif; Iliopoulos, Ioannis; Theologidis, Ioannis; Delivanoglou, Nickoleta; Margioris, Andrew N; Charalampopoulos, Ioannis; Gravanis, Achille

2015-01-01

Dehydroepiandosterone (DHEA), the most abundant steroid in humans, affects multiple cellular functions of the endocrine, immune, and nervous systems. However, up to quite recently, no receptor has been described specifically for it, whereas most of its physiological actions have been attributed to its conversion to either androgens or estrogens. DHEA interacts and modulate a variety of membrane and intracellular neurotransmitter and steroid receptors. We have recently reported that DHEA protects neuronal cells against apoptosis, interacting with TrkA, the high-affinity prosurvival receptor of the neurotrophin, nerve growth factor. Intrigued by its pleiotropic effects in the nervous system of a variety of species, we have investigated the ability of DHEA to interact with the other two mammalian neurotrophin receptors, ie, the TrkB and TrkC, as well as their invertebrate counterparts (orthologs) in mollusks Lymnaea and Aplysia and in cephalochordate fish Amphioxus. Amazingly, DHEA binds to all Trk receptors, although with lower affinity by 2 orders of magnitude compared with that of the polypeptidic neurotrophins. DHEA effectively induced the first step of the TrkA and TrkC receptors activation (phosphorylation at tyrosine residues), including the vertebrate neurotrophin nonresponding invertebrate Lymnaea and Aplysia receptors. Based on our data, we hypothesize that early in evolution, DHEA may have acted as a nonspecific neurotrophic factor promoting neuronal survival. The interaction of DHEA with all types of neurotrophin receptors offers new insights into the largely unidentified mechanisms of its actions on multiple tissues and organs known to express neurotrophin receptors.

Plasma testosterone and dehydroepiandrosterone sulfate in male and female patients with dysthymic disorder.

PubMed

Markianos, Manolis; Tripodianakis, John; Sarantidis, Democritos; Hatzimanolis, John

2007-08-01

Depressive symptomatology has been connected with an activation of the hypothalamus-pituitary-adrenal axis and, in several studies, with reduced androgen levels, while administration of androgens, usually in older subjects, may have positive effects on mood, both in males and females. Regarding dysthymic disorder (DD), low serum testosterone levels have been reported in older males, while information on younger male or on female patients is lacking. We assessed the serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS) and cortisol in male and female patients with DD, and compared them to the levels of sex and age matched controls. Eighteen male and 43 female patients in the age range of 22 to 71 years were studied and diagnosed according to the Scheduled Diagnostic Interview for DSM-IV axis I disorders (SCID). Depressive symptomatology was assessed using the Hamilton Depression Rating Scale. Subgroups with subjects below or over 50 years of age were also built and compared. Serum T levels were lower than controls mainly in the subjects aged below 50 years, in both genders. More pronounced were reductions in DHEAS levels both in male and female patients, while cortisol levels were normal or reduced. T levels were positively correlated to both DHEAS and cortisol. The negative correlations of DHEAS and T to age were significant for all groups and subgroups, except in the group of male patients. Four male patients (22%) had T levels below 2.0 ng/ml. Male and female patients with DD aged below 50 years show reduced gonadal and adrenal androgen levels, and normal to low cortisol levels. These neuroendocrine characteristics differentiate DD from depression, and place this diagnostic group closer to posttraumatic stress disorder.

Gender differences in susceptibility to schizophrenia: Potential implication of neurosteroids.

PubMed

Huang, Yu-Chi; Hung, Chi-Fa; Lin, Pao-Yen; Lee, Yu; Wu, Chih-Ching; Hsu, Su-Ting; Chen, Chien-Chih; Chong, Mian-Yoon; Lin, Chieh-Hsin; Wang, Liang-Jen

2017-10-01

Past research has indicated gender differences in the clinical characteristics and course of schizophrenia. In this study, we investigated whether gender differences in the manifestation of schizophrenia are correlated with neurosteroids, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and pregnenolone. We further explored the potential relationship between the aforementioned neurosteroids and psychopathology. We recruited 65 schizophrenic patients (36 males and 29 females) and 103 healthy control subjects (47 males and 56 females) and obtained blood samples from the subjects in the morning while in a fasting state to determine the serum levels of DHEA, DHEA-S, and pregnenolone. The psychopathology and mood symptoms of patients with schizophrenia were evaluated using the Positive and Negative Syndrome Scale (PANSS) and 17-item Hamilton Depression Rating Scale, respectively. Compared to the male control subjects, male patients with schizophrenia had significantly lower serum levels of DHEA and pregnenolone. In males with schizophrenia, the serum levels of DHEA and DHEA-S were associated with the age of onset and the duration of illness, while pregnenolone levels were associated with general symptoms of the PANSS. However, none of the neurosteroid levels were different between the female patients with schizophrenia and the female controls, and no significant correlation between neurosteroid levels and psychopathology evaluations was found among the schizophrenic females. Neurosteroids, including DHEA, DHEA-S, and pregnenolone, are involved in the pathophysiology of schizophrenia in male patients, but not in female ones. Therefore, our findings suggest that neurosteroids may be associated with gender differences in susceptibility to schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.

PubMed

Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar

2012-01-01

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.

Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons

PubMed Central

Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar

2012-01-01

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS. PMID:22431997

Deficiency of Gpr1 improves steroid hormone abnormality in hyperandrogenized mice.

PubMed

Yang, Ya-Li; Sun, Li-Feng; Yu, Yan; Xiao, Tian-Xia; Wang, Bao-Bei; Ren, Pei-Gen; Tang, Hui-Ru; Zhang, Jian V

2018-05-24

Polycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes. Many researches use dehydroepiandrosterone (DHEA) to induce PCOS in pubertal mouse models. The aim of this study was to investigate the role of GPR1 in dehydroepiandrosterone (DHEA)-induced hyperandrogenized mice. Prepubertal C57BL/6 mice (25 days of age) and Gpr1-deficient mice were each divided into two groups and injected daily with sesame oil with or without DHEA (6 mg/100 g) for 21 consecutive days. Hematoxylin and eosin (H&E) staining was performed to determine the characteristics of the DHEA-treated ovaries. Real-time PCR was used to examine steroid synthesis enzymes gene expression. Granulosa cell was cultured to explore the mechanism of DHEA-induced, GPR1-mediated estradiol secretion. DHEA treatment induced some aspects of PCOS in wild-type mice, such as increased body weight, elevated serum testosterone, increased number of small, cystic, atretic follicles, and absence of corpus luteum in ovaries. However, Gpr1 deficiency significantly attenuated the DHEA-induced weight gain and ovarian phenotype, improving steroidogenesis in ovaries and estradiol synthesis in cultured granulosa cells, partially through mTOR signaling. In conclusion, Gpr1 deficiency leads to the improvement of steroid synthesis in mice hyperandrogenized with DHEA, indicating that GPR1 may be a therapeutic target for DHEA-induced hyperandrogenism.

Diurnal patterns of salivary cortisol and DHEA using a novel collection device: Electronic monitoring confirms accurate recording of collection time using this device

PubMed Central

Laudenslager, Mark L.; Calderone, Jacqueline; Philips, Sam; Natvig, Crystal; Carlson, Nichole E.

2013-01-01

The accurate indication of saliva collection time is important for defining the diurnal decline in salivary cortisol as well as characterizing the cortisol awakening response.. We tested a convenient and novel collection device for collecting saliva on strips of filter paper in a specially constructed booklet for determination of both cortisol and DHEA. In the present study, 31 healthy adults (mean age 43.5 yrs.) collected saliva samples four times a day on three consecutive days using filter paper collection devices (Saliva Procurement and Integrated Testing (SPIT) booklet) which were maintained during the collection period in a large plastic bottle with an electronic monitoring cap. Subjects were asked to collect saliva samples at awakening, 30 min. after awakening, before lunch and 600 min. after awakening. The time of awakening and the time of collection before lunch were allowed to vary by each subjects’ schedule. A reliable relationship was observed between the time recorded by the subject directly on the booklet and the time recorded by electronic collection device (n = 286 observations; r2 = 0.98). However, subjects did not consistently collect the saliva samples at the two specific times requested, 30 and 600 min. after awakening. Both cortisol and DHEA revealed diurnal declines.. In spite of variance in collection times at 30 min. and 600 min. after awakening, the slope of the diurnal decline in both salivary cortisol and DHEA were similar when we compared collection tolerances of ± 7.5 and ± 15 min. for each steroid.. These unique collection booklets proved to be a reliable method for recording collection times by subjects as well as for estimating diurnal salivary cortisol and DHEA patterns. PMID:23490073

Diurnal patterns of salivary cortisol and DHEA using a novel collection device: electronic monitoring confirms accurate recording of collection time using this device.

PubMed

Laudenslager, Mark L; Calderone, Jacqueline; Philips, Sam; Natvig, Crystal; Carlson, Nichole E

2013-09-01

The accurate indication of saliva collection time is important for defining the diurnal decline in salivary cortisol as well as characterizing the cortisol awakening response. We tested a convenient and novel collection device for collecting saliva on strips of filter paper in a specially constructed booklet for determination of both cortisol and DHEA. In the present study, 31 healthy adults (mean age 43.5 years) collected saliva samples four times a day on three consecutive days using filter paper collection devices (Saliva Procurement and Integrated Testing (SPIT) booklet) which were maintained during the collection period in a large plastic bottle with an electronic monitoring cap. Subjects were asked to collect saliva samples at awakening, 30 min after awakening, before lunch and 600 min after awakening. The time of awakening and the time of collection before lunch were allowed to vary by each subjects' schedule. A reliable relationship was observed between the time recorded by the subject directly on the booklet and the time recorded by electronic collection device (n=286 observations; r(2)=0.98). However, subjects did not consistently collect the saliva samples at the two specific times requested, 30 and 600 min after awakening. Both cortisol and DHEA revealed diurnal declines. In spite of variance in collection times at 30 min and 600 min after awakening, the slope of the diurnal decline in both salivary cortisol and DHEA was similar when we compared collection tolerances of ±7.5 and ±15 min for each steroid. These unique collection booklets proved to be a reliable method for recording collection times by subjects as well as for estimating diurnal salivary cortisol and DHEA patterns. Copyright © 2013 Elsevier Ltd. All rights reserved.

Essential Oil of Japanese Cedar (Cryptomeria japonica) Wood Increases Salivary Dehydroepiandrosterone Sulfate Levels after Monotonous Work.

PubMed

Matsubara, Eri; Tsunetsugu, Yuko; Ohira, Tatsuro; Sugiyama, Masaki

2017-01-21

Employee problems arising from mental illnesses have steadily increased and become a serious social problem in recent years. Wood is a widely available plant material, and knowledge of the psychophysiological effects of inhalation of woody volatile compounds has grown considerably. In this study, we established an experimental method to evaluate the effects of Japanese cedar wood essential oil on subjects performing monotonous work. Two experiment conditions, one with and another without diffusion of the essential oil were prepared. Salivary stress markers were determined during and after a calculation task followed by distribution of questionnaires to achieve subjective odor assessment. We found that inhalation of air containing the volatile compounds of Japanese cedar wood essential oil increased the secretion of dehydroepiandrosterone sulfate (DHEA-s). Slight differences in the subjective assessment of the odor of the experiment rooms were observed. The results of the present study indicate that the volatile compounds of Japanese cedar wood essential oil affect the endocrine regulatory mechanism to facilitate stress responses. Thus, we suggest that this essential oil can improve employees' mental health.

Association of working hours with biological indices related to the cardiovascular system among engineers in a machinery manufacturing company.

PubMed

Sasaki, T; Iwasaki, K; Oka, T; Hisanaga, N

1999-10-01

A field survey of 278 engineers (20-59 years) in a machinery manufacturing company was conducted to investigate the association of working hours with biological indices related to the cardiovascular system (heart rate variability, blood pressure and serum levels of magnesium, dehydroepiandrosterone sulfate <DHEA-S> and cholesterol). Average working hours (defined as <"hours at workplace" + "half a commuting time">) and sleeping hours in this study were 60.2 +/- 6.3 hr/week and 6.6 +/- 0.8 hr/day respectively. There were no significant relationships between working hours and biological indices related to the cardiovascular system, but sleeping hours was closely related to working hours negatively. Furthermore, the serum DHEA-S level was significantly related to sleeping hours positively. Combining these two results, it appeared that long working hours might lower the serum DHEA-S level due to the reduction of sleeping hours.

Adrenal maturation, nutritional status, and mucosal immunity in Bolivian youth.

PubMed

Hodges-Simeon, Carolyn R; Prall, Sean P; Blackwell, Aaron D; Gurven, Michael; Gaulin, Steven J C

2017-09-10

Humans-and several other apes-exhibit a unique pattern of post-natal adrenal maturation; however, the causes and consequences of variation in adrenal development are not well understood. In this study, we examine developmental and age-related maturation of the adrenal gland (measured via dehydroepiandrosterone-sulfate [DHEA-S]) for potential life-history associations with growth and mucosal immunity in a rural population of immune-challenged Bolivian juveniles and adolescents. Salivary DHEA-S, anthropometrics, and salivary mucosal immunity (secretory IgA [sIgA]) were measured in 171 males and females, aged 8-23. Males with greater energy (i.e. fat) stores showed higher DHEA-S levels. Controlling for age and energetic condition (to control for phenotypic correlation), higher DHEA-S was associated with higher mucosal immunity (sIgA) among both males and females. Higher DHEA-S levels were positively associated with growth (i.e. height and strength) in males. In accordance with predictions derived from life-history theory, males with higher energy stores secrete more adrenal androgens. This suggests that adrenal maturation is costly and subject to constraints; that is, only males with sufficient reserves will invest in accelerated adrenal maturation. Further, DHEA-S appears to have a measureable influence on immunocompetence in adolescent males and females; therefore, deficits in DHEA-S may have important consequences for health and maturation during this period. Adrenal maturation is an important, but understudied component of human growth and development. © 2017 Wiley Periodicals, Inc.

The effect of gonadal and adrenal steroid therapy on skeletal health in adolescents and young women with anorexia nervosa

PubMed Central

DiVasta, Amy D.; Feldman, Henry A.; Giancaterino, Courtney; Rosen, Clifford J.; LeBoff, Meryl S.; Gordon, Catherine M.

2012-01-01

Anorexia nervosa (AN) is characterized by subnormal estrogen and dehydroepiandrosterone (DHEA) levels. We sought to determine whether the combination of DHEA + estrogen/progestin is superior to placebo in preserving skeletal health over 18 months in AN. Females with AN, aged 13 to 27 years, were recruited for participation in this double-blind, placebo-controlled, randomized trial. Ninety-four subjects were randomized, of whom 80 completed baseline assessments and received either study drug (oral micronized DHEA 50 mg + 20 µg ethinyl estradiol/0.1 mg levonorgestrel combined oral contraceptive pill [COC] daily; n = 43) or placebo (n = 37). Serial measurements of areal bone mineral density (aBMD), bone turnover markers, and serum hormone concentrations were obtained. Sixty subjects completed the 18-month trial. Spinal and whole-body aBMD z scores were preserved in the DHEA + COC group, but decreased in the placebo group (comparing trends, P = .008 and P = .001, respectively). Bone turnover markers initially declined in subjects receiving DHEA + COC and then returned to baseline. No differences in body composition, adverse effects of therapy, or alterations in biochemical safety parameters were observed. Combined therapy with DHEA + COC appears to be safe and effective for preventing bone loss in young women with AN, whereas placebo led to decreases in aBMD. Dehydroepiandrosterone + COC may be safely used to preserve bone mass as efforts to reverse the nutritional, psychological, and other hormonal components of AN are implemented. PMID:22257645

Effects of Dehydroepiandrosterone Supplementation during Stressful Military Training: A Randomized, Controlled, Double-Blind Field Study

DTIC Science & Technology

2011-01-01

DHEAS. All samples were assayed for salivary DHEA in duplicate using a highly sensitive enzyme immunoassay (Salimetrics, LLC). The test used 50ml of...p , 0.0001, n ¼ 39). Similarly, samples were assayed for salivary DHEAS in duplicate using a highly sensitive enzyme immuno- assay (Salimetrics, LLC...assayed for salivary testosterone. This was performed in duplicate using a highly sensitive enzyme immunoassay (Salimetrics, LLC). The test used 25ml of

Neurosteroid dehydroepiandrosterone sulphate inhibits persistent sodium currents in rat medial prefrontal cortex via activation of sigma-1 receptors.

PubMed

Cheng, Zheng-Xiang; Lan, Dan-Mei; Wu, Pei-Ying; Zhu, Yan-Hua; Dong, Yi; Ma, Lan; Zheng, Ping

2008-03-01

Dehydroepiandrosterone sulphate is one of the most important neurosteroids. In the present paper, we studied the effect of dehydroepiandrosterone sulphate on persistent sodium currents and its mechanism and functional consequence with whole-cell patch clamp recording method combined with a pharmacological approach in the rat medial prefrontal cortex slices. The results showed that dehydroepiandrosterone sulphate inhibited the amplitude of persistent sodium currents and the inhibitory effect was significant at 0.1 microM, reached maximum at 1 microM and decreased with the increase in the concentrations of above 1 microM. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was canceled by the Gi protein inhibitor and the protein kinase C inhibitor, but not by the protein kinase A inhibitor. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was also canceled by the sigma-1 receptor blockers and the sigma-1 receptor agonist could mimic the effect of dehydroepiandrosterone sulphate. Dehydroepiandrosterone sulphate had no significant influence on neuronal excitability but could significantly inhibit chemical inhibition of mitochondria-evoked increase in persistent sodium currents. These results suggest that dehydroepiandrosterone sulphate inhibits persistent sodium currents via the activation of sigma-1 receptors-Gi protein-protein kinase C-coupled signaling pathway, and the main functional consequence of this effect of DHEAS is presumably to protect neurons under ischemia.

Adrenal androgen excess and body mass index in polycystic ovary syndrome.

PubMed

Moran, Carlos; Arriaga, Monica; Arechavaleta-Velasco, Fabian; Moran, Segundo

2015-01-07

Context: Adrenal hyperandrogenism affects around 25% of polycystic ovary syndrome (PCOS) patients but its relation to obesity is not totally understood. Objective: To assess dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) levels in relation to body mass index (BMI) in PCOS. Design: Prospective observational study. Setting: Institutional practice at an Obstetrics/Gynecology hospital. Patients or Other Participants: This study included 136 PCOS patients, 20-35 years old, and 42 matched-age control women. The participants were classified with the BMI cutoff value of 27 kg/m 2 as follows: 1) high-BMI PCOS patients; 2) low-BMI PCOS patients; 3) high-BMI control women; and 4) low-BMI control women. The data were reanalyzed with the BMI cutoff value of 30 kg/m 2 to corroborate the findings in obese and non-obese patients. Intervention(s): Blood samples were taken. Main Outcome Measure(s): LH, FSH, insulin, T, androstenedione (A 4 ), DHEA, DHEAS, and glucose levels were determined. Homeostatic model assessment was calculated. Pelvic and abdominal ultrasound for ovarian morphology and adipose tissue, respectively, were performed. Results: Obese PCOS patients presented significantly more insulin resistance than non-obese PCOS patients. The LH levels and LH/FSH ratio were significantly higher in low-BMI than in high-BMI PCOS patients. The A 4 and DHEAS levels were significantly higher in non-obese than in obese PCOS patients. A significant correlation between LH and A 4 in non-obese PCOS patients was observed. The frequency of hyperandrogenism by increased A 4 , and DHEA along with DHEAS was significantly higher in low-BMI PCOS patients compared to high-BMI PCOS patients. Some findings observed with the BMI cutoff value of 27 kg/m 2 changed with the cutoff value of 30 kg/m 2 . Conclusions: Low BMI more than high BMI is associated with increased LH, high A 4 , DHEA and DHEAS levels in PCOS patients. The BMI cutoff value of 27 kg/m 2 classified better

Adrenal androgen excess and body mass index in polycystic ovary syndrome.

PubMed

Moran, Carlos; Arriaga, Monica; Arechavaleta-Velasco, Fabian; Moran, Segundo

2015-03-01

Adrenal hyperandrogenism affects approximately 25% of polycystic ovary syndrome (PCOS) patients but its relation to obesity is not totally understood. This study aimed to assess dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) levels in relation to body mass index (BMI) in PCOS. This was a prospective observational study at an institutional practice at an obstetrics/gynecology hospital. The study included 136 PCOS patients, 20-35 years old, and 42 age-matched control women. The participants were classified with the BMI cutoff value of 27 kg/m(2) as follows: 1) high-BMI PCOS patients; 2) low-BMI PCOS patients; 3) high-BMI control women; and 4) low-BMI control women. The data were reanalyzed with the BMI cutoff value of 30 kg/m(2) to corroborate the findings in obese and nonobese patients. Blood samples were taken and LH, FSH, insulin, T, androstenedione (A4), DHEA, DHEAS, and glucose levels were determined. Homeostatic model assessment was calculated. Pelvic and abdominal ultrasound for ovarian morphology and adipose tissue, respectively, were performed. Obese PCOS patients presented significantly more insulin resistance than nonobese PCOS patients. The LH levels and LH/FSH ratio were significantly higher in low-BMI than in high-BMI PCOS patients. The A4 and DHEAS levels were significantly higher in nonobese than in obese PCOS patients. A significant correlation between LH and A4 in nonobese PCOS patients was observed. The frequency of hyperandrogenism by increased A4, and DHEA along with DHEAS was significantly higher in low-BMI PCOS patients compared with high-BMI PCOS patients. Some findings observed with the BMI cutoff value of 27 kg/m(2) changed with the cutoff value of 30 kg/m(2). Low BMI more so than high BMI is associated with increased LH, high A4, DHEA, and DHEAS levels in PCOS patients. The BMI cutoff value of 27 kg/m(2) classified better than 30 kg/m(2) for hormonal and metabolic characteristics.

Polymorphisms in AKR1C4 and HSD3B2 and differences in serum DHEAS and progesterone are associated with paranoid ideation during mania or hypomania in bipolar disorder.

PubMed

Johansson, Anette G M; Nikamo, Pernilla; Schalling, Martin; Landén, Mikael

2012-09-01

Paranoia is commonly a mood-incongruent psychotic symptom of mania which may be related to dopamine dysregulation. Progesterone and its metabolite allopregnanolone (ALLO) have been found in animals to antagonize the effects of dopamine. We therefore examined serum progesterone, its endogenous antagonist DHEAS and polymorphisms of the genes coding for certain steroidogenetic enzymes (AKR1C4, HSD3B2, and SRD5A1) in 64 males and 96 females with bipolar 1 or 2 disorder with or without paranoid ideation during mood elevation. Euthymic morning serum progesterone, DHEAS and cortisol concentrations were measured in males and in premenopausal women who were in follicular phase and not taking oral contraceptives. In women only, SNPs in AKR1C4 reduced the likelihood of having exhibited paranoid ideation by circa 60%. The haplotype of all 4 SNPs in the AKR1C4 gene reduced the risk of exhibiting paranoia by 80% (OR 0.19, 95% CI 0.06-0.61, p=0.05). A history of paranoid ideation was not, however, related to progesterone or DHEAS concentration. Serum DHEAS and progesterone concentrations were lower in men who had shown paranoid ideation during mania/hypomania compared with those who had not (F=7.30, p=0.006) however this was not coupled to polymorphisms in the selected genes. The ancestral G in rs4659174 in HSD3B2 was in men associated with a lower risk of paranoid ideation (likelihood ratio χ(2) 3.97, p=0.046, OR 0.31 (95% CI 0.10-0.96)) but did not correlate with hormone concentrations. Hence, gene variants in the steroidogenetic pathway and steroids concentration differences may be involved in the susceptibility to paranoia during mood elevation. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

Predictors of lapse in first week of smoking abstinence in PTSD and non-PTSD smokers.

PubMed

Beckham, Jean C; Calhoun, Patrick S; Dennis, Michelle F; Wilson, Sarah M; Dedert, Eric A

2013-06-01

Retrospective research suggests smokers with posttraumatic stress disorder (PTSD) lapse more quickly after their quit date. Ecological momentary assessment (EMA) research is needed to confirm the presence of early smoking lapse in PTSD and form conceptualizations that inform intervention. Smokers with (n = 55) and without (n = 52) PTSD completed alarm-prompted EMA of situational and psychiatric variables the week before and after a quit date, and self-initiated EMA following smoking lapses. Blood samples at baseline and on the quit date allowed assessment of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA(S)). PTSD was related to shorter time to lapse (hazard ratio [HR] = 1.677, 95% CI: 1.106-2.544). Increased smoking abstinence self-efficacy was related to longer time to lapse (HR = 0.608, 95% CI: 0.430-0.860). Analyses of participants' real-time reports revealed that smokers with PTSD were more likely to attribute first-time lapses to negative affect ( = 5.412, p = .020), and trauma reminders (Fisher's exact p = .003**). Finally, the quit date decrease in DHEA(S) was related to shorter time to lapse (HR = 1.009, 95% CI: 1.000-1.018, p < .05). Results provide evidence of shorter time to first smoking lapse in PTSD, and add to evidence that early lapse occasions are more strongly related to trauma reminders, negative affect, and cravings in smokers with PTSD.

The Effect of Steroid Hormones on the Physical Performance of Boys and Girls During an Olympic Weightlifting Competition.

PubMed

Crewther, Blair; Obminski, Zbigniew; Cook, Christian

2016-11-01

To examine the steroid hormone effect on the physical performance of young athletes during an Olympic weightlifting competition. 26 boys and 26 girls were monitored across 2 weightlifting competitions. Pre- and post-competition testosterone (T), cortisol (C) and dehydroepiandrosterone-sulfate (DHEA-s) were measured in blood, with pre-event free T (FT) and the free androgen index (FAI) calculated. Body mass (BM) and weightlifting performance were recorded. The boys had a larger BM, superior performance with more T, FT and a higher FAI than girls (p < .01). Although C (32%) and DHEA-s (8%) levels were elevated across competition, no sex differences in hormone reactivity were seen. In boys, DHEA-s correlated with performance (r = .46), but not after controlling for BM (r = .14). For girls, T correlated with performance (r = -0.51) after BM was controlled. The sex differences that emerge during puberty were observable, whereby the boys were larger and stronger with a more anabolic profile than girls. Individual DHEA-s (boys) and T (girls) levels were related to performance, but BM appeared to be acting as a mediating (boys) or suppressing (girls) variable. This adds new insight regarding the hormonal contribution to competitive performance in young athletes.

Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS).

PubMed

Kumar, Ashim; Woods, Keslie S; Bartolucci, Alfred A; Azziz, Ricardo

2005-06-01

To determine the prevalence of adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) using age- and race-specific normative values. Cross-sectional observational study. One hundred and eight-two (88 Black and 94 White) age-matched healthy eumenorrhoeic nonhirsute women (controls) and 213 (27 Black and 186 White) women with PCOS were recruited. Total testosterone (T), free T, androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS) and SHBG, as well as fasting insulin and glucose, were measured in plasma. The mean total T, free T, A4, DHEAS and body mass index (BMI) were higher in women with PCOS than in control women. DHEAS levels were significantly lower in Black controls than White controls, whereas fasting insulin and BMI were higher in Black controls. In control and Black PCOS women, DHEAS levels did not correlate with BMI, waist-to-hip ratio (WHR) or fasting insulin. Among White women with PCOS, DHEAS levels correlated negatively with BMI and fasting insulin. DHEAS levels decreased similarly with age in control and PCOS women of either race. For each race and age group the upper 95% normative values for log DHEAS was calculated, and the number of PCOS subjects with log DHEAS values above this level were assessed. The prevalence of supranormal DHEAS levels was 33.3% and 19.9%, respectively, among Black and White women with PCOS. The prevalence of DHEAS excess is approximately 20% among White and 30% among Black PCOS patients, when using age- and race-adjusted normative values. This study also indicates that the age-associated decline in DHEAS levels is observable and similar in both control and PCOS women, regardless of race. While BMI and fasting insulin had little impact on circulating DHEAS levels in healthy women, among White PCOS patients these parameters were negatively associated with circulating DHEAS levels.

High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome.

PubMed

Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong

2014-11-01

Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS. © 2014 by the Society for the Study of Reproduction, Inc.

Cell-targetable DNA nanocapsules for spatiotemporal release of caged bioactive small molecules

NASA Astrophysics Data System (ADS)

Veetil, Aneesh T.; Chakraborty, Kasturi; Xiao, Kangni; Minter, Myles R.; Sisodia, Sangram S.; Krishnan, Yamuna

2017-12-01

Achieving triggered release of small molecules with spatial and temporal precision at designated cells within an organism remains a challenge. By combining a cell-targetable, icosahedral DNA-nanocapsule loaded with photoresponsive polymers, we show cytosolic delivery of small molecules with the spatial resolution of single endosomes in specific cells in Caenorhabditis elegans. Our technology can report on the extent of small molecules released after photoactivation as well as pinpoint the location at which uncaging of the molecules occurred. We apply this technology to release dehydroepiandrosterone (DHEA), a neurosteroid that promotes neurogenesis and neuron survival, and determined the timescale of neuronal activation by DHEA, using light-induced release of DHEA from targeted DNA nanocapsules. Importantly, sequestration inside the DNA capsule prevents photocaged DHEA from activating neurons prematurely. Our methodology can in principle be generalized to diverse neurostimulatory molecules.

Inverse association of highly chlorinated dioxin congeners in maternal breast milk with dehydroepiandrosterone levels in three-year-old Vietnamese children.

PubMed

Kido, Teruhiko; Honma, Seijiro; Nhu, Dang Duc; Manh, Ho Dung; Van Tung, Dao; Liang, Sun Xian; Anh, Le Thai; Okamoto, Rie; Maruzeni, Shoko; Nakagawa, Hideaki; Hung, Nguyen Ngoc; Son, Le Ke

2016-04-15

This study aims to evaluate the endocrine-disrupting effect of dioxin congeners on adrenal steroid hormones in mother-child pairs. In our previous study, we found that cortisol and cortisone levels were higher in the blood and the saliva of mothers living in a dioxin hotspot area than in mothers from a non-exposed region in Vietnam. In this follow-up study, we determined the salivary steroid hormone levels in 49 and 55 three-year-old children of these mothers in the hotspot and non-exposed region, respectively. Steroid hormones were determined by liquid chromatography-tandem mass spectrometry, and dioxin in the maternal breast milk was determined by gas chromatography-mass spectrometry. Dioxin levels in the breast milk of mothers from the hotspot (median total toxic equivalents polychlorinated dibenzodioxins/polychlorinated dibenzofurans; (TEQ PCDD/Fs) of 11pg/g lipid) were three to four times higher than those of mothers in the non-exposed region (median TEQ PCDD/Fs of 3.07pg/g lipid). Salivary dehydroepiandrosterone (DHEA) levels in children were found to be significantly lower in the hotspot than in the non-exposed region, while cortisol and cortisone levels were not different between the two regions. Highly chlorinated dioxin congeners, such as octacholorodibenzodioxin (OCDD), 1,2,3,4,6,7,8-heptacholorodibenzodioxin (HpCDD) and 1,2,3,4 (or 6), 7,8-hexachlorodibenzodioxin Hx(CDD), showed stronger inverse associations with the children's salivary DHEA than other lowly chlorinated dioxin congeners. Glucocorticoid levels in the mothers exhibited a significantly positive correlation with OCDD and HpCDD/F (polychlorinated dibenzofurans). In conclusion, highly chlorinated dioxin congeners are more strongly correlated with endocrine-disrupting effects on adrenal hormones, resulting in high cortisol levels in the mothers and low DHEA levels in their three-year-old children. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuroprotective-Neurotrophic Effect of Endogenous Dehydroepiandrosterone Sulfate During Intense Stress Exposure

DTIC Science & Technology

2014-06-02

22 May 2014 Available online 2 June 2014 Keywords: DHEA sulfate Neurotrophin Nerve growth factor Testosterone Cortisol Stressa b s t r a c t Recent... neurotrophin salivary nerve growth factor (sNGF). In terms of total hormone output, the effect of DHEAS on sNGF was mediated by testosterone. Unlike...established criteria for causation. Published by Elsevier Inc.1. Introduction Neurotrophins are proteins found within a broad range of cell types in the

Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR).

PubMed

Gleicher, Norbert; Kim, Ann; Weghofer, Andrea; Shohat-Tal, Aya; Lazzaroni, Emanuela; Lee, Ho-Joon; Barad, David H

2013-01-01

To investigate whether androgen conversion rates after supplementation with dehydroepiandrosterone (DHEA) differ, and whether differences between patients with diminished ovarian reserve (DOR) are predictive of pregnancy chances in association with in vitro fertilization (IVF). In a prospective cohort study we investigated 213 women with DOR, stratified for age (≤ 38 or >38 years) and ovarian FMR1 genotypes/sub-genotypes. All women were for at least 6 weeks supplemented with 75 mg of DHEA daily prior to IVF, between initial presentation and start of 1st IVF cycles. Levels of DHEA, DHEA-sulfate (DHEAS), total T (TT) and free T (FT) at baseline ((BL)) and IVF cycle start ((CS)) were then compared between conception and non-conception cycles. Mean age for the study population was 41.5 ± 4.4 years. Forty-seven IVF cycles (22.1 %) resulted in clinical pregnancy. Benefits of DHEA on pregnancy rates were statistically associated with efficiency of androgen conversion from DHEA to T and amplitude of T gain. Younger women converted significantly more efficiently than older females, and selected FMR1 genotypes/sub-genotypes converted better than others. FSH/androgen and AMH/androgen ratios represent promising new predictors of IVF pregnancy chances in women with DOR. DOR at all ages appears to represent an androgen-deficient state, benefitting from androgen supplementation. Efficacy of androgen supplementation with DHEA, however, varies depending on female age and FMR1 genotype/sub-genotype. Further clarification of FMR1 effects should lead to better individualization of androgen supplementation, whether via DHEA or other androgenic compounds.

Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats.

PubMed

Naert, Gaëlle; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

2007-01-01

Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and have some antidepressant effects. BDNF is highly involved in regulation of the HPA axis, whereas neurosteroids effects have never been clearly established. In this systematic in vivo study, we showed that the principal neuroactive steroids, namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA axis activity, while also modulating central BDNF contents. In detail, DHEA, DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred concomitantly with BDNF modifications at the hippocampus, amygdala and hypothalamus levels. We showed that these neurosteroids induced rapid effects, probably via neurotransmitter receptors and delayed effects perhaps after metabolization in other neuroactive steroids. We highlighted that they had peripheral effects directly at the adrenal level by inducing CORT release, certainly after estrogenic metabolization. In addition, we showed that, at the dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In conclusion, these results highly suggest that part of the HPA axis and antidepressant effects of neuroactive steroids could be mediated by BDNF, particularly at the amygdala level. They also suggest that neurosteroids effects on central BDNF could partially explain the trophic properties of these molecules.

Salivary testosterone may not serve as a screening test in the diagnosis of biochemical hyperandrogenism.

PubMed

Ambroziak, Urszula; Kuryłowicz, Alina; Kępczyńska-Nyk, Anna; Kondracka, Agnieszka; Gajda, Sylvia; Sieńko, Damian

2018-06-01

The diagnosis of biochemical hyperandrogenism is still challenging because a set of appropriate, recommended diagnostic tests has not been established. In our study, we aimed to answer the question of whether salivary testosterone is a reliable test to establish the diagnosis of biochemical hyperandrogenism as compared to serum total testosterone (TT) measured either by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay and to assess which set of biochemical tests would be the most appropriate for the identification of biochemical hyperandrogenism. A total of 39 women, aged 18-45 years, with clinical or biochemical hyperandrogenism and 41 healthy individuals, aged 19-45 years, were enrolled in the study. Salivary testosterone was measured using the Salimetrics test. Serum TT was measured either using the LC-MS/MS method or immunoassay, and dehydroepiandrosterone sulphate (DHEA-S) and androstenedione were measured using LC-MS/MS. In 15 of 17 (88%) patients with elevated serum TT measured by LC-MS/MS and in 14 of 16 (87%) measured with immunoassay, salivary testosterone showed normal levels. In 11 of 39 women (28%) with normal serum testosterone levels, DHEA-S was elevated. All patients with elevated androstenedione presented with an elevated concentration of either serum testosterone or DHEA-S. Salivary testosterone measurement may lead to the underdiagnosis of biochemical hyperandrogenism. Both serum testosterone and DHEA-S should be measured in the endocrine work-up toward biochemical hyperandrogenism. © 2018 Japan Society of Obstetrics and Gynecology.

The "yin and yang" of the adrenal and gonadal systems in elite military men.

PubMed

Taylor, Marcus K; Hernández, Lisa M; Kviatkovsky, Shiloah A; Schoenherr, Matthew R; Stone, Michael S; Sargent, Paul

2017-05-01

We recently established daily, free-living profiles of the adrenal hormone cortisol, the (primarily adrenal) anabolic precursor dehydroepiandrosterone (DHEA) and the (primarily gonadal) anabolic hormone testosterone in elite military men. A prevailing view is that adrenal and gonadal systems reciprocally modulate each other; however, recent paradigm shifts prompted the characterization of these systems as parallel, cooperative processes (i.e. the "positive coupling" hypothesis). In this study, we tested the positive coupling hypothesis in 57 elite military men by evaluating associations between adrenal and gonadal biomarkers across the day. Salivary DHEA was moderately and positively coupled with salivary cortisol, as was salivary testosterone. Anabolic processes (i.e. salivary DHEA and testosterone) were also positively and reliably coupled across the day. In multivariate models, salivary DHEA and cortisol combined to account for substantial variance in salivary testosterone concentrations across the day, but this was driven almost exclusively by DHEA. This may reflect choreographed adrenal release of DHEA with testicular and/or adrenal release of testosterone, systemic conversion of DHEA to testosterone, or both. DHEA and testosterone modestly and less robustly predicted cortisol concentrations; this was confined to the morning, and testosterone was the primary predictor. Altogether, top-down co-activation of adrenal and gonadal hormone secretion may complement bottom-up counter-regulatory functions to foster anabolic balance and neuronal survival; hence, the "yin and yang" of adrenal and gonadal systems. This may be an adaptive process that is amplified by stress, competition, and/or dominance hierarchy.

Effect of prolonged stress on the adrenal hormones of individuals with irritable bowel syndrome.

PubMed

Sugaya, Nagisa; Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Nomura, Shinobu; Shimada, Hironori

2015-01-01

The purpose of this study was to investigate the effect of prolonged stress on the salivary adrenal hormones (cortisol, dehydroepiandrosterone [DHEA], DHEA-sulfate [DHEA-S]) of individuals with irritable bowel syndrome (IBS). The participants were female college students, including 10 with IBS and 16 without IBS (control group), who were scheduled for a 2-week teaching practice at a kindergarten. Participants were asked to collect saliva for determining adrenal hormones immediately and 30 min after awakening and before sleep, 2 weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. Regarding cortisol/DHEA ratio, significantly increased levels were found during the first week of the practice, and a significant interaction between group and time was found; the ratio at 30 min after awakening in the IBS group was higher than that in the control group. For the other adrenal hormone indexes, no significant differences due to the presence of IBS were found. Individuals with IBS showed an elevated cortisol/DHEA ratio after awakening compared with individuals without IBS, and the elevated ratio peaked under the prolonged stress. The present study suggests that the cortisol effect is dominant in individuals with IBS under prolonged stress.

TGFβ1 alters androgenic metabolites and hydroxysteroid dehydrogenase enzyme expression in human prostate reactive stromal primary cells: Is steroid metabolism altered by prostate reactive stromal microenvironment?

PubMed Central

Piao, Yun-shang; Wiesenfeld, Paddy; Sprando, Robert; Arnold, Julia T.

2013-01-01

The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory microenvironment may contribute to epithelial cancer progression. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant endogenous steroid hormone present in human serum and can be metabolized to DHEA, androgens and/or estrogens in peripheral tissues. We have previously reported that TGFβ1-induced reactive prostate stromal cells increase DHEA metabolism to active androgens and alter prostate cancer cell gene expression. While much of the focus on mechanisms of prostate cancer and steroid metabolism is in the epithelial cancer cells, this study focuses on TGFβ1-induced effects on DHEA metabolic pathways and enzymes in human prostate stromal cells. In DHEA-treated primary prostate stromal cells, TGFβ1 produced time- and dose-dependent increases in metabolism of DHEA to androstenedione and testosterone. Also TGFβ1-treated prostate stromal cells exhibited changes in the gene expression of enzymes involved in steroid metabolism including up-regulation of 3β hydroxysteroid dehydrogenase (HSD), and down-regulation of 17βHSD5, and 17βHSD2. These studies suggest that reactive prostate stroma and the inflammatory microenvironment may contribute to altered steroid metabolism and increased intratumoral androgens. PMID:23770322

TGFβ1 alters androgenic metabolites and hydroxysteroid dehydrogenase enzyme expression in human prostate reactive stromal primary cells: Is steroid metabolism altered by prostate reactive stromal microenvironment?

PubMed

Piao, Yun-shang; Wiesenfeld, Paddy; Sprando, Robert; Arnold, Julia T

2013-11-01

The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory microenvironment may contribute to epithelial cancer progression. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant endogenous steroid hormone present in human serum and can be metabolized to DHEA, androgens and/or estrogens in peripheral tissues. We have previously reported that TGFβ1-induced reactive prostate stromal cells increase DHEA metabolism to active androgens and alter prostate cancer cell gene expression. While much of the focus on mechanisms of prostate cancer and steroid metabolism is in the epithelial cancer cells, this study focuses on TGFβ1-induced effects on DHEA metabolic pathways and enzymes in human prostate stromal cells. In DHEA-treated primary prostate stromal cells, TGFβ1 produced time- and dose-dependent increases in metabolism of DHEA to androstenedione and testosterone. Also TGFβ1-treated prostate stromal cells exhibited changes in the gene expression of enzymes involved in steroid metabolism including up-regulation of 3β hydroxysteroid dehydrogenase (HSD), and down-regulation of 17βHSD5, and 17βHSD2. These studies suggest that reactive prostate stroma and the inflammatory microenvironment may contribute to altered steroid metabolism and increased intratumoral androgens. Published by Elsevier Ltd.

Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens.

PubMed

Paixão, L; Velez, L M; Santos, B R; Tusset, C; Lecke, S B; Motta, A B; Spritzer, P M

2016-08-01

Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.

Does ovulation affect performance in tennis players?

PubMed

Otaka, Machiko; Chen, Shu-Man; Zhu, Yong; Tsai, Yung-Shen; Tseng, Ching-Yu; Fogt, Donovan L; Lim, Boon-Hooi; Huang, Chih-Yang; Kuo, Chia-Hua

2018-01-01

Scientific data on the performance of collegiate female tennis players during the menstrual phases are scarce. Double-blind, counter-balanced, crossover trials were conducted to examine whether tennis performance was affected during menstruation, with and without dehydroepiandrosterone sulfate (DHEA-S) supplementation. Ten Division 1 collegiate tennis players (aged 18-22 years) were evenly assigned into placebo-supplemented and DHEA-supplemented (25 mg/day) trials. Treatments were exchanged among the participants after a 28-day washout. Tennis serve performance was assessed on the first day of menstrual bleeding (day 0/28) and on days 7, 14 and 21. Mood state was unaltered during the menstrual cycles in both trials. The lowest tennis serve performance score (speed times accuracy) occurred on day 14 (P=0.06 vs day 0; P=0.01 vs day 21) in both placebo and DHEA trials. Decreased performance on day 14 was explained by decreased accuracy (P=0.03 vs day 0/28; P=0.01 vs day 21), but not velocity itself. Isometric hip strength, but not quadriceps strength, was moderately lower on day 14 (P=0.08). Increasing plasma DHEA-S (by ~65%) during the DHEA-supplemented trial had no effects on mood state, sleep quality or tennis serve performance. We have shown that menses does not affect serve performance of collegiate tennis players. However, the observed decrement in the accuracy of serve speed near ovulation warrants further investigation.

Modulation of the phenotype and function of Mycobacterium tuberculosis-stimulated dendritic cells by adrenal steroids.

PubMed

Angerami, Matias; Suarez, Guadalupe; Pascutti, Maria Fernanda; Salomon, Horacio; Bottasso, Oscar; Quiroga, Maria Florencia

2013-07-01

Cell-mediated immunity, cytokines induced during the specific immune response and T-cell populations are crucial factors for containing Mycobacterium tuberculosis infection. Recent reports suggest a cross-regulation between adrenal steroids (glucocorticoids and dehydroepiandrosterone, DHEA) and the function of antigen-presenting cells (APCs). Therefore, we investigated the role of adrenal hormones on the functional capacity of M. tuberculosis-induced dendritic cells (DCs). Cortisol significantly inhibited the functions of M. tuberculosis-induced DCs. Interestingly, the presence of DHEA enhanced the M. tuberculosis-induced expression of MHC I, MHC II and CD86 and also increased ERK1/2 phosphorylation. Moreover, DHEA improved the production of IL-12 in response to M. tuberculosis stimulation, diminished IL-10 secretion and could not modify TNF-α synthesis. Importantly, we observed that DHEA enhanced the antigen-specific T-cell proliferation and IFN-γ production induced by M. tuberculosis-stimulated DC. These data show for the first time the relevance of the adrenal axis (especially of DHEA) in the modulation of DC function in the context of tuberculosis, a disease where the induction of a Th1 environment by APCs is crucial for the development of an effective immune response to the mycobacteria.

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.

Brief communication: Adrenal androgens and aging: Female chimpanzees (Pan troglodytes) compared with women.

PubMed

Blevins, James K; Coxworth, James E; Herndon, James G; Hawkes, Kristen

2013-08-01

Ovarian cycling continues to similar ages in women and chimpanzees yet our nearest living cousins become decrepit during their fertile years and rarely outlive them. Given the importance of estrogen in maintaining physiological systems aside from fertility, similar ovarian aging in humans and chimpanzees combined with somatic aging differences indicates an important role for nonovarian estrogen. Consistent with this framework, researchers have nominated the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), which can be peripherally converted to estrogen, as a biomarker of aging in humans and other primates. Faster decline in production of this steroid with age in chimpanzees could help explain somatic aging differences. Here, we report circulating levels of DHEAS in captive female chimpanzees and compare them with published levels in women. Instead of faster, the decline is slower in chimpanzees, but from a much lower peak. Levels reported for other great apes are lower still. These results point away from slowed decline but toward increased DHEAS production as one of the mechanisms underlying the evolution of human longevity. Copyright © 2013 Wiley Periodicals, Inc.

Effect of alcohol consumption on hormones involved in carbohydrate and lipid metabolism in premenopausal women

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

Law, J.S.; Bhathena, S.J.; Kim, Y.C.

Alcohol consumption alters carbohydrate and lipid metabolism which are in part regulated by pancreatic and adrenal hormones. The menstrual cycle per se produces changes in several peptide and steroid hormones besides the sex hormones. The authors investigated the effect of moderate alcohol consumption on plasma hormone levels in 40 premenopausal women. The subjects were fed controlled diets containing 35% of calories from fat. In a random crossover design women were given either alcohol or a soft-drink of equal caloric value for 3 menstrual cycles. Fasting blood samples were collected in the third cycle during follicular, ovulatory and luteal phases. Plasmamore » dehydroepiandrosterone-sulphate (DHEA-S), insulin, glucagon and cortisol levels were measured by radioimmunoassay. Moderate alcohol consumption had no effect on plasma insulin and DHEA-S levels but significantly increased glucagon and cortisol levels. Menstrual cycle per se affected plasma glucagon level in that the levels were higher during follicular phase than luteal phase. Thus, changes in carbohydrate and lipid metabolism following alcohol consumption are mediated in part by alterations in hormones involved in their metabolism.« less

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease.

PubMed

Hong, A Ram; Kim, Jung Hee; Hong, Eun Shil; Kim, I Kyeong; Park, Kyeong Seon; Ahn, Chang Ho; Kim, Sang Wan; Shin, Chan Soo; Kim, Seong Yeon

2015-09-01

Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively. Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

Parallel diurnal fluctuation of testosterone, androstenedione, dehydroepiandrosterone and 17OHprogesterone as assessed in serum and saliva: validation of a novel liquid chromatography-tandem mass spectrometry method for salivary steroid profiling.

PubMed

Mezzullo, Marco; Fazzini, Alessia; Gambineri, Alessandra; Di Dalmazi, Guido; Mazza, Roberta; Pelusi, Carla; Vicennati, Valentina; Pasquali, Renato; Pagotto, Uberto; Fanelli, Flaminia

2017-08-28

Salivary androgen testing represents a valuable source of biological information. However, the proper measurement of such low levels is challenging for direct immunoassays, lacking adequate accuracy. In the last few years, many conflicting findings reporting low correlation with the serum counterparts have hampered the clinical application of salivary androgen testing. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) makes it possible to overcome previous analytical limits, providing new insights in endocrinology practice. Salivary testosterone (T), androstenedione (A), dehydroepiandrosterone (DHEA) and 17OHprogesterone (17OHP) were extracted from 500µL of saliva, separated in 9.5 min LC-gradient and detected by positive electrospray ionization - multiple reaction monitoring. The diurnal variation of salivary and serum androgens was described by a four paired collection protocol (8 am, 12 am, 4 pm and 8 pm) in 19 healthy subjects. The assay allowed the quantitation of T, A, DHEA and 17OHP down to 3.40, 6.81, 271.0 and 23.7 pmol/L, respectively, with accuracy between 83.0 and 106.1% for all analytes. A parallel diurnal rhythm in saliva and serum was observed for all androgens, with values decreasing from the morning to the evening time points. Salivary androgen levels revealed a high linear correlation with serum counterparts in both sexes (T: R>0.85; A: R>0.90; DHEA: R>0.73 and 17OHP: R>0.89; p<0.0001 for all). Our LC-MS/MS method allowed a sensitive evaluation of androgen salivary levels and represents an optimal technique to explore the relevance of a comprehensive androgen profile as measured in saliva for the study of androgen secretion modulation and activity in physiologic and pathologic states.

Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects.

PubMed

Seibert, Julia; Hysek, Cédric M; Penno, Carlos A; Schmid, Yasmin; Kratschmar, Denise V; Liechti, Matthias E; Odermatt, Alex

2014-01-01

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-hour plasma steroid profiles. 16 healthy subjects (8 men, 8 women) were treated with single doses of MDMA (125 mg), methylphenidate (60 mg), MDMA + methylphenidate, and placebo on 4 separate days using a cross-over study design. Cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycorticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were repeatedly measured up to 24 h using liquid chromatography-tandem mass spectroscopy. MDMA significantly increased the plasma concentrations of cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone and also tended to moderately increase aldosterone levels compared with placebo. MDMA also increased the sum of cortisol + cortisone and the cortisol/cortisone ratio, consistent with an increase in glucocorticoid production. MDMA did not alter the levels of cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate did not affect any of the steroid concentrations, and it did not change the effects of MDMA on circulating steroids. In summary, the serotonin releaser MDMA has acute effects on circulating steroids. These effects are not observed after stimulation of the dopamine and norepinephrine systems with methylphenidate. The present findings support the view that serotonin rather than dopamine and norepinephrine mediates the acute pharmacologically induced stimulation of the hypothalamic-pituitary-adrenal axis in the absence of other stressors. © 2014 S. Karger AG, Basel.

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.

Fetal programming of adrenal androgen excess: lessons from a nonhuman primate model of polycystic ovary syndrome.

PubMed

Abbott, David H; Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Conley, Alan J

2008-01-01

Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of dehydroepiandrosterone sulfate (DHEAS), typical of polycystic ovary syndrome (PCOS) women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS.

Expression and activity of Rac1 is negatively affected in the dehydroepiandrosterone induced polycystic ovary of mouse

PubMed Central

2014-01-01

Background Polycystic ovarian syndrome (PCOS) is characterized by the presence of multiple follicular cysts, giving rise to infertility due to anovulation. This syndrome affects about 10% of women, worldwide. The exact molecular mechanism leading to PCOS remains obscure. RhoGTPase has been associated with oogenesis, but its role in PCOS remains unexplored. Therefore, we attempted to elucidate the Vav-Rac1 signaling in PCOS mice model. Methods We generated a PCOS mice model by injecting dehydroepiandrosterone (DHEA) for a period of 20 days. The expression levels of Rac1, pRac1, Vav, pVav and Caveolin1 were analyzed by employing immuno-blotting and densitometry. The association between Vav and Rac1 proteins were studied by immuno-precipitation. Furthermore, we analyzed the activity of Rac1 and levels of inhibin B and 17β-estradiol in ovary using biochemical assays. Results The presence of multiple follicular cysts in ovary were confirmed by histology. The activity of Rac1 (GTP bound state) was significantly reduced in the PCOS ovary. Similarly, the expression levels of Rac1 and its phosphorylated form (pRac1) were decreased in PCOS in comparison to the sham ovary. The expression level and activity (phosphorylated form) of guanine nucleotide exchanger of Rac1, Vav, was moderately down-regulated. We observed comparatively increased expressions of Caveolin1, 17β-estradiol, and inhibin B in the polycystic ovary. Conclusion We conclude that hyperandrogenization (PCOS) by DHEA diminishes ovarian Rac1 and Vav expression and activity along with an increase in expression of Caveolin1. This is accompanied by an increase in the intra-ovarian level of '17 β-estradiol and inhibin B. PMID:24628852

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

PubMed

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

2015-02-01

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

Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia.

PubMed

Dessein, P H; Shipton, E A; Joffe, B I; Hadebe, D P; Stanwix, A E; Van der Merwe, B A

1999-11-01

Neuroendocrine deficiencies have been implicated in fibromyalgia (FM). In the present study, adrenal androgen metabolites and their relationship with health status in FM were investigated. For comparison, serum levels of other implicated neuroendocrine mediators were correlated with health status. Fifty-seven consecutive women with FM completed the Fibromyalgia Impact Questionnaire (FIQ). Fasting blood samples were taken for measurement of dehydroepiandrosterone sulphate (DHEAS), free testosterone (T), cortisol, serotonin and insulin-like growth factor-1. Normal value for DHEAS and T were obtained from 114 controls. DHEAS levels were decreased significantly in pre- and postmenopausal patients (P<0.0001 and P<0.0005, respectively). T levels were decreased significantly in premenopausal and insignificantly in postmenopausal patients (P<0.0001 and P=0.06, respectively). The following correlations between neurohormonal levels and FIQ scores were found: DHEAS (after adjustment for age) vs. pain (P<0.001) and T (after adjustment for age) versus physical functioning (P=0.002). None of the other neurohormonal levels correlated significantly with any of the FIQ scores. IGF-1 levels were lower in the obese patients as compared to those who were non-obese (P=0.03). The BMI correlated positively with pain (P<0. 001) and inversely with DHEAS levels (P=0.006). After further adjustment for BMI, the correlation between age adjusted DHEAS and pain was no longer significant. Hyposecretion of adrenal androgens was documented in FM. This was more pronounced in obese patients. Low serum androgen levels correlated with poor health status in FM. Longitudinal studies are needed to elucidate whether these are cause and/or effect relationships.

Isaria fumosorosea KCh J2 Entomopathogenic Strain as an Effective Biocatalyst for Steroid Compound Transformations.

PubMed

Kozłowska, Ewa; Dymarska, Monika; Kostrzewa-Susłow, Edyta; Janeczko, Tomasz

2017-09-09

The catalytic activity of enzymes produced by an entomopathogenic filamentous fungus ( Isaria fumosorosea KCh J2) towards selected steroid compounds (androstenedione, adrenosterone, progesterone, 17α-methyltestosterone and dehydroepiandrosterone) was investigated. All tested substrates were efficiently transformed. The structure of the substrate has a crucial impact on regio- and stereoselectivity of hydroxylation since it affects binding to the active site of the enzyme. Androstenedione was hydroxylated in the 7α-position to give a key intermediate in the synthesis of the diuretic-7α-hydroxyandrost-4-ene-3,17-dione with 82% conversion. Adrenosterone and 17α-methyltestosterone were hydroxylated in the 6β-position. Hydroxylated derivatives such as 15β-hydroxy-17α-methyltestosterone and 6β,12β-dihydroxy-17α-methyltestosterone were also observed. In the culture of Isaria fumosorosea KCh J2, DHEA was effectively hydroxylated in the C-7 position and then oxidized to give 7-oxo-DHEA, 3β,7α- and 3β,7β-dihydroxy-17a-oxa-d-homo-androst-5-ene-17-one. We obtained 7β-OH-DHEA lactone with 82% yield during 3 days transformation of highly concentrated (5 g/L) DHEA.

Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosus: relation to other adrenal hormones.

PubMed

Vogl, Daniela; Falk, Werner; Dorner, Monika; Schölmerich, Jürgen; Straub, Rainer H

2003-02-01

In patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), low levels of adrenal steroids have been repeatedly demonstrated, but the site of alteration has not been exactly described because measurements of serum pregnenolone and 17-hydroxypregnenolone (17OHPreg) together with other adrenal steroids have never been performed. We measured serum levels of adrenal hormones such as pregnenolone, 17OHPreg, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), progesterone (P), 17-hydroxyprogesterone (17OHP), androstenedione (ASD), and cortisol in 24 healthy controls, 24 patients with RA, and 24 patients with SLE. Serum levels of pregnenolone were similar in RA and SLE patients as compared to healthy controls irrespective of prior prednisolone therapy. In all RA and SLE patients (including those with prior prednisolone treatment), serum levels of all measured hormones except pregnenolone were significantly lower as compared to controls. In RA patients without prior prednisolone treatment, serum levels of 17OHPreg, DHEA, cortisol, and ASD were similar to controls, and serum levels of P, 17OHP, and DHEAS were significantly lower as compared to controls. In SLE patients without prior prednisolone treatment, serum levels of 17OHPreg and cortisol were similar, and serum levels of P, 17OHP, ASD, DHEA, and DHEAS were significantly lower as compared to controls. The primary hormone of the adrenal steroid cascade, pregnenolone, is almost normal in RA and SLE irrespective of corticosteroid treatment. In patients with RA, we believe that there is a near normal P450scc reaction and a normal double step P450c17 reaction. In SLE patients, the P450scc reaction also seems normal but the second step of the P450c17 reaction seems to be inhibited. In both diseases, cortisol levels remain relatively stable at the expense of other adrenal hormones. This study revealed distinct changes of steroid pathways that are related to the disease entities.

Hyperandrogenism induces a proinflammatory TNFα response to glucose ingestion in a receptor-dependent fashion.

PubMed

González, Frank; Sia, Chang Ling; Bearson, Dawn M; Blair, Hilary E

2014-05-01

Hyperandrogenism and inflammation are related in polycystic ovary syndrome (PCOS). Hyperandrogenemia can induce inflammation in reproductive-age women, but the mechanism for this phenomenon is unclear. We examined the in vivo and in vitro effects of hyperandrogenism on mononuclear cell (MNC)-derived androgen receptor (AR) status and TNFα release. This study combined a randomized, controlled, double-blind protocol with laboratory-based cell culture experiments. This work was performed in an academic medical center. Lean, healthy, reproductive-age women were treated with 130 mg of dehydroepiandrosterone (DHEA) or placebo (n = 8 subjects each) for 5 days and also provided untreated fasting blood samples (n = 12 subjects) for cell culture experiments. AR mRNA content and TNFα release were measured before and after DHEA administration in the fasting state and 2 hours after glucose ingestion. TNFα release in the fasting state was also measured in cultured MNCs exposed to androgens with or without flutamide preincubation. At baseline, subjects receiving DHEA or placebo exhibited no significant difference in androgens and TNFα release from MNCs before and after glucose ingestion. Compared with placebo, DHEA administration raised levels of T, androstenedione, and DHEA sulfate, and increased MNC-derived AR mRNA content and TNFα release in the fasting state and in response to glucose ingestion. Compared with MNC exposure to baseline concentrations of DHEA (175 ng/dL) or T (50 ng/dL), the absolute change in TNFα release increased after exposure to T concentrations of 125 and 250 ng/dL and a DHEA concentration of 1750 ng/dL. Preincubation with flutamide reduced the TNFα response by ≥ 60% across all T concentrations. Androgen excess in vivo and in vitro comparable to what is present in PCOS increases TNFα release from MNCs of lean healthy reproductive-age women in a receptor-dependent fashion. Hyperandrogenemia activates and sensitizes MNCs to glucose in this

Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the Chianti Area (InCHIANTI) study.

PubMed

Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo; Bandinelli, Stefania; Ling, Shari M; Metter, E Jeffrey; Artoni, Andrea; Carassale, Laura; Cazzato, Anna; Ceresini, Graziano; Guralnik, Jack M; Basaria, Shehzad; Valenti, Giorgio; Ferrucci, Luigi

2007-11-12

Aging in men is characterized by a progressive decline in levels of anabolic hormones, such as testosterone, insulinlike growth factor 1 (IGF-1), and dehydroepiandrosterone sulfate (DHEA-S). We hypothesized that in older men a parallel age-associated decline in bioavailable testosterone, IGF-1, and DHEA-S secretion is associated with higher mortality independent of potential confounders. Testosterone, IGF-1, DHEA-S, and demographic features were evaluated in a representative sample of 410 men 65 years and older enrolled in the Aging in the Chianti Area (InCHIANTI) study. A total of 126 men died during the 6-year follow-up. Thresholds for lowest-quartile definitions were 70 ng/dL (to convert to nanomoles per liter, multiply by 0.0347) for bioavailable testosterone, 63.9 ng/mL (to convert to nanomoles per liter, multiply by 0.131) for total IGF-1, and 50 microg/dL (to convert to micromoles per liter, multiply by 0.027) for DHEA-S. Men were divided into 4 groups: no hormone in the lowest quartile (reference) and 1, 2, and 3 hormones in the lowest quartiles. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Compared with men with levels of all 3 hormones above the lowest quartiles, having 1, 2, and 3 dysregulated hormones was associated with hazard ratios for mortality of 1.47 (95% confidence interval [CI], 0.88-2.44), 1.85 (95% CI, 1.04-3.30), and 2.29 (95% CI, 1.12-4.68), respectively (test for trend, P <.001). In the fully adjusted analysis, only men with 3 anabolic hormone deficiencies had a significant increase in mortality (hazard ratio, 2.44; 95% CI, 1.09-5.46 (test for trend, P <.001). Age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men. Having multiple hormonal deficiencies rather than a deficiency in a single anabolic hormone is a robust biomarker of health status in older persons.

Relationship Between Low Levels of Anabolic Hormones and 6-Year Mortality in Older Men

PubMed Central

Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo; Bandinelli, Stefania; Ling, Shari M.; Metter, Jeffrey E.; Artoni, Andrea; Carassale, Laura; Cazzato, Anna; Ceresini, Graziano; Guralnik, Jack M.; Basaria, Shehzad; Valenti, Giorgio; Ferrucci, Luigi

2009-01-01

Background Aging in men is characterized by a progressive decline in levels of anabolic hormones, such as testosterone, insulinlike growth factor 1 (IGF-1), and dehydroepiandrosterone sulfate (DHEA-S). We hypothesized that in older men a parallel age-associated decline in bioavailable testosterone, IGF-1, and DHEA-S secretion is associated with higher mortality independent of potential confounders. Methods Testosterone, IGF-1, DHEA-S, and demographic features were evaluated in a representative sample of 410 men 65 years and older enrolled in the Aging in the Chianti Area (InCHIANTI) study. A total of 126 men died during the 6-year follow-up. Thresholds for lowest-quartile definitions were 70 ng/dL (to convert to nanomoles per liter, multiply by 0.0347) for bioavailable testosterone, 63.9 ng/mL (to convert to nanomoles per liter, multiply by 0.131) for total IGF-1, and 50 μg/dL (to convert to micromoles per liter, multiply by 0.027) for DHEA-S. Men were divided into 4 groups: no hormone in the lowest quartile (reference) and 1, 2, and 3 hormones in the lowest quartiles. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Results Compared with men with levels of all 3 hormones above the lowest quartiles, having 1, 2, and 3 dysregulated hormones was associated with hazard ratios for mortality of 1.47 (95% confidence interval [CI], 0.88-2.44), 1.85 (95% CI, 1.04-3.30), and 2.29 (95% CI, 1.12-4.68), respectively (test for trend, P <.001). In the fully adjusted analysis, only men with 3 anabolic hormone deficiencies had a significant increase in mortality (hazard ratio, 2.44; 95% CI, 1.09-5.46 (test for trend, P <.001). Conclusions Age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men. Having multiple hormonal deficiencies rather than a deficiency in a single anabolic hormone is a robust biomarker of health status in older persons. PMID:17998499

Developmental effects of androgens in the human brain.

PubMed

Nguyen, T-V

2018-02-01

Neuroendocrine theories of brain development posit that androgens play a crucial role in sex-specific cortical growth, although little is known about the differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico-limbic development and cognition during adolescence. In this context, the National Institutes of Health Study of Normal Brain Development, a longitudinal study of typically developing children and adolescents aged 4-24 years (n=433), offers a unique opportunity to examine the developmental effects of androgens on cortico-limbic maturation and cognition. Using data from this sample, our group found that higher testosterone levels were associated with left-sided decreases in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal cortex, compared to right-sided increases in CTh in somatosensory areas in pre-pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural covariance (considered to reflect structural connectivity) also varied according to testosterone levels, with the testosterone-related brain phenotype predicting higher aggression levels and lower executive function, particularly in boys. By contrast, DHEA was associated with a pre-pubertal increase in CTh of several regions involved in cognitive control in both boys and girls. Covariance within several cortico-amygdalar structural networks also varied as a function of DHEA levels, with the DHEA-related brain phenotype predicting improvements in visual attention in both boys and girls. DHEA-related cortico-hippocampal structural covariance, on the other hand, predicted higher scores on a test of working memory. Interestingly, there were significant interactions between testosterone and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of testosterone on brain structure. In sum, testosterone-related effects on the developing brain may lead to detrimental effects on cortical functions (ie, higher aggression and lower

The dark side of creativity: biological vulnerability and negative emotions lead to greater artistic creativity.

PubMed

Akinola, Modupe; Mendes, Wendy Berry

2008-12-01

Historical and empirical data have linked artistic creativity to depression and other affective disorders. This study examined how vulnerability to experiencing negative affect, measured with biological products, and intense negative emotions influenced artistic creativity. The authors assessed participants' baseline levels of an adrenal steroid (dehydroepiandrosterone-sulfate, or DHEAS), previously linked to depression, as a measure of affective vulnerability. They then manipulated emotional responses by randomly assigning participants to receive social rejection or social approval or to a nonsocial situation. Participants then completed artistic collages, which were later evaluated by artists. Results confirmed a person-by-situation interaction. Social rejection was associated with greater artistic creativity; however, the interaction between affective vulnerability (lower baseline DHEAS) and condition was significant, suggesting that situational triggers of negative affect were especially influential among those lower in DHEAS, which resulted in the most creative products. These data provide evidence of possible biological and social pathways to artistic creativity.

The Dark Side of Creativity: Biological Vulnerability and Negative Emotions Lead to Greater Artistic Creativity

PubMed Central

Akinola, Modupe; Mendes, Wendy Berry

2009-01-01

Historical and empirical data have linked artistic creativity to depression and other affective disorders. This study examined how vulnerability to experiencing negative affect, measured with biological products, and intense negative emotions influenced artistic creativity. The authors assessed participants' baseline levels of an adrenal steroid (dehydroepiandrosterone-sulfate, or DHEAS), previously linked to depression, as a measure of affective vulnerability. They then manipulated emotional responses by randomly assigning participants to receive social rejection or social approval or to a nonsocial situation. Participants then completed artistic collages, which were later evaluated by artists. Results confirmed a person-by-situation interaction. Social rejection was associated with greater artistic creativity; however, the interaction between affective vulnerability (lower baseline DHEAS) and condition was significant, suggesting that situational triggers of negative affect were especially influential among those lower in DHEAS, which resulted in the most creative products. These data provide evidence of possible biological and social pathways to artistic creativity. PMID:18832338

Hot Water Bathing Impairs Training Adaptation in Elite Teen Archers.

PubMed

Hung, Ta-Cheng; Liao, Yi-Hung; Tsai, Yung-Shen; Ferguson-Stegall, Lisa; Kuo, Chia-Hua; Chen, Chung-Yu

2018-04-30

Despite heat imposes considerable physiological stress to human body, hot water immersion remains as a popular relaxation modality for athletes. Here we examined the lingering effect of hot tub relaxation after training on performance-associated measures and dehydroepiandrosterone sulfate (DHEA-S) in junior archers. Ten national level archers, aged 16.6 ± 0.3 years (M = 8, F = 2), participated in a randomized counter-balanced crossover study after baseline measurements. In particular, half participants were assigned to the hot water immersion (HOT) group, whereas another halves were assigned to the untreated control (CON) group. Crossover trial was conducted following a 2-week washout period. During the HOT trial, participants immersed in hot water for 30 min at 40°C, 1 h after training, twice a week (every 3 days) for 2 weeks. Participants during CON trial sat at the same environment without hot water after training. Performance-associated measures and salivary DHEA-S were determined 3 days after the last HOT session. We found that the HOT intervention significantly decreased shooting performance (CON: -4%; HOT: -22%, P < 0.05), postural stability (CON: +15%; HOT: -16%, P < 0.05), and DHEA-S levels (CON: -3%; HOT: -60%, P < 0.05) of archers, compared with untreated CON trial. No group differences were found in motor unit recruitment (root mean square electromyography, RMS EMG) of arm muscles during aiming, autonomic nervous activity (sympathetic and vagal powers of heart rate variability, HRV), and plasma cortisol levels after treatments. Our data suggest that physiological adaptation against heat exposure takes away the sources needed for normal training adaptation specific to shooting performance in archers.

[Number of teeth and hormonal profile of postmenopausal women with osteoporosis, osteopenia and normal bone mineral density--a preliminary study].

PubMed

Stagraczyński, Maciej; Kulczyk, Tomasz; Leszczyński, Piotr; Męczekalski, Błażej

2015-10-01

Profound hypoestrogenism causes increased risk of osteoporosis and bone fracture in menopause. This period of women life is also characterized by decrease number of teeth and deterioration of oral cavity health. The aim of the study was to assess the number of teeth, hormonal profile (Follicle-stimualting hormone (FSH), estradiol (E2), testosterone (T) and dehydroepiandrosterone sulphate (DHEA-S) and the bone mineral density (BMD) of the lumbar part of the spine in postmenopausal women with osteoporosis, osteopenia and normal BMD. The next step of the study was to determine whether there was a correlation between vertebral mineral bone density, the hormonal profile and the number of teeth. A total number of 47 women was involved in the study. Based on the results of densitometry tests (DEXA) of vertebral column the subjects were divided into 3 groups: 10 with osteoporosis, 20 with osteopenia and 17 with normal BMD. All the subjects had undergone a hormonal assessment which included blood serum estimation for FSH, E2, DHEA-S and T levels. Also the total number of teeth present was recorded. Serum estradiol and testosterone levels in postmenopausal women were found to be positively correlated with the number of teeth present. A negative correlation was found between age and the number of maxillary teeth in postmenopausal women with osteopenia. There was no influence of serum FSH, estradiol, testosterone and DHEA-S levels on vertebral BMD loss in postmenopausal women. There was no correlation between teeth number and BMD of vertebral column. Serum levels of estradiol and testosterone in postmenopausal women positively correlate with teeth numbers. Age is the main risk factor for teeth loss in postmenopausal women. © 2015 MEDPRESS.

Salivary Biomarker Levels and Diurnal Variation: Associations with Medications Prescribed to Control Children's Problem Behavior

ERIC Educational Resources Information Center

Hibel, Leah C.; Granger, Douglas A.; Cicchetti, Dante; Rogosch, Fred

2007-01-01

This study examined associations between medications prescribed to control children's problem behaviors and levels of, and diurnal variation in, salivary cortisol (C), testosterone (T), and dehydroepiandrosterone (DHEA). Saliva was collected in the morning, midday, and afternoon from 432 children ages 6-13 years. Relative to a no-medication…

Display activity and seasonality of faecal sexual steroids in male great bustard (Otis tarda L.).

PubMed

Biczó, A; Péczely, P

2007-03-01

The non-invasive faecal sampling and RIA was used to measure faecal equivalents of testosterone (T), dehydroepiandrosterone (DHEA), oestradiol-17beta (E2) and progesterone (P4) in juvenile and adult great bustard males. Possible connections of diurnal and seasonal changes of sexual steroid levels and display activity were studied. Correlations were found between sexual steroid equivalent levels of faeces and display activity and agonistic behaviour in the different phases of annual cycle of adult males. In early display period increasing levels of androgens were measured, during main display period very high androgen dominance was observable against E2 and P4. During postnuptial moult strong T decrease and DHEA and P4 increase were detected. Elevation of E2 was measured during wintering. In juveniles level of DHEA was higher than level of T suggesting its importance in immature males. Decrease of T was detected between reproductive period and postnuptial moult and DHEA between reproduction and wintering, accompanying with E2 elevation. The inhibiting effect of inclement weather on gonad functions also was detected in our study. We suppose that the unexpected cold weather with strong wind depressed the levels of androgens both in juveniles and adults and the increase of faecal E2 was also detected.

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.

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.

The association between skeletal maturation and adrenal androgen levels in obese children and adolescents.

PubMed

Kim, Sung Eun; Jang, Joon Weon; Ahn, Moon Bae; Kim, Shin-Hee; Cho, Won Kyoung; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byoung Kyu

2017-06-01

This study aimed to investigate the association between skeletal maturation and adrenal androgen levels in obese children and adolescents. Fifty-three children and adolescents (aged 7-15 years) diagnosed as obese or overweight were investigated. Anthropometric measurements, bone age (BA) determination, serum biochemical analyses, and hormonal measurements were performed. The difference between BA and chronological age (BA-CA, dBACA) was calculated and used to represent the degree of advanced skeletal maturation. Thirty-one subjects were classified into the obese group and 22 subjects into the overweight group. Insulin resistance as calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly higher in the obese group than in the overweight group (4.03±2.20 vs. 2.86±1.11, P =0.026). The skeletal maturation of the obese group was advanced, but the dBACA did not differ between the obese and overweight groups statistically (1.43±1.35 vs. 0.91±1.15, P =0.141). Serum dehydroepiandrosterone sulfate (DHEA-S) levels were significantly higher in subjects with dBACA>1 compared to those with dBACA≤1 (104.3±62.2 vs. 59.6±61.0, P =0.014). Correlation analyses demonstrated that dBACA was positively correlated with body mass index standard deviation scores ( r =0.35, P =0.010), fasting insulin ( r =0.36, P =0.009), HOMA-IR ( r =0.30, P =0.031), and insulin-like growth factor-binding protein-3 ( r =0.331, P =0.028). In multivariate linear regression analysis, HOMA-IR ( P =0.026) and serum DHEA-S ( P =0.032) were positively correlated with the degree of advanced skeletal maturation. Advanced skeletal maturation is associated with increased insulin resistance and elevated DHEA-S levels in obese children and adolescents.

The association between skeletal maturation and adrenal androgen levels in obese children and adolescents

PubMed Central

Kim, Sung Eun; Jang, Joon Weon; Ahn, Moon Bae; Kim, Shin-Hee; Cho, Won Kyoung; Cho, Kyoung Soon; Park, So Hyun; Suh, Byoung Kyu

2017-01-01

Purpose This study aimed to investigate the association between skeletal maturation and adrenal androgen levels in obese children and adolescents. Methods Fifty-three children and adolescents (aged 7–15 years) diagnosed as obese or overweight were investigated. Anthropometric measurements, bone age (BA) determination, serum biochemical analyses, and hormonal measurements were performed. The difference between BA and chronological age (BA–CA, dBACA) was calculated and used to represent the degree of advanced skeletal maturation. Results Thirty-one subjects were classified into the obese group and 22 subjects into the overweight group. Insulin resistance as calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly higher in the obese group than in the overweight group (4.03±2.20 vs. 2.86±1.11, P=0.026). The skeletal maturation of the obese group was advanced, but the dBACA did not differ between the obese and overweight groups statistically (1.43±1.35 vs. 0.91±1.15, P=0.141). Serum dehydroepiandrosterone sulfate (DHEA-S) levels were significantly higher in subjects with dBACA>1 compared to those with dBACA≤1 (104.3±62.2 vs. 59.6±61.0, P=0.014). Correlation analyses demonstrated that dBACA was positively correlated with body mass index standard deviation scores (r=0.35, P=0.010), fasting insulin (r=0.36, P=0.009), HOMA-IR (r=0.30, P=0.031), and insulin-like growth factor-binding protein-3 (r=0.331, P=0.028). In multivariate linear regression analysis, HOMA-IR (P=0.026) and serum DHEA-S (P=0.032) were positively correlated with the degree of advanced skeletal maturation. Conclusion Advanced skeletal maturation is associated with increased insulin resistance and elevated DHEA-S levels in obese children and adolescents. PMID:28690989

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

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

Poulin, R.; Poirier, D.; Merand, Y.

1989-06-05

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

Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea.

PubMed

Miller, K K; Lawson, E A; Mathur, V; Wexler, T L; Meenaghan, E; Misra, M; Herzog, D B; Klibanski, A

2007-04-01

Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. We conducted a cross-sectional study at a general clinical research center. A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether

Circulating Levels of Hormones, Lipids, and Immune Mediators in Post-Traumatic Stress Disorder – A 3-Month Follow-Up Study

PubMed Central

Jergović, Mladen; Bendelja, Krešo; Savić Mlakar, Ana; Vojvoda, Valerija; Aberle, Neda; Jovanovic, Tanja; Rabatić, Sabina; Sabioncello, Ante; Vidović, Anđelko

2015-01-01

A number of peripheral blood analytes have been proposed as potential biomarkers of post-traumatic stress disorder (PTSD). Few studies have investigated whether observed changes in biomarkers persist over time. The aim of this study was to investigate the association of combat-related chronic PTSD with a wide array of putative PTSD biomarkers and to determine reliability of the measurements, i.e., correlations over time. Croatian combat veterans with chronic PTSD (n = 69) and age-matched healthy controls (n = 32), all men, were assessed at two time points separated by 3 months. Serum levels of lipids, cortisol, dehydroepiandrosterone-sulfate (DHEA-S), prolactin, and C-reactive protein were determined. Multiplex assay was used for the simultaneous assessment of 13 analytes in sera: cytokines [interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, TNF-α], adhesion molecules (sPECAM-1, sICAM-1), chemokines (IL-8 and MIP-1α), sCD40L, nerve growth factor, and leptin. Group differences and changes over time were tested by parametric or non-parametric tests, including repeated measures analysis of covariance. Reliability estimates [intraclass correlation coefficient (ICC) and kappa] were also calculated. Robust associations of PTSD with higher levels of DHEA-S [F(1,75) = 8.14, p = 0.006)] and lower levels of prolactin [F(1,75) = 5.40, p = 0.023] were found. Measurements showed good to excellent reproducibility (DHEA-S, ICC = 0.50; prolactin, ICC = 0.79). Serum lipids did not differ between groups but significant increase of LDL-C after 3 months was observed in the PTSD group (t = 6.87, p < 0.001). IL-8 was lower in the PTSD group (t = 4.37, p < 0.001) but assessments showed poor reproducibility (ICC = −0.08). Stable DHEA-S and prolactin changes highlight their potential to be reliable markers of PTSD. Change in lipid profiles after 3 months suggests that PTSD patients may be more prone to hyperlipidemia. High

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

PubMed

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

2016-05-01

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

Causes, Patterns, and Severity of Androgen Excess in 1205 Consecutively Recruited Women.

PubMed

Elhassan, Yasir S; Idkowiak, Jan; Smith, Karen; Asia, Miriam; Gleeson, Helena; Webster, Rachel; Arlt, Wiebke; O'Reilly, Michael W

2018-03-01

Androgen excess in women is predominantly due to underlying polycystic ovary syndrome (PCOS). However, there is a lack of clarity regarding patterns and severity of androgen excess that should be considered predictive of non-PCOS pathology. We examined the diagnostic utility of simultaneous measurement of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone (T) to delineate biochemical signatures and cutoffs predictive of non-PCOS disorders in women with androgen excess. Retrospective review of all women undergoing serum androgen measurement at a large tertiary referral center between 2012 and 2016. Serum A4 and T were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased serum androgen underwent phenotyping by clinical notes review. In 1205 women, DHEAS, A4, and T were measured simultaneously. PCOS was the most common diagnosis in premenopausal (89%) and postmenopausal women (29%). A4 was increased in all adrenocortical carcinoma (ACC) cases (n = 15) and T in all ovarian hyperthecosis (OHT) cases (n = 7); all but one case of congenital adrenal hyperplasia (CAH; n = 18) were identified by increased levels of A4 and/or T. In premenopausal women, CAH was a prevalent cause of severe A4 (59%) and T (43%) excess; severe DHEAS excess was predominantly due to PCOS (80%). In postmenopausal women, all cases of severe DHEAS and A4 excess were caused by ACC and severe T excess equally by ACC and OHT. Pattern and severity of androgen excess are important predictors of non-PCOS pathology and may be used to guide further investigations as appropriate.

Neurosteroids and self-reported pain in veterans who served in the U.S. Military after September 11, 2001.

PubMed

Kilts, Jason D; Tupler, Larry A; Keefe, Francis J; Payne, Victoria M; Hamer, Robert M; Naylor, Jennifer C; Calnaido, Rohana P; Morey, Rajendra A; Strauss, Jennifer L; Parke, Gillian; Massing, Mark W; Youssef, Nagy A; Shampine, Lawrence J; Marx, Christine E

2010-10-01

Nearly half of Operation Enduring Freedom/Operation Iraqi Freedom veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABA(A) receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans. We determined serum neurosteroid levels by gas chromatography/mass spectrometry (allopregnanolone, pregnenolone) or radioimmunoassay (dehydroepiandrosterone [DHEA], progesterone, DHEA sulfate [DHEAS]) in 90 male veterans who served in the U.S. military after September 11, 2001. Self-reported pain symptoms were assessed in four areas (low back pain, chest pain, muscle soreness, headache). Stepwise linear regression analyses were conducted to investigate the relationship between pain assessments and neurosteroids, with the inclusion of smoking, alcohol use, age, and history of traumatic brain injury as covariates. Durham VA Medical Center. Allopregnanolone levels were inversely associated with low back pain (P=0.044) and chest pain (P=0.013), and DHEA levels were inversely associated with muscle soreness (P=0.024). DHEAS levels were positively associated with chest pain (P=0.001). Additionally, there was a positive association between traumatic brain injury and muscle soreness (P=0.002). Neurosteroids may be relevant to the pathophysiology of self-reported pain symptoms in this veteran cohort, and could represent future pharmacological targets for pain disorders. Wiley Periodicals, Inc.

Circulating neuroactive C21- and C19-steroids in young men before and after ejaculation.

PubMed

Stárka, L; Hill, M; Havlíková, H; Kancheva, L; Sobotka, V

2006-01-01

Twelve neuroactive and neuroprotective steroids, androgens and androgen precursors i.e. 3alpha,17beta-dihydroxy-5alpha-androstane, 3alpha-hydroxy-5alpha-androstan-17-one, 3alpha-hydroxy-5beta-androstan-17-one, androst-5-ene-3beta,17beta-diol, 3beta,17alpha-dihydroxy-pregn-5-en-20-one (17alpha-hydroxy-pregnenolone), 3beta-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, androst-4-ene-3,17-dione (androstenedione), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), 3beta-hydroxy-pregn-5-en-20-one (pregnenolone), 7alpha-hydroxy-DHEA, and 7beta-hydroxy-DHEA were measured using the GC-MS system in young men before and after ejaculation provoked by masturbation. The circulating level of 17alpha-hydroxypregnenolone increased significantly, whereas the other circulating steroids were not changed at all. This fact speaks against the hypothesis that a drop in the level of neuroactive steroids, e.g. allopregnanolone may trigger the orgasm-related increase of oxytocin, reported by other authors.

Hyperhomocysteinemia Promotes Insulin Resistance and Adipose Tissue Inflammation in PCOS Mice Through Modulating M2 Macrophage Polarization via Estrogen Suppression.

PubMed

Qi, Xinyu; Zhang, Bochun; Zhao, Yue; Li, Rong; Chang, Hsun-Ming; Pang, Yanli; Qiao, Jie

2017-05-01

It has been shown that serum homocysteine (Hcy) levels are higher in women with polycystic ovary syndrome (PCOS). However, the specific role of hyperhomocysteinemia (HHcy) in the development of PCOS has never been reported. Adipose tissue inflammation is featured by the infiltration of macrophages, which plays a critical role in the pathogenesis of glucose and insulin intolerance. In this study, C57BL/6 mice were treated with dehydroepiandrosterone (DHEA) and/or a high methionine diet to induce PCOS and HHcy mice models. We showed that DHEA induced a PCOS-like phenotypes, irregular estrous cycles, weight gain, abnormal sex hormone production, glucose and insulin resistance, and polycystic ovaries. HHcy further intensified the effects DHEA on the metabolic, endocrinal, hormonal, and morphological changes in PCOS-like mice. In addition, HHcy attenuated the DHEA-induced increase in serum estrogen levels in mice. Furthermore, HHcy may exacerbate the insulin resistance in PCOS-like mice, most likely through modulating the macrophage M1/M2 polarization pathways via the suppression of estrogen. Most important, our clinical data showed that there were increases in serum Hcy levels in patients with PCOS. These findings deepen our understanding of the pathological roles of HHcy in the development of PCOS and provide a promising target for PCOS therapy in clinical application. Copyright © 2017 Endocrine Society.

The sigma-1 receptor-Zinc finger protein 179 pathway protects against hydrogen peroxide-induced cell injury

PubMed Central

Su, Tzu-Chieh; Lin, Shu-Hui; Lee, Pin-Tse; Yeh, Shiu-Hwa; Hsieh, Tsung-Hsun; Chou, Szu-Yi; Su, Tsung-Ping; Hung, Jan-Jong; Chang, Wen-Chang; Lee, Yi-Chao; Chuang, Jian-Ying

2017-01-01

The accumulation of reactive oxygen species (ROS) have implicated the pathogenesis of several human diseases including neurodegenerative disorders, stroke, and traumatic brain injury, hence protecting neurons against ROS is very important. In this study, we focused on sigma-1 receptor (Sig-1R), a chaperone at endoplasmic reticulum, and investigated its protective functions. Using hydrogen peroxide (H2O2)-induced ROS accumulation model, we verified that apoptosis-signaling pathways were elicited by H2O2 treatment. However, the Sig-1R agonists, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), reduced the activation of apoptotic pathways significantly. By performing protein-protein interaction assays and shRNA knockdown of Sig-1R, we identified the brain Zinc finger protein 179 (Znf179) as a downstream target of Sig-1R regulation. The neuroprotective effect of Znf179 overexpression was similar to that of DHEAS treatment, and likely mediated by affecting the levels of antioxidant enzymes. We also quantified the levels of peroxiredoxin 3 (Prx3) and superoxide dismutase 2 (SOD2) in the hippocampi of wild-type and Znf179 knockout mice, and found both enzymes to be reduced in the knockout versus the wild-type mice. In summary, these results reveal that Znf179 plays a novel role in neuroprotection, and Sig-1R agonists may be therapeutic candidates to prevent ROS-induced damage in neurodegenerative and neurotraumatic diseases. PMID:26792191

[Effect of whole body cryotherapy on the levels of some hormones in professional soccer players].

PubMed

Korzonek-Szlacheta, Ilona; Wielkoszyński, Tomasz; Stanek, Agata; Swietochowska, Elzbieta; Karpe, Jacek; Sieroń, Aleksander

2007-01-01

The study was undertaken to determine blood serum concentrations of selected steroid hormones (estradiol--E(2), testosterone--T, dehydroepiandrosterone sulfate--DHEA-S) and luteinizing hormone (LH) in professional footballers subjected to whole body cryotherapy. Twenty-two clinically healthy males, mean age 26.7 years, were studied. The subjects underwent ten sessions of whole body cryotherapy in Wroclaw-type chamber, with kinesitherapy following each session. Blood samples were collected before and two days after the treatment and the results were analyzed statistically. After the treatment there was a significant decrease in the concentrations of T (6.01 vs. 4.80 ng/mL, p < 0.01) and E(2) (102.3 vs. 47.5 pg/mL, p < 0.00001), but no DHEA-S and LH. The T/E(2) ratio showed a significant increase form 72.2 to 136.5 (p < 0.01). Whole body cryotherapy leads to a significant decrease in serum T and E(2), with no effect on LH and DHEAS levels. As a results of cryotherapy, the T/E(2) ratio was significant increased. The changes observed are probably due to cryotherapy-induced alternation in the blood supply to the skin and subcutaneous tissue, as well as to modulation of the activity of aromatase which is responsible for conversion of testosterone and androstenedione to estrogens.

Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine β-synthase-mediated homocysteine metabolism.

PubMed

Li, Da; Liu, Hong-Xiang; Fang, Yuan-Yuan; Huo, Jia-Ning; Wu, Qi-Jun; Wang, Tian-Ren; Zhou, Yi-Ming; Wang, Xiu-Xia; Ma, Xiao-Xin

2018-05-22

What are the metabolic characteristics of homocysteine in polycystic ovary syndrome (PCOS)? Homocysteine concentrations were determined in serum samples from non-obese and obese control subjects and PCOS patients. Homocysteine metabolism was studied in a rat model of PCOS established using dehydroepiandrosterone (DHEA) or DHEA in combination with a high-fat diet (HFD). It was shown that (i) serum homocysteine concentrations were greater in PCOS patients than in control subjects in the obese group (P < 0.05) and serum homocysteine concentrations were significantly higher in the obese group than in the non-obese group, regardless of PCOS status (both P < 0.05); (ii) serum homocysteine concentrations were significantly increased in DHEA + HFD-induced rats compared with controls (P < 0.05); (iii) when compared with the control group, mRNA concentrations of homocysteine metabolic enzymes Bhmt and Cbs were significantly reduced in the liver tissues of DHEA + HFD-induced rats (both P < 0.0001); (iv) when compared with the control group, there was a significant decrease in the methylation concentrations of the Cbs (P < 0.05) and Bhmt (P < 0.05 and P < 0.0001) promoter in the DHEA + HFD group. The methylation patterns, together with previous data, indicate that hypomethylated promoter-mediated transcriptional activation of Bhmt and Cbs might be a defence mechanism against PCOS-related hyperhomocysteinemia. These findings indicate that decreased liver Bhmt and Cbs-mediated homocysteine metabolism might have a role in hyperhomocysteinemia in PCOS and provides further evidence for a potential role of decreased liver function in PCOS. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Androgen Supplementation During Aging: Development of a Physiologically Appropriate Protocol

PubMed Central

Sorwell, Krystina G.; Garyfallou, Vasilios T.; Garten, Jamie; Weiss, Alison; Renner, Laurie; Neuringer, Martha; Kohama, Steven G.

2014-01-01

Abstract Men show an age-related decline in the circulating levels of testosterone (T) and dehydroepiandrosterone sulfate (DHEAS). Consequently, there is interest in developing androgen supplementation paradigms for old men that replicate the hormone profiles of young adults. In the present study, we used old (21–26 years old) male rhesus monkeys as a model to examine the efficacy of an androgen supplementation paradigm that comprised oral T administration (12 mg/kg body weight, dissolved in sesame oil/chocolate) in the evening, and two oral DHEA administrations, 3 hr apart (0.04 mg/kg body weight, dissolved in sesame oil/chocolate) in the morning. After 5 days of repeated hormone supplementation, serial blood samples were remotely collected from each animal hourly across the 24-hr day, and assayed for cortisol, DHEAS, T, 5α-dihydrotestosterone (DHT), estrone (E1), and 17β-estradiol (E2). Following androgen supplementation, T levels were significantly elevated and this was associated with a more sustained nocturnal elevation of T's primary bioactive metabolites, DHT and E1 and E2. Plasma DHEAS levels were also significantly elevated after androgen supplementation; DHEAS levels rose in the early morning and gradually declined during the course of the day, closely mimicking the profiles observed in young adults (7–12 years old); in contrast, cortisol levels were unaltered by the supplementation. Together the data demonstrate a non-invasive androgen supplementation paradigm that restores youthful circulating androgen levels in old male primates. Because this paradigm preserves the natural circulating circadian hormone patterns, we predict that it will produce fewer adverse side effects, such as perturbed sleep or cognitive impairment. PMID:24134213

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.

Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military After September 11, 2001

PubMed Central

Kilts, Jason D; Tupler, Larry A; Keefe, Francis J; Payne, Victoria M; Hamer, Robert M; Naylor, Jennifer C; Calnaido, Rohana P; Morey, Rajendra A; Strauss, Jennifer L; Parke, Gillian; Massing, Mark W; Youssef, Nagy A; Shampine, Lawrence J; Marx, Christine E

2010-01-01

Objective Nearly half of Operation Enduring Freedom / Operation Iraqi Freedom (OEF/OIF) veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABAA receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans. Design We determined serum neurosteroid levels by gas chromatography / mass spectrometry (allopregnanolone, pregnenolone) or radioimmunoassay (dehydroepiandrosterone [DHEA], progesterone, DHEA sulfate [DHEAS]) in 90 male veterans who served in the U.S. military after September 11, 2001. Self-reported pain symptoms were assessed in four areas (low back pain, chest pain, muscle soreness, headache). Stepwise linear regression analyses were conducted to investigate the relationship between pain assessments and neurosteroids, with the inclusion of smoking, alcohol use, age, and history of traumatic brain injury as covariates. Setting Durham VA Medical Center. Results Allopregnanolone levels were inversely associated with low back pain (p=0.044) and chest pain (p=0.013), and DHEA levels were inversely associated with muscle soreness (p=0.024). DHEAS levels were positively associated with chest pain (p=0.001). Additionally, there was a positive association between traumatic brain injury and muscle soreness (p=0.002). Conclusions Neurosteroids may be relevant to the pathophysiology of self-reported pain symptoms in this veteran cohort, and could represent future pharmacological targets for pain disorders. PMID:20735755

The Effects of Sleep Deprivation on Dissociation and Profiles of Mood, and Its Association with Biochemical Changes

PubMed Central

SELVİ, Yavuz; KILIÇ, Sultan; AYDIN, Adem; GÜZEL ÖZDEMİR, Pınar

2015-01-01

Introduction Sleep deprivation is a method, which has being used in order to comprehend the functions of sleep both in healthy individuals and for the patients of depression with in treatment, for a long time. The objective of our present study is to examine the relation between hormonal values, which are known for being related to the effects of these said changes determined in the mood, dissociation and thought suppression in healthy individuals after one night of sleep deprivation implementation. Methods One night sleep deprivation was performed on a total of thirty-two healthy volunteers (16 males and 16 females) who were included in the study. Blood samples were taken from the individuals before and after sleep deprivation implementation in order to determine cortisol, dehydroepiandrosterone-sulfate (DHEA-S) and Thyroid Functions’ Levels tests. In order to evaluate the effects of the sleep deprivation on moods, “White Bear Suppression Inventory (WBSI)” has been conducted, with an aim of evaluating thought suppression, “Profile of Mood States (POMS)”, “Dissociative Experiences Scale (DES)” with a purpose of realizing any dissociation tendency. Results On the individuals who have been implemented for sleep deprivation, a decrease on depression and vigor-activity sub-scales values was detected, and an increase was determined on fatigue sub-scales values of “POMS”. While the values of DES were found to have been statistically increased after sleep deprivation, also a significant decrease was determined on WBSI values. Even if there hasn’t been any significant statistical change determined on cortisol levels after sleep deprivation, yet there had been some significant changes detected on Thyroid Stimulating Hormone (TSH), fT3, fT4, and DHEA-S levels. Decrease in “POMS” depression sub-scale values and increase on fatigue sub-scale values were determined on the individuals whose sT4 levels were found to be increased significantly in statistic

Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4-month randomised trial in middle-aged men.

PubMed

Kjaer, Thomas Nordstrøm; Ornstrup, Marie Juul; Poulsen, Morten Møller; Jørgensen, Jens Otto Lunde; Hougaard, David Michael; Cohen, Arieh Sierra; Neghabat, Shadman; Richelsen, Bjørn; Pedersen, Steen Bønløkke

2015-09-01

Resveratrol is a naturally occurring polyphenol with purported inhibitory effects on prostate growth and cancer development. A number of studies have demonstrated that resveratrol reduces prostate growth in animal models and reduces prostate cell growth in vitro. Based on these pre-clinical findings, interest in resveratrol is increasing in relation to the management of benign prostate hyperplasia (BPH) and prostate cancer. So far, no human trials have evaluated the effects of resveratrol on circulating androgens, prostate size, or biochemical markers of prostate size. In a randomized placebo controlled clinical study using two doses of resveratrol (150 mg or 1,000 mg resveratrol daily) for 4 months, we evaluated the effects on prostate size, prostate specific antigen (PSA) and sex steroid hormones in 66 middle-aged men suffering from the metabolic syndrome(MetS). At baseline, prostate size and PSA were positively correlated (R = 0.34, P < 0.007) as was prostate size and age (R = 0.37, P < 0.003). Prostate size did not correlate with testosterone, free testosterone, dihydrotestosterone (DHT), or any other androgen precursor at baseline. The highest dose of resveratrol lowered the serum level of androstenedione 24% (P = 0.052), dehydroepiandrosterone (DHEA) 41% (P < 0.01), and dehydroepiandrosterone-sulphate (DHEAS) 50% (p<0.001), compared to the control group. However, prostate size and levels of PSA, testosterone, free testosterone and DHT remained unchanged. In this population of middle-aged men suffering from MetS, high dose resveratrol (1,000 mg daily) administration for 4 months significantly lowered serum levels of the androgen precursors androstenedione, DHEA and DHEAS, whereas prostate size and circulating levels of PSA, testosterone, free testosterone, and dihydrotestosterone were unaffected. The present study suggests that resveratrol does not affect prostate volume in healthy middle-aged men as measured by PSA levels and CT acquired prostate volumes

Screening for hypothalamic–pituitary–adrenal axis suppression in asthmatic children remains problematic: a cross-sectional study

PubMed Central

Zöllner, Ekkehard Werner; Lombard, Carl J; Galal, Ushma; Hough, Stephen; Irusen, Elvis M; Weinberg, Eugene

2013-01-01

Objective To determine which parameter is the most useful screening test for hypothalamic–pituitary–adrenal suppression in asthmatic children. Design Cross-sectional study. Setting Paediatric allergy clinics in Cape Town, South Africa. Participants 143 asthmatic children of mostly mixed ancestry, aged 5–12 years. Outcome measures Primary outcome measures included Spearman correlation coefficients (r) calculated between the postmetyrapone (PMTP) serum adrenocorticotropic hormone (ACTH), 11-deoxycortisol (11DOC), 11DOC+ cortisol (C) and height, weight, height velocity, weight velocity, change in systolic blood pressure from supine to standing, early morning urinary free cortisol (UFC), morning C, ACTH and dehydroepiandrosterone sulfate (DHEAS). Secondary outcome measures were the receiver operating characteristics (ROC) curve and the diagnostic statistics for the most promising test. Results All screening variables were weakly correlated with the three PMTP outcomes. Only DHEAS and UFC (nmol/m2) were statistically significant—DHEAS for PMTP ACTH and 11DOC (r=0.20, p=0.025 and r=0.21, p=0.017); UFC (nmol/m2) for PMTP 11DOC and 11DOC+C (r=0.19, p=0.033 and r=0.20, p=0.022). The area under ROC curve for DHEAS in the 5-year to 9-year age group was 0.69 (95% CI 0.47 to 0.92). At DHEAS cut-off of 0.2 µmol/L: sensitivity=0.88 (CI 0.47 to 1.00), specificity=0.61 (CI 0.42 to 0.78), positive predictive value=0.37 (CI 0.16 to 0.62), negative predictive value=0.95 (CI 0.75 to 1.00), accuracy=0.67 (CI 0.50 to 0.81), positive likelihood ratio=2.26 (CI 1.35 to 3.78), negative likelihood ratio=0.20 (CI 0.03 to 1.30). Conclusions No parameter is useful as a universal screening test. DHEAS may be suitable to exclude HPAS before adrenarche. Further research is needed to confirm these findings and identify factors, for example, genetic that may predict or protect against HPAS. PMID:23906954

Leuprolide acetate-stimulated androgen response during female puberty.

PubMed

Hernandez, María Isabel; Martinez-Aguayo, Alejandro; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Mericq, Veronica

2015-08-01

A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. Prospective study of healthy girls (6-12 years) from the local community (n = 63). Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 μg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with

Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation.

PubMed

Rose, K; Allan, A; Gauldie, S; Stapleton, G; Dobbie, L; Dott, K; Martin, C; Wang, L; Hedlund, E; Seckl, J R; Gustafsson, J A; Lathe, R

2001-06-29

The major adrenal steroid dehydroepiandrosterone (DHEA) enhances memory and immune function but has no known dedicated receptor; local metabolism may govern its activity. We described a cytochrome P450 expressed in brain and other tissues, CYP7B, that catalyzes the 7alpha-hydroxylation of oxysterols and 3beta-hydroxysteroids including DHEA. We report here that CYP7B mRNA and 7alpha-hydroxylation activity are widespread in rat tissues. However, steroids related to DHEA are reported to be modified at positions other than 7alpha, exemplified by prominent 6alpha-hydroxylation of 5alpha-androstane-3beta,17beta-diol (A/anediol) in some rodent tissues including brain. To determine whether CYP7B is responsible for these and other activities we disrupted the mouse Cyp7b gene by targeted insertion of an IRES-lacZ reporter cassette, placing reporter enzyme activity (beta-galactosidase) under Cyp7b promoter control. In heterozygous mouse brain, chromogenic detection of reporter activity was strikingly restricted to the dentate gyrus. Staining did not exactly reproduce the in situ hybridization expression pattern; post-transcriptional control is inferred. Lower level staining was detected in cerebellum, liver, and kidney, and which largely paralleled mRNA distribution. Liver and kidney expression was sexually dimorphic. Mice homozygous for the insertion are viable and superficially normal, but ex vivo metabolism of DHEA to 7alpha-hydroxy-DHEA was abolished in brain, spleen, thymus, heart, lung, prostate, uterus, and mammary gland; lower abundance metabolites were also eliminated. 7alpha-Hydroxylation of 25-hydroxycholesterol and related substrates was also abolished, as was presumed 6alpha-hydroxylation of A/anediol. These different enzyme activities therefore derive from the Cyp7b gene. CYP7B is thus a major extrahepatic steroid and oxysterol hydroxylase and provides the predominant route for local metabolism of DHEA and related molecules in brain and other tissues.

Androgens in Women with Anorexia Nervosa and Normal-Weight Women with Hypothalamic Amenorrhea

PubMed Central

Miller, K. K.; Lawson, E. A.; Mathur, V.; Wexler, T. L.; Meenaghan, E.; Misra, M.; Herzog, D. B.; Klibanski, A.

2011-01-01

Context Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Objective Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. Design and Setting We conducted a cross-sectional study at a general clinical research center. Study Participants A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Main Outcome Measures Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Results Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Conclusions Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with

SULT2B1b Sulfotransferase: Induction by Vitamin D Receptor and Reduced Expression in Prostate Cancer

PubMed Central

Seo, Young-Kyo; Mirkheshti, Nooshin; Song, Chung S.; Kim, Soyoung; Dodds, Sherry; Ahn, Soon C.; Christy, Barbara; Mendez-Meza, Rosario; Ittmann, Michael M.; Abboud-Werner, Sherry

2013-01-01

An elevated tumor tissue androgen level, which reactivates androgen receptor in recurrent prostate cancer, arises from the intratumor synthesis of 5α-dihydrotestosterone through use of the precursor steroid dehydroepiandrosterone (DHEA) and is fueled by the steroidogenic enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD1), aldoketoreductase (AKR1C3), and steroid 5-alpha reductase, type 1 (SRD5A1) present in cancer tissue. Sulfotransferase 2B1b (SULT2B1b) (in short, SULT2B) is a prostate-expressed hydroxysteroid SULT that converts cholesterol, oxysterols, and DHEA to 3β-sulfates. DHEA metabolism involving sulfonation by SULT2B can potentially interfere with intraprostate androgen synthesis due to reduction of free DHEA pool and, thus, conversion of DHEA to androstenedione. Here we report that in prostatectomy specimens from treatment-naive patients, SULT2B expression is markedly reduced in malignant tissue (P < .001, Mann-Whitney U test) compared with robust expression in adjacent nonmalignant glands. SULT2B was detected in formalin-fixed specimens by immunohistochemistry on individual sections and tissue array. Immunoblotting of protein lysates of frozen cancer and matched benign tissue confirmed immunohistochemistry results. An in-house–developed rabbit polyclonal antibody against full-length human SULT2B was validated for specificity and used in the analyses. Ligand-activated vitamin D receptor induced the SULT2B1 promoter in vivo in mouse prostate and increased SULT2B mRNA and protein levels in vitro in prostate cancer cells. A vitamin D receptor/retinoid X receptor-α–bound DNA element (with a DR7 motif) mediated induction of the transfected SULT2B1 promoter in calcitriol-treated cells. SULT2B knockdown caused an increased proliferation rate of prostate cancer cells upon stimulation by DHEA. These results suggest that the tumor tissue SULT2B level may partly control prostate cancer growth, and its induction in a therapeutic setting may inhibit disease

Comparative Evaluation of Plasma Bile Acids, Dehydroepiandrosterone Sulfate, Hexadecanedioate, and Tetradecanedioate with Coproporphyrins I and III as Markers of OATP Inhibition in Healthy Subjects.

PubMed

Shen, Hong; Chen, Weiqi; Drexler, Dieter M; Mandlekar, Sandhya; Holenarsipur, Vinay K; Shields, Eric E; Langish, Robert; Sidik, Kurex; Gan, Jinping; Humphreys, W Griffith; Marathe, Punit; Lai, Yurong

2017-08-01

Multiple endogenous compounds have been proposed as candidate biomarkers to monitor organic anion transporting polypeptide (OATP) function in preclinical species or humans. Previously, we demonstrated that coproporphyrins (CPs) I and III are appropriate clinical markers to evaluate OATP inhibition and recapitulate clinical drug-drug interactions (DDIs). In the present study, we investigated bile acids (BAs) dehydroepiandrosterone sulfate (DHEAS), hexadecanedioate (HDA), and tetradecanedioate (TDA) in plasma as endogenous probes for OATP inhibition and compared these candidate probes to CPs. All probes were determined in samples from a single study that examined their behavior and their association with rosuvastatin (RSV) pharmacokinetics after administration of an OATP inhibitor rifampin (RIF) in healthy subjects. Among endogenous probes examined, RIF significantly increased maximum plasma concentration ( C max ) and area under the concentration-time curve (AUC) (0-24h) of fatty acids HDA and TDA by 2.2- to 3.2-fold. For the 13 bile acids in plasma examined, no statistically significant changes were detected between treatments. Changes in plasma DHEAS did not correlate with OATP1B inhibition by RIF. On the basis of the magnitude of effects for the endogenous compounds that demonstrated significant changes from baseline over interindividual variations, the overall rank order for the AUC change was found to be CP I > CP III > HDA ≈ TDA ≈ RSV > > BAs. Collectively, these results reconfirmed that CPs are novel biomarkers suitable for clinical use. In addition, HDA and TDA are useful for OATP functional assessment. Since these endogenous markers can be monitored in conjunction with pharmacokinetics analysis, the CPs and fatty acid dicarboxylates, either alone or in combination, offer promise of earlier diagnosis and risk stratification for OATP-mediated DDIs. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Hormones and Human and Nonhuman Primate Growth.

PubMed

Bernstein, Robin Miriam

2017-01-01

The aim of this paper was to review information pertaining to the hormonal regulation of nonhuman primate growth, with specific focus on the growth hormone (GH)-insulin-like growth factor (IGF) axis and adrenal androgens. Hormones of the GH-IGF axis are consistently associated with measures of growth - linear, weight, or both - during the growth period; in adulthood, concentrations of IGF-I, IGF-binding protein-3, and GH-binding protein are not associated with any measures of size. Comparing patterns of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may be especially relevant for understanding whether the childhood stage of growth and development is unique to humans and perhaps other apes. Genetic, hormonal, and morphological data on adrenarche in other nonhuman primate species suggest that this endocrine transition is delayed in humans, chimpanzees, and possibly gorillas, while present very early in postnatal life in macaques. This suggests that although perhaps permitted by an extension of the pre-adolescent growth period, childhood builds upon existing developmental substrates rather than having been inserted de novo into an ancestral growth trajectory. Hormones can provide insight regarding the evolution of the human growth trajectory. © 2017 S. Karger AG, Basel.

Evaluation of the acceptability of intravaginal prasterone ovule administration using an applicator.

PubMed

Montesino, Marlene; Labrie, Fernand; Archer, David F; Zerhouni, Jaâfar; Côté, Isabelle; Lavoie, Lyne; Beauregard, Adam; Martel, Céline; Vaillancourt, Mario; Moyneur, Erick; Balser, John

2016-01-01

The objective of the study is to evaluate the acceptability of the intravaginal administration of ovules/suppositories of DHEA (dehydroepiandrosterone, prasterone) for the treatment of vulvovaginal atrophy (VVA) in women with moderate to severe dyspareunia who were administered daily for 12 weeks intravaginal 0.50% (6.5 mg) DHEA or placebo. There were a total of 373 women in the per-protocol population who responded to the questionnaire for both treatment groups. While it was planned that the applicator would be evaluated as suitable if at least 80% of participants have a global score  ≤ 2 units, 99% and 100% of participants had a score  ≤ 2 units in the placebo and DHEA groups, respectively, for the global score (mean of 5 questions). When asked about like and dislike the technique of drug administration, 284 comments were positive, while 114 women gave no comment. About 92-94% of women indicated that they were very confident to be able use the applicator successfully in the future. The survey shows a high degree of satisfaction and of confidence to use the applicator successfully in the future.

Steroid and sterol 7-hydroxylation: ancient pathways.

PubMed

Lathe, Richard

2002-11-01

B-ring hydroxylation is a major metabolic pathway for cholesterols and some steroids. In liver, 7 alpha-hydroxylation of cholesterols, mediated by CYP7A and CYP39A1, is the rate-limiting step of bile acid synthesis and metabolic elimination. In brain and other tissues, both sterols and some steroids including dehydroepiandrosterone (DHEA) are prominently 7 alpha-hydroxylated by CYP7B. The function of extra-hepatic steroid and sterol 7-hydroxylation is unknown. Nevertheless, 7-oxygenated cholesterols are potent regulators of cell proliferation and apoptosis; 7-oxygenated derivatives of DHEA, pregnenolone, and androstenediol can have major effects in the brain and in the immune system. The receptor targets involved remain obscure. It is argued that B-ring modification predated steroid evolution: non-enzymatic oxidation of membrane sterols primarily results in 7-oxygenation. Such molecules may have provided early growth and stress signals; a relic may be found in hydroxylation at the symmetrical 11-position of glucocorticoids. Early receptor targets probably included intracellular sterol sites, some modern steroids may continue to act at these targets. 7-Hydroxylation of DHEA may reflect conservation of an early signaling pathway.

The effect of the steroid sulfatase inhibitor (p-O-sulfamoyl)-tetradecanoyl tyramine (DU-14) on learning and memory in rats with selective lesion of septal-hippocampal cholinergic tract.

PubMed

Babalola, P A; Fitz, N F; Gibbs, R B; Flaherty, P T; Li, P-K; Johnson, D A

2012-10-01

Dehydroepiandrosterone sulfate (DHEAS), is an excitatory neurosteroid synthesized within the CNS that modulates brain function. Effects associated with augmented DHEAS include learning and memory enhancement. Inhibitors of the steroid sulfatase enzyme increase brain DHEAS levels and can also facilitate learning and memory. This study investigated the effect of steroid sulfatase inhibition on learning and memory in rats with selective cholinergic lesion of the septo-hippocampal tract using passive avoidance and delayed matching to position T-maze (DMP) paradigms. The selective cholinergic immunotoxin 192 IgG-saporin (SAP) was infused into the medial septum of animals and then tested using a step-through passive avoidance paradigm or DMP paradigm. Peripheral administration of the steroid sulfatase inhibitor, DU-14, increased step-through latency following footshock in rats with SAP lesion compared to both vehicle treated control and lesioned animals (p<0.05). However, in the DMP task, steroid sulfatase inhibition impaired acquisition in lesioned rats while having no effect on intact animals. These results suggest that steroid sulfatase inhibition facilitates memory associated with contextual fear, but impairs acquisition of spatial memory tasks in rats with selective lesion of the septo-hippocampal tract. Copyright © 2012 Elsevier Inc. All rights reserved.

Hypogonadism and erectile dysfunction associated with soy product consumption.

PubMed

Siepmann, Timo; Roofeh, Joseph; Kiefer, Florian W; Edelson, David G

2011-01-01

Previous research has focused on the beneficial effects of soy and its active ingredients, isoflavones. For instance, soy consumption has been associated with lower cardiovascular and breast cancer risks. However, the number of reports demonstrating adverse effects of isoflavones due to their estrogenlike properties has increased. We present the case of a 19-y-old type 1 diabetic but otherwise healthy man with sudden onset of loss of libido and erectile dysfunction after the ingestion of large quantities of soy-based products in a vegan-style diet. Blood levels of free and total testosterone and dehydroepiandrosterone (DHEA) were taken at the initial presentation for examination and continuously monitored up to 2 y after discontinuation of the vegan diet. Blood concentrations of free and total testosterone were initially decreased, whereas DHEA was increased. These parameters normalized within 1 y after cessation of the vegan diet. Normalization of testosterone and DHEA levels was paralleled by a constant improvement of symptoms; full sexual function was regained 1 y after cessation of the vegan diet. This case indicates that soy product consumption is related to hypogonadism and erectile dysfunction. To the best of our knowledge, this is the first report of a combination of decreased free testosterone and increased DHEA blood concentrations after consuming a soy-rich diet. Hence, this case emphasizes the impact of isoflavones in the regulation of sex hormones and associated physical alterations. Copyright © 2011 Elsevier Inc. All rights reserved.

Inverse correlation between morning plasma cortisol levels and MMPI psychasthenia and depression scale scores in victims of mobbing with adjustment disorders.

PubMed

Rocco, Antonio; Martocchia, Antonio; Frugoni, Patrizia; Baldini, Rossella; Sani, Gabriele; Di Simone Di Giuseppe, Barbara; Vairano, Andrea; Girardi, Paolo; Monaco, Edoardo; Tatarelli, Roberto; Falaschi, Paolo

2007-10-01

Evidence in the literature suggests stress-related changes of hypothalamus-pituitary-adrenal (HPA) axis in mobbing. We investigated the association between HPA activity and psychological profiles in mobbing, using a multidisciplinary approach. Forty-eight victims of mobbing were evaluated by a working group of the Departments of Occupational Medicine, Psychiatry and Internal Medicine. After an informed consent, a detailed occupational history, a psychiatric interview with Minnesota Multiphasic Personality Inventory 2 (MMPI-2) administration and a blood sample (8:00 AM) for the determination of basal adrenocorticotropin (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS) plasma levels were collected. Twenty-six patients received an overnight dexamethasone (dex) test. Mean ACTH, cortisol and DHEAS levels were within normal ranges. The dex-test response was normal, with a significant hormone suppression (ACTH p<0.001, cortisol p<0.001, DHEAS p<0.001). The correlations between basal hormones and the psychometric scales of MMPI-2 revealed that cortisol was significantly and negatively related to Psychasthenia (Pt, p=0.003) and Depression (D, p=0.006), while DHEAS showed a significant negative correlation to Hysteria (Hy, p=0.008). Basal ACTH levels were not significantly related to psychometric scales. A significant inverse correlation between morning plasma cortisol levels and psychometric parameters in victims of mobbing with adjustment disorders was observed. A larger group of patients is necessary to identify and validate a cut-off cortisol level that may become an innovative biological parameter for the diagnosis and follow-up in victims of mobbing.

Hypocholesterolemic efficacy of royal jelly in healthy mild hypercholesterolemic adults.

PubMed

Chiu, Hui-Fang; Chen, Bo-Kai; Lu, Yan-Ying; Han, Yi-Chun; Shen, You-Cheng; Venkatakrishnan, Kamesh; Golovinskaia, Oksana; Wang, Chin-Kun

2017-12-01

Royal jelly (RJ) has been reported for its health promoting factors such as antioxidant, anti-inflammatory and lipid lowering activities. The present randomized, placebo-controlled study examines the hypolipidemic beneficial effect of RJ through evaluating anthropometric measurements, lipid profile and various hormone levels in mildly hypercholesterolemic participants. Forty subjects with mild hypercholesterolemia (180-200 mg/dL) were randomly selected and divided into two groups as experimental or placebo, who requested to intake nine capsules (350 mg/capsule) of RJ or placebo/day, respectively, for three months with one month of follow-up without any supplementation. No significant changes were noted in any of the anthropometric parameters like body weight, waist and body fat. The serum total cholesterol (TC; 207.05-183.15 mg/dL) and low-density lipoprotein cholesterol (LDL-c; 126.44-120.31 mg/dL) levels were reduced significantly (p < 0.05) after administration of RJ. However, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-c) levels were not considerably altered. Moreover, three months of RJ consumption significantly ameliorated (p < 0.05) the concentration of sex hormones like dehydroepiandrosterone sulphate (DHEA-S; 1788.09-1992.31 ng/mL). Also, intake of RJ did not elicit any hepatic or renal damage. Intervention with RJ for three months considerably lowered the TC and LDL-c levels through improving the levels of DHEA-S and thus alleviates the risk of cardiovascular disease (CVD).

Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat.

PubMed

Qaiser, M Zeeshan; Dolman, Diana E M; Begley, David J; Abbott, N Joan; Cazacu-Davidescu, Mihaela; Corol, Delia I; Fry, Jonathan P

2017-09-01

Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found 3 H-PregS to enter more rapidly than 3 H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes. Although permeability measurements suggested a net efflux, addition of the efflux inhibitors GF120918 and/or MK571 to the perfusate reduced rather than enhanced the uptake of 3 H-DHEAS and 3 H-PregS; a further reduction was seen upon the addition of unlabelled steroid sulphate, suggesting a saturable uptake transporter. Analysis of brain fractions after 0.5 min perfusion with the 3 H-steroid sulphates showed no further metabolism of PregS beyond the liberation of free steroid pregnenolone. By contrast, DHEAS underwent 17-hydroxylation to form androstenediol in both the steroid sulphate and the free steroid fractions, with some additional formation of androstenedione in the latter. Our results indicate a gain of free steroid from circulating steroid sulphates as hormone precursors at the blood-brain barrier, with implications for ageing, neurogenesis, neuronal survival, learning and memory. © 2017 International Society for Neurochemistry.

Psychobiological stress in vital exhaustion. Findings from the Men Stress 40+ study.

PubMed

Noser, Emilou; Fischer, Susanne; Ruppen, Jessica; Ehlert, Ulrike

2018-02-01

Despite the increased risk for cardiovascular morbidity associated with vital exhaustion (VE), the underlying pathophysiological mechanisms remain unclear. Allostatic load may constitute the missing link between VE and cardiovascular diseases. The aim of the present study was to investigate whether men with different degrees of VE would differ in terms of allostatic load, chronic stress, and social support. The Men Stress 40+ study sample consisted of N=121 apparently healthy men aged 40 to 75years. The following allostatic load markers were aggregated to create a cumulative index of biological stress: salivary cortisol, salivary dehydroepiandrosterone sulfate (DHEA-S), waist-to-hip-ratio, systolic and diastolic blood pressure. Long-term cortisol and DHEA were additionally measured in hair. Chronic stress and social support were assessed via validated questionnaires. Groups of mildly, substantially, and severely exhausted men were compared using one-way ANOVAs with appropriate post-hoc tests. Men who reported mild or severe levels of vital exhaustion had the highest scores on the cumulative index of biological stress. Hair cortisol was unrelated to vital exhaustion; hair DHEA was highest in men with substantial levels of exhaustion. Men with mild exhaustion reported the lowest levels of chronic stress, while men with severe exhaustion reported the lowest levels of social support. Signs of allostatic load are detectable in vitally exhausted men at a stage where no major cardiovascular consequences have yet ensued. Copyright © 2017 Elsevier Inc. All rights reserved.

A New Model for Adrenarche: Inhibition of 3β-Hydroxysteroid Dehydrogenase Type 2 by Intra-Adrenal Cortisol.

PubMed

Majzoub, Joseph A; Topor, Lisa Swartz

2018-05-30

We propose that the normal adrenarche-related rise in dehydroepiandrosterone (DHEA) secretion is ultimately caused by the rise in cortisol production occurring during childhood and adolescent growth, by the following mechanisms. (1) The onset of childhood growth leads to a slight fall in serum cortisol concentration due to growth-induced dilution and a decrease in the negative feedback of cortisol upon ACTH secretion. (2) In response, ACTH rises and stimulates increased cortisol synthesis and secretion in the growing body to restore the serum cortisol concentration to normal. (3) The cortisol concentration produced within and taken up by adrenocortical steroidogenic cells may rise during this time. (4) Cortisol competitively inhibits 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2)-mediated conversion of 17αOH-pregnenolone to cortisol, causing a further fall in serum cortisol, a further decrease in the negative feedback of cortisol upon ACTH, a further rise in ACTH, and further stimulation of adrenal steroidogenesis. (5) The cortisol-mediated inhibition of 3βHSD2 also blocks the conversion of DHEA to androstenedione, causing a rise in adrenal DHEA and DHEA sulfate relative to androstenedione secretion. Thus, the combination of normal body growth plus inhibition of 3βHSD2 by intra-adrenal cortisol may cause normal adrenarche. Childhood obesity may hasten this process by causing a pathologic increase in body size that triggers these same processes at an earlier age, resulting in the premature onset of adrenarche. © 2018 S. Karger AG, Basel.

Genetic polymorphisms, hormone levels, and hot flashes in midlife women.

PubMed

Schilling, Chrissy; Gallicchio, Lisa; Miller, Susan R; Langenberg, Patricia; Zacur, Howard; Flaws, Jodi A

2007-06-20

Hot flashes disrupt the lives of millions of women each year. Although hot flashes are a public health concern, little is known about risk factors that predispose women to hot flashes. Thus, the objective of this study was to examine whether sex steroid hormone levels and genetic polymorphisms in hormone biosynthesis and degradation enzymes are associated with the risk of hot flashes. In a cross-sectional study design, midlife women aged 45-54 years (n=639) were recruited from Baltimore and its surrounding counties. Participants completed a questionnaire and donated a blood sample for steroid hormone analysis and genotyping. The associations between genetic polymorphisms and hormone levels, as well as the associations between genetic polymorphisms, hormone levels, and hot flashes were examined using statistical models. A polymorphism in CYP1B1 was associated with lower dehydroepiandrosterone-sulfate (DHEA-S) and progesterone levels, while a polymorphism in CYP19 (aromatase) was associated with higher testosterone and DHEA-S levels. Lower progesterone and sex hormone binding globulin levels, lower free estradiol index, and a higher ratio of total androgens to total estrogens were associated with the experiencing of hot flashes. A polymorphism in CYP1B1 and a polymorphism in 3betaHSD were both associated with hot flashes. Some genetic polymorphisms may be associated with altered levels of hormones in midlife women. Further, selected genetic polymorphisms and altered hormone levels may be associated with the risk of hot flashes in midlife women.

Adrenocortical reserves in hyperthyroidism.

PubMed

Agbaht, Kemal; Gullu, Sevim

2014-02-01

Explicit data regarding the changes in adrenocortical reserves during hyperthyroidism do not exist. We aimed to document the capability (response) of adrenal gland to secrete cortisol and DHEA-S during hyperthyroidism compared to euthyroidism, and to describe factors associated with these responses. A standard-dose (0.25 mg/i.v.) ACTH stimulation test was performed to the same patients before hyperthyroidism treatment, and after attainment of euthyroidism. Baseline cortisol (Cor(0)), DHEA-S (DHEA-S(0)), cortisol binding globulin (CBG), ACTH, calculated free cortisol (by Coolen's equation = CFC), free cortisol index (FCI), 60-min cortisol (Cor(60)), and DHEA-S (DHEA-S(60)), delta cortisol (ΔCor), delta DHEA-S (ΔDHEA-S) responses were evaluated. Forty-one patients [22 females, 49.5 ± 15.2 years old, 32 Graves disease, nine toxic nodular goiter] had similar Cor(0), DHEA-S(0), CFC, FCI, and DHEA-S(60) in hyperthyroid and euthyroid states. Cor(60), ΔCor, and ΔDHEA-S were lower in hyperthyroidism. In four (10 %) patients the peak ACTH-stimulated cortisol values were lower than 18 μg/dL. When the test repeated after attainment of euthyroidism, all of the patients had normal cortisol response. Regression analysis demonstrated an independent association of Cor(60) with free T3 in hyperthyroidism. However, the predictors of CFC, FCI, and DHEA-S levels were serum creatinine levels in hyperthyroidism, and both creatinine and transaminase levels in euthyroidism. ACTH-stimulated peak cortisol, delta cortisol, and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover. Since about 10 % of the subjects with hyperthyroidism are at risk for adrenal insufficiency, clinicians dealing with Graves' disease should be alert to the possibility of adrenal insufficiency during hyperthyroid stage.

Characterization and longitudinal monitoring of serum androgens and glucocorticoids during normal pregnancy in the killer whale (Orcinus orca).

PubMed

Robeck, Todd R; Steinman, Karen J; O'Brien, Justine K

2017-06-01

The secretory patterns of testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEA), cortisol (C), and corticosterone (Co) were characterized throughout 28 normal pregnancies until two-months post-partum in eleven killer whales. Effects of fetal sex, dam parity or age, and season were evaluated across either day post-conception (DPC), stage of pregnancy (PRE, EARLY, MID, LATE, POST) or indexed month post-conception (IMPC) using a mixed model linear regression with animal ID and pregnancy number as the random variables. Across DPC, DHEA, A4 and T concentrations were affected (P<0.05) by season, with highest concentrations during spring (DHEA, A4, & T) and summer (A4) as compared to the fall. A significant effect of parity on androgen production was observed only for DHEA, with multiparous females having higher (P=0.01) concentrations than nulliparous females. All three androgens significantly increased with each successive pregnancy stage and IMPC with peak concentrations occurring during IMPC 10 (DHEA), 13 (A4) and 14 (T), respectively. Cortisol was affected by season (P=0.03) with highest concentrations being detected during the months of fall, while Co was only affected by parity (P=0.003) with significant increases observed for primiparous females as compared to nulliparous females. Cortisol and Co concentrations peaked (P<0.05) during IMPC 17 (i.e., the month prior to parturition). The C to Co ratio during pregnancy was 7.4 to 1, indicating that cortisol is the major circulating glucocorticoid studied to date in pregnant killer whales. The significant increase in concentrations of maternal androgens throughout pregnancy, which were unrelated to fetal sex, indicates that they play an important role during killer whale fetal development. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of neuroactive steroids on cochlear hair cell death induced by gentamicin.

PubMed

Nakamagoe, Mariko; Tabuchi, Keiji; Nishimura, Bungo; Hara, Akira

2011-12-11

As neuroactive steroids, sex steroid hormones have non-reproductive effects. We previously reported that 17β-estradiol (βE2) had protective effects against gentamicin (GM) ototoxicity in the cochlea. In the present study, we examined whether the protective action of βE2 on GM ototoxicity is mediated by the estrogen receptor (ER) and whether other estrogens (17α-estradiol (αE2), estrone (E1), and estriol (E3)) and other neuroactive steroids, dehydroepiandrosterone (DHEA) and progesterone (P), have similar protective effects. The basal turn of the organ of Corti was dissected from Sprague-Dawley rats and cultured in a medium containing 100 μM GM for 48h. The effects of βE2 and ICI 182,780, a selective ER antagonist, were examined. In addition, the effects of other estrogens, DHEA and P were tested using this culture system. Loss of outer hair cells induced by GM exposure was compared among groups. βE2 exhibited a protective effect against GM ototoxicity, but its protective effect was antagonized by ICI 182,780. αE2, E1, and E3 also protected hair cells against gentamicin ototoxicity. DHEA showed a protective effect; however, the addition of ICI 182,780 did not affect hair cell loss. P did not have any effect on GM-induced outer hair cell death. The present findings suggest that estrogens and DHEA are protective agents against GM ototoxicity. The results of the ER antagonist study also suggest that the protective action of βE2 is mediated via ER but that of DHEA is not related to its conversion to estrogen and binding to ER. Further studies on neuroactive steroids may lead to new insights regarding cochlear protection. Copyright © 2011 Elsevier Inc. All rights reserved.

Hypoandrogenism in association with diminished functional ovarian reserve.

PubMed

Gleicher, Norbert; Kim, Ann; Weghofer, Andrea; Kushnir, Vitaly A; Shohat-Tal, Aya; Lazzaroni, Emanuela; Lee, Ho-Joon; Barad, David H

2013-04-01

Is diminished functional ovarian reserve (DFOR) associated with low androgen levels? Low androgen levels are associated with DFOR at all ages. Androgen supplementation via dehydroepiandrosterone (DHEA) has been reported to improve functional ovarian reserve (FOR); pregnancy rates in IVF cycles are associated with how well DHEA converts to testosterone (T); and androgen effects through the androgen receptor have been demonstrated in mice to beneficially affect early stages of follicle maturation. In a controlled cohort study we investigated consecutive women presenting to our center with two forms of DFOR, premature ovarian aging/occult primary ovarian insufficiency (POA/OPOI) and physiologic diminished ovarian reserve (DOR). As controls for POA/OPOI patients, infertile women with normal age-specific FOR were recruited. The study involved 140 women with POA/OPOI, defined as age <38 years and abnormally low FOR by age-specific FSH and/or anti-Müllerian hormone (AMH), 166 women with DOR, defined as women age >40 years. Forty-nine control patients <38 years demonstrated normal FOR by FSH and/or AMH. In all three patient groups dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), total testosterone (TT) and free testosterone (FT) at the time of initial presentation to our fertility center were assessed. In a small subgroup of women early morning cortisol levels were also assessed. DHEAS marginally varied between the three groups (P = 0.04), with older women with DOR actually demonstrating higher levels than controls (P = 0.03). TT differed between the three groups more profoundly (P = 0.005), with women with POA/OPOI demonstrating significantly lower levels than controls (P = 0.009). Adjustment for body mass index, age and race in principle maintained observed differences in TT between groups, while adjustment for FMR1 (fragile X mental retardation 1) genotypes/sub-genotypes eliminated all differences. All three patient groups demonstrated low morning cortisol levels

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

PubMed

Goh, Victor H H; Tong, Terry Y Y

2011-07-01

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

Relationships between plasma and erythrocyte Zn and maturation in adolescent males

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

Arquitt, A.B.; Hermann, J.R.; Stoecker, B.J.

Sixty-three male volunteers between the ages of 10.6 and 14.3 yr were assessed for maturation and zinc status. The adrenal androgen dehydroepiandrosterone sulfate (DHEAS), used as a maturation indicator, was significantly correlated with height, weight, hemoglobin, and mid-arm muscle area (MAMA) as previously reported. Erythrocyte Zn (RBC-Zn) and plasma Zn were significantly correlated. When grouped by plasma Zn tertiles, significant differences were found for RBC-Zn and cholesterol between the highest and lowest groups. When subjects were grouped by RBC-Zn concentration, the lowest 10% of subjects had higher concentrations of DHEAS, lower plasma Zn , and were taller, heavier and hadmore » larger MAMA than the other group. In these subjects plasma and RBC-Zn concentrations were within normal limits. In this study RBC-Zn and plasma Zn were related to indicators of maturation.« less

A Multifaceted Analysis of Immune-Endocrine-Metabolic Alterations in Patients with Pulmonary Tuberculosis

PubMed Central

Santucci, Natalia; D'Attilio, Luciano; Kovalevski, Leandro; Bozza, Verónica; Besedovsky, Hugo; del Rey, Adriana; Bay, María Luisa; Bottasso, Oscar

2011-01-01

Our study investigated the circulating levels of factors involved in immune-inflammatory-endocrine-metabolic responses in patients with tuberculosis with the aim of uncovering a relation between certain immune and hormonal patterns, their clinical status and in vitro immune response. The concentration of leptin, adiponectin, IL-6, IL-1β, ghrelin, C-reactive protein (CRP), cortisol and dehydroepiandrosterone (DHEA), and the in vitro immune response (lymphoproliferation and IFN-γ production) was evaluated in 53 patients with active untreated tuberculosis, 27 household contacts and 25 healthy controls, without significant age- or sex-related differences. Patients had a lower body mass index (BMI), reduced levels of leptin and DHEA, and increased concentrations of CRP, IL-6, cortisol, IL-1β and nearly significant adiponectin values than household contacts and controls. Within tuberculosis patients the BMI and leptin levels were positively correlated and decreased with increasing disease severity, whereas higher concentrations of IL-6, CRP, IL-1β, cortisol, and ghrelin were seen in cases with moderate to severe tuberculosis. Household contacts had lower DHEA and higher IL-6 levels than controls. Group classification by means of discriminant analysis and the k-nearest neighbor method showed that tuberculosis patients were clearly different from the other groups, having higher levels of CRP and lower DHEA concentration and BMI. Furthermore, plasma leptin levels were positively associated with the basal in vitro IFN-γ production and the ConA-driven proliferation of cells from tuberculosis patients. Present alterations in the communication between the neuro-endocrine and immune systems in tuberculosis may contribute to disease worsening. PMID:22022605

Differences in testosterone and its precursors by sex of the offspring in meconium

PubMed Central

Frey, Alexander J.; Park, Bo Y.; Schriver, Emily R.; Feldman, Daniel R.; Parry, Samuel; Croen, Lisa A.; Fallin, Daniele M.; Hertz-Picciotto, Irva; Newschaffer, Craig J.; Snyder, Nathaniel W.

2016-01-01

Prenatal metabolism exerts profound effects on development. The first stool of the newborn, meconium, provides a window into the prenatal metabolic environment. The objective of this study was to examine the feasibility of meconium as a novel matrix to quantify prenatal steroid levels. We quantified parameters of analytical interest regarding the use of meconium, including sample stability. We hypothesized that meconium steroid content would differ by sex, prompting analysis of meconium to test effects of prenatal steroid metabolism. Meconium from 193 newborns enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) study, including 107 males, and 86 females, were analyzed by isotope dilution-liquid chromatography-high resolution mass spectrometry (ID-LC-HRMS) while blinded to identity for testosterone (T), androstenedione (AD), and dehydroepiandrosterone (DHEA). Steroids levels were compared by sex, and investigations of potential trends resulting from sample storage or processing was conducted. The unconjugated steroid content of meconium in ng/g (mean, standard deviation) was for males: T (2.67, 8.99), AD (20.01, 28.12), DHEA (13.96, 23.57) and for females: T (0.82, 1.63), AD (22.32, 24.38), DHEA (21.06, 43.49). T was higher in meconium from males (p = 0.0333), and DHEA was higher in meconium from females (p = 0.0202). 6 female and 3 male T values were below the limit of detection. No extreme variability in hydration or trend in steroid levels by storage time was detected. Sexually dimorphic levels of hormones may reflect gestational differentiation, and future studies should consider meconium analysis. PMID:27871978

Intrinsic factors rather than vitamin D deficiency are related to insulin resistance in lean women with polycystic ovary syndrome.

PubMed

Sahin, S; Eroglu, M; Selcuk, S; Turkgeldi, L; Kozali, S; Davutoglu, S; Muhcu, M

2014-10-01

To investigate the correlation between insulin resistance (IR) and serum 25-OH-Vit D concentrations and hormonal parameters in lean women with polycystic ovary syndrome (PCOS). 50 lean women with PCOS and 40 body mass index (BMI) matched controls were compared in terms of fasting insulin and glucose, homeostatic model assessment insulin resistance (HOMA-IR), 25-OH-Vit D, high sensitivity C-reactive protein (hs-CRP), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, dehydroepiandrosterone sulfate (DHEA-S), total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides and Ferriman-Gallway (FG) scores. Correlation analyses were performed between HOMA-IR and metabolic and endocrine parameters. 30% of patients with PCOS demonstrated IR. Levels of 25-OH-Vit D, hsCRP, cholesterol, HDL, LDL, triglyceride and fasting glucose did not differ between the study and control groups. Fasting insulin, HOMA-IR, LH, total testosterone, and DHEA-S levels were higher in PCOS group. HOMA-IR was found to correlate with hs-CRP and total testosterone but not with 25-OH-Vit D levels in lean patients with PCOS. An association between 25-OH-Vit D levels and IR is not evident in lean women with PCOS. hs-CRP levels do not indicate to an increased risk of cardiovascular disease in this population of patients. Because a strong association between hyperinsulinemia and hyperandrogenism exists in lean women with PCOS, it is advisable for this population of patients to be screened for metabolic disturbances, especially in whom chronic anovulation and hyperandrogenism are observed together.

Methods for determination of fingernail steroids by LC/MS/MS and differences in their contents between right and left hands.

PubMed

Higashi, Tatsuya; Yamagata, Kenichiro; Kato, Yuina; Ogawa, Yu; Takano, Kaori; Nakaaze, Yutaro; Iriyama, Takashi; Min, Jun Zhe; Ogawa, Shoujiro

2016-05-01

Fingernail clipping is expected to be a specimen for steroid testing, because it has several advantages over blood; i.e., noninvasive collection, ease of storage, portability and handling, and possibility for an assessment of the steroid status over a relatively long and retrospective time window. In this study, we examined whether there is a difference in the nail contents between the right and left hands for five steroids [glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA), dehydroepiandrosterone sulfate (DHEAS), testosterone (TST) and cortisol (CRT)] using newly developed liquid chromatography/electrospray ionization-tandem mass spectrometry methods. The nail contents between the hands were significantly different for GCDCA, TCDCA and DHEAS, whereas those of TST and CRT only slightly differed. These results might be due to the difference in the binding affinity of each steroid for the nail keratin. The relatively hydrophilic steroids, GCDCA, TCDCA and DHEAS, may be lost from nails in daily life due to their low affinity for keratin, which would produce differences in the nail contents between the hands. Thus, the fingernail GCDCA, TCDCA and DHEAS contents may be influenced by factors other than the disease; the nail analysis is inefficient in the diagnosis of the disease associated with these steroids. On the other hand, the nail analysis looks promising for evaluation of the status of TST and CRT, which are lipophilic and inferred to be tightly bound to the keratin. In fact, the nail TST content showed a significant sex difference, just like its serum/plasma concentration. Copyright © 2016 Elsevier Inc. All rights reserved.

Lipid and other plasma markers are associated with anxiety, depression, and fatigue.

PubMed

Lieberman, Harris R; Kellogg, Mark D; Kramer, F Matthew; Bathalon, Gaston P; Lesher, Larry L

2012-03-01

Few peripheral metabolites have been shown to be associated with mood in healthy individuals or patients with central nervous system diseases. During military basic combat training (BCT), mood state, physical performance and body composition substantially improve, providing an opportunity to examine relationships between mood and nutritional and hormonal biomarkers. Thirty-five females enrolled in U.S. Marine BCT, an intense physically and mentally challenging 12-week course, were studied. Every 4 weeks, mood was assessed with the Profile of Mood States (POMS), as were nutritional, metabolic and hormonal plasma markers. Mood and fitness improved over BCT, and there were substantial changes in biochemical markers. Multiple regression demonstrated that, in combination, cholesterol (HDL, LDL), fructosamine, triglycerides, free fatty acids (FFA), dehydroepiandrosterone-sulfate (DHEA-S), ACTH, and substance P accounted for 44% of variation in anxiety, 40% confusion, 37% fatigue, 27% depression and 40% in total mood (p < .0001). Increased HDL, FFA, DHEA-S, and substance P were associated with degraded mood (p < .05). Increased LDL, triglycerides, fructosamine, and ACTH were associated with improved mood (p < .05). Other markers, including glucose, cortisol, and C-reactive protein were not associated with mood. Normal human mood state was associated with 8 plasma markers. Increased HDL and lower LDL, which are associated with improved cardiovascular status, were associated with negative affect. Fructosamine and substance P, not previously known to be related to mood, were associated with it. We are not aware of any biological parameters that in aggregate predict such a substantial proportion of variation in normal mood.

Male Inmate Profiles and Their Biological Correlates

PubMed Central

Horn, Mathilde; Potvin, Stephane; Allaire, Jean-François; Côté, Gilles; Gobbi, Gabriella; Benkirane, Karim; Vachon, Jeanne; Dumais, Alexandre

2014-01-01

Objective: Borderline and antisocial personality disorders (PDs) share common clinical features (impulsivity, aggressiveness, substance use disorders [SUDs], and suicidal behaviours) that are greatly overrepresented in prison populations. These disorders have been associated biologically with testosterone and cortisol levels. However, the associations are ambiguous and the subject of controversy, perhaps because these heterogeneous disorders have been addressed as unitary constructs. A consideration of profiles of people, rather than of exclusive diagnoses, might yield clearer relationships. Methods: In our study, multiple correspondence analysis and cluster analysis were employed to identify subgroups among 545 newly convicted inmates. The groups were then compared in terms of clinical features and biological markers, including levels of cortisol, testosterone, estradiol, progesterone, and sulfoconjugated dehydroepiandrosterone (DHEA-S). Results: Four clusters with differing psychiatric, criminal, and biological profiles emerged. Clinically, one group had intermediate scores for each of the tested clinical features. Another group comprised people with little comorbidity. Two others displayed severe impulsivity, PD, and SUD. Biologically, cortisol levels were lowest in the last 2 groups and highest in the group with less comorbidity. In keeping with previous findings reported in the literature, testosterone was higher in a younger population with severe psychiatric symptoms. However, some apparently comparable behavioural outcomes were found to be related to distinct biological profiles. No differences were observed for estradiol, progesterone, or DHEA-S levels. Conclusions: The results not only confirm the importance of biological markers in the study of personality features but also demonstrate the need to consider the role of comorbidities and steroid coregulation. PMID:25161069

Mutual influences between partners' hormones shape conflict dialog and relationship duration at the initiation of romantic love.

PubMed

Schneiderman, Inna; Kanat-Maymon, Yaniv; Zagoory-Sharon, Orna; Feldman, Ruth

2014-01-01

Early-stage romantic love involves reorganization of neurohormonal systems and behavioral patterns marked by mutual influences between the partners' physiology and behavior. Guided by the biobehavioral synchrony conceptual frame, we tested bidirectional influences between the partners' hormones and conflict behavior at the initiation of romantic love. Participants included 120 new lovers (60 couples) and 40 singles. Plasma levels of five affiliation and stress-related hormones were assessed: oxytocin (OT), prolactin (PRL), testosterone (T), cortisol (CT), and dehydroepiandrosterone sulfate (DHEAS). Couples were observed in conflict interaction coded for empathy and hostility. CT and DHEAS showed direct actor effects: higher CT and DHEAS predicted greater hostility. OT showed direct partner effects: individuals whose partners had higher OT showed greater empathy. T and CT showed combined actor-partner effects. High T predicted greater hostility only when partner also had high T, but lower hostility when partner had low T. Similarly, CT predicted low empathy only in the context of high partner's CT. Mediational analysis indicated that combined high CT in both partners was associated with relationship breakup as mediated by decrease in empathy. Findings demonstrate the mutual influences between hormones and behavior within an attachment bond and underscore the dynamic, co-regulated, and systemic nature of pair-bond formation in humans.

Heterogenous origins of hyperandrogenism in the polycystic ovary syndrome in relation to body mass index and insulin resistance.

PubMed

Patlolla, Shalini; Vaikkakara, Suresh; Sachan, Alok; Venkatanarasu, Ashok; Bachimanchi, Bharath; Bitla, Aparna; Settipalli, Sarala; Pathiputturu, Sumathi; Sugali, Roopa Naik; Chiri, Sravani

2018-03-01

Insulin resistance and obesity are not universal features of polycystic ovary syndrome (PCOS). We planned to assess the differences between patients with nonobese /insulin-sensitive phenotype vs. obese/ insulin-resistant phenotype in terms of the potential mechanisms underlying their hyperandrogenism. A total of 52 women satisfying Androgen Excess Society (AES) criteria were included. Hormonal and metabolic profile including prolactin, dehydroepiandrosterone sulfate (DHEAS), free testosterone, sex hormone binding globulin (SHBG), fasting plasma glucose and insulin were measured in follicular phase. DHEAS was found to be higher in the nonobese patients as compared to the obese (p = 0.01). There was also a strong trend for a higher DHEAS among patients with lower insulin resistance by homeostatic model assessment (HOMA-IR< 2.3) (p = .06).While the total testosterone (p = .044) and SHBG (p = .007) were found to be lower in the more insulin-resistant group (HOMA-IR ≥ 2.3), the free testosterone levels were similar. However, the percentage of free testosterone was higher in the more insulin-resistant group (p = .005). The hyperandrogenic state in PCOS appears to have heterogenous origins. Nonobese patients with PCOS have adrenal hyperandrogenism as the underlying mechanism while their obese/ insulin-resistant counterparts have low SHBG and hence an increased fraction of free testosterone.

Do burned-out and work-engaged employees differ in the functioning of the hypothalamic-pituitary-adrenal axis?

PubMed

Langelaan, Saar; Bakker, Arnold B; Schaufeli, Wilmar B; van Rhenen, Willem; van Doornen, Lorenz J P

2006-10-01

The central aim of the present study was to examine differences in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis between 29 burned-out, 33 work-engaged, and 26 healthy reference managers, as identified with the Maslach Burnout Inventory-General Survey and the Utrecht Work Engagement Scale. All of the managers were employed in a large Dutch telecommunications company. Salivary cortisol was sampled on three consecutive workdays and one nonworkday to determine the cortisol awakening response. Salivary dehydroepiandrosterone-sulfate (DHEAS), a cortisol counterbalancing product of the HPA axis, was measured on these days 1 hour after managers awakened. The dexamethasone suppression test was used to investigate the feedback sensitivity of the HPA axis. The morning cortisol levels were higher on the workdays than on the nonworkday, but this effect did not differ between the three groups. The burned-out, work-engaged, and reference groups did not differ in the cortisol and DHEAS levels, the slope of the cortisol awakening response, and the cortisol : DHEAS ratio. The work-engaged group showed a stronger cortisol suppression in response to the dexamethasone suppression test than the other two groups, the finding suggesting higher feedback sensitivity among work-engaged managers. Burned-out and work-engaged managers only differ marginally in HPA-axis functioning.

Serum lipid levels and steroidal hormones in women runners with irregular menses.

PubMed

Thompson, D L; Snead, D B; Seip, R L; Weltman, J Y; Rogol, A D; Weltman, A

1997-02-01

This study compared the lipid profile of women runners with menstrual cycle irregularities with their normally menstruating counterparts. Relationships among selected steroid hormones and serum lipid levels in 10 eumenorrheic (EU) and 8 oligo-/amenorrheic (O/A) women runners and 6 eumenorrheic controls (CON) were examined. Serum 17 beta-estradiol (E2), progesterone (Prog), and dehydroepiandrosterone-sulfate (DHEAS) concentrations were determined in daily blood samples for 21 days, and integrated concentrations were calculated. Fasting blood samples were analyzed for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL2, HDL3, triglycerides (Trig), and apolipoproteins A-1, A-II, and B. The O/A group had significantly lower E2 and Prog than EU or CON groups. Women in the CON group had lower HDL-C and HDL3 than the runners. With all women grouped together, E2 was not significantly correlated with any measured blood lipid parameters. On the other hand, DHEAS was significantly correlated with HDL-C, HDL2, and apolipoprotein A-I. These data demonstrate that women runners, regardless of menstrual cycle status, exhibit higher HDL-C concentrations than CON and supports previous research reporting a positive association between DHEAS and HDL-C.

Validation of highly sensitive simultaneous targeted and untargeted analysis of keto-steroids by Girard P derivatization and stable isotope dilution-liquid chromatography-high resolution mass spectrometry.

PubMed

Frey, Alexander J; Wang, Qingqing; Busch, Christine; Feldman, Daniel; Bottalico, Lisa; Mesaros, Clementina A; Blair, Ian A; Vachani, Anil; Snyder, Nathaniel W

2016-12-01

A multiplexed quantitative method for the analysis of three major unconjugated steroids in human serum by stable isotope dilution liquid chromatography-high resolution mass spectrometry (LC-HRMS) was developed and validated on a Q Exactive Plus hybrid quadrupole/Orbitrap mass spectrometer. This quantification utilized isotope dilution and Girard P derivatization on the keto-groups of testosterone (T), androstenedione (AD) and dehydroepiandrosterone (DHEA) to improve ionization efficiency using electrospray ionization. Major isomeric compounds to T and DHEA; the inactive epimer of testosterone (epiT), and the metabolite of AD, 5α-androstanedione (5α-AD) were completely resolved on a biphenyl column within an 18min method. Inter- and intra-day method validation using LC-HRMS with qualifying product ions was performed and acceptable analytical performance was achieved. The method was further validated by comparing steroid levels from 100μL of serum from young vs older subjects. Since this approach provides high-dimensional HRMS data, untargeted analysis by age group was performed. DHEA and T were detected among the top analytes most significantly different across the two groups after untargeted LC-HRMS analysis, as well as a number of other still unknown metabolites, indicating the potential for combined targeted/untargeted analysis in steroid analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationships between oral MUC1 expression and salivary hormones in burning mouth syndrome.

PubMed

Kang, Jeong-Hyun; Kim, Yoon-Young; Chang, Ji-Youn; Kho, Hong-Seop

2017-06-01

To investigate possible relationships among oral mucosal epithelial MUC1 expression, salivary female gonadal hormones and stress markers, and clinical characteristics in patients with burning mouth syndrome (BMS). Thirty post-menopausal female patients with BMS (60.0±5.0 years) were included. Clinical and psychological evaluations were performed and the expression level of oral mucosal epithelial MUC1 was analyzed. The levels of cortisol, dehydroepiandrosterone (DHEA), 17β-estradiol, progesterone, chromogranin A, and blood contamination were determined from unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) samples. Salivary progesterone level had significant positive correlations with oral mucosal epithelial MUC1 expression level and with salivary cortisol and DHEA levels. The salivary level of 17β-estradiol showed significant positive correlations with period of symptom duration, severity of effects of oral complaints on daily life, and results from psychological evaluations. Cortisol level in UWS and cortisol/DHEA ratio in UWS and SWS had negative correlations with severity of oral burning sensation significantly. The severity of taste disturbance had positive correlations with results from psychometry significantly. Dysregulated psychoendocrinological interactions might affect oral mucosal MUC1 expression and severity of oral burning sensation in post-menopausal BMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2012-11-20

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

Gene- and environment-dependent neuroendocrine etiogenesis of homosexuality and transsexualism.

PubMed

Dörner, G; Poppe, I; Stahl, F; Kölzsch, J; Uebelhack, R

1991-01-01

Sexual brain organization is dependent on sex hormone and neurotransmitter levels occurring during critical developmental periods. The higher the androgen levels during brain organization, caused by genetic and/or environmental factors, the higher is the biological predisposition to bi- and homosexuality or even transsexualism in females and the lower it is in males. Adrenal androgen excess, leading to heterotypical sexual orientation and/or gender role behavior in genetic females, can be caused by 21-hydroxylase deficiency, especially when associated with prenatal stress. The cortisol (F) precursor 21-deoxycortisol (21-DOF) was found to be significantly increased after ACTH stimulation in homosexual as compared to heterosexual females. 21-DOF was increased significantly before and even highly significantly after ACTH stimulation in female-to-male transsexuals. In view of these data, heterozygous and homozygous forms, respectively, of 21-hydroxylase deficiency represent a genetic predisposition to androgen-dependent development of homosexuality and transsexualism in females. Testicular androgen deficiency in prenatal life, giving rise to heterotypical sexual orientation and/or gender role behavior in genetic males, may be induced by prenatal stress and/or maternal or fetal genetic alterations. Most recently, in mothers of homosexual men--following ACTH stimulation--a significantly increased prevalence of high 21-DOF plasma values and 21-DOF/F ratios was found, which surpassed the mean + 1 SD level of heterosexual control women. In homosexual men as well--following ACTH stimulation--most of the 21-DOF plasma values and 21-DOF/F ratios also surpassed the mean + 1 SD level of heterosexual men. In only one out of 9 homosexual males, neither in his blood nor in that of his mother increased 21-DOF values and 21-DOF/F ratios were found after ACTH stimulation. In this homosexual man, however, the plasma dehydroepiandrosterone sulfate (DHEA-S) values and the DHEA-S/1000 x A

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

PubMed Central

Goh, Victor HH; Tong, Terry YY

2011-01-01

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

Effect of royal jelly ingestion for six months on healthy volunteers.

PubMed

Morita, Hiroyuki; Ikeda, Takahide; Kajita, Kazuo; Fujioka, Kei; Mori, Ichiro; Okada, Hideyuki; Uno, Yoshihiro; Ishizuka, Tatsuo

2012-09-21

Royal jelly is a widely ingested supplement for health, but its effects on humans are not well known. The objective was to evaluate the effects of long-term royal jelly ingestion on humans. We conducted a randomized placebo-controlled, double-blind trial. A total of 61 healthy volunteers aged 42-83 years were enrolled and were randomly divided into a royal jelly group (n = 31) and a control group (n = 30). Three thousand mg of royal jelly (RJ) or a placebo in 100 ml liquid/day were ingested for 6 months. The primary outcomes were changes in anthropometric measurements and biochemical indexes from baseline to 6 months after intervention. Thirty subjects in the RJ group and 26 in the control group were included in the analysis of endpoints. In an adjusted mean change of the variables from the baseline, significant differences between the two groups could be found in red blood cell counts (+0.16x10⁶/μL for the RJ group vs. -0.01x10⁶/μL for the control group, P = 0.0134), hematocrit (+0.9% vs. -0.8%, P = 0.0251), log (fasting plasma glucose) (+0.01 ± 0.01 log mg/dL vs. +0.05 ± 0.01 log mg/dL, P = 0.0297), log (insulinogenic index) (+0.25 vs. -0.13, P = 0.0319), log dehydroepiandrosterone sulfate (DHEA-S) (+0.08 log μg/dL vs. +0.20 log μg/dL, P = 0.0483), log testosterone (T) (+0.12 ± 0.04 log ng/mL vs. -0.02 ± 0.05 log ng/mL, P = 0.0416), log T/DHEA-S ratio (+0.05 ± 0.05 vs. -0.23 ± 0.59, P = 0.0015), and in one of the SF-36 subscale scores, mental health (MH) (+4 vs. -7, P = 0.0276). Six-month ingestion of RJ in humans improved erythropoiesis, glucose tolerance and mental health. Acceleration of conversion from DHEA-S to T by RJ may have been observed among these favorable effects.

Depression, Anxiety, and Anger in Patients with Polycystic Ovary Syndrome.

PubMed

Balikci, Adem; Erdem, Murat; Keskin, Uğur; Bozkurt Zincir, Selma; Gülsün, Murat; Özçelik, Fatih; Akgül, Emin Özgür; Akarsu, Süleyman; Öztosun, Muzaffer; Ergün, Ali

2014-12-01

Polycystic Ovary Syndrome (PCOS) is a syndrome of heterogeneous nature, affecting multiple systems, particularly the endocrine system. We propose to investigate the possible relationships among hormonal changes, levels of anxiety, depression, and anger in patients with PCOS. Forty-four female patients with PCOS and 44 body mass index (BMI )-matched healthy women participated in this study. We measured the sociodemographic features, some serum hormonal levels (insulin, gonadotropins, prolactin, dehydroepiandrosterone sulfate (DHEAS), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), 17 OH-progesterone, and total and free testosterone), and some other biochemical parameters of the participants. Also, all participants completed the Trait Anger-Anger Expression Scale (STAS), Beck Depression, and Beck Anxiety Inventories. We evaluated the psychiatric scale scores obtained from PCOS patients and control subjects. We used the independent-samples t-test for parametric data to evaluate normal distribution, and Mann-Whitney U-test was used for both abnormally distributed and nonparametric data. We used Pearson correlation analysis to evaluate the potential connection between the two groups' data. The mean ages of the patients with PCOS and control subjects who participated in this study were 27.3±5.6 and 27.4±6.1 years, respectively. The measures of BMI, insulin, luteinizing hormone (LH), DHEAS, and total testosterone serum levels in the patient group were significantly higher than in the control group (p<.05). There was a statistically significant positive correlation between Beck anxiety scores and serum DHEAS levels (Pearson r=.4366, P=.0001). We found significant differences between the two groups in terms of trait anger, anger control, outward and inward anger, anxiety level, and depression scores (P<.05). Anxiety symptoms indicate a stronger relationship compared to depression with DHEAS serum levels via the autonomic nervous system

5-AED Enhances Survival of Irradiated Mice in a G-CSF-Dependent Manner, Stimulates Innate Immune Cell Function, Reduces Radiation-induced DNA Damage and Induces Genes that Modulate Cell Cycle Progression and Apoptosis

DTIC Science & Technology

2012-01-01

modulate cell cycle progression and apoptosis. INTRODUCTION Because of the increasing threat posed by nuclear weapons [1], there is a pressing need for both...were per- formed using the iCycler iQ Sequence Detection System ( Bio -Rad Laboratories, Hercules CA) on 96-well microtiter plates with optical caps...Thoss K, Petrow PK et al. Amelioration of murine antigen -induced arthritis by dehydroepiandrosterone (DHEA). Inflamm Res 2004;53:189–98. 56. Auci D

5-AED Enhances Survival of Irradiated Mice in a G-CSF-Dependent Manner, Stimulates Innate Immune Cell Function, Reduces Radiation-Induced DNA Damage and Induces Genes that Modulate Cell Cycle Progression and Apoptosis

DTIC Science & Technology

2012-07-22

modulate cell cycle progression and apoptosis. INTRODUCTION Because of the increasing threat posed by nuclear weapons [1], there is a pressing need for both...Detection System ( Bio -Rad Laboratories, Hercules CA) on 96-well microtiter plates with optical caps. Reactions were performed in a total volume of 50 µL... antigen -induced arthritis by dehydroepiandrosterone (DHEA). Inflamm Res 2004;53:189–98. 56. Auci D, Nicoletti F, Mangano K et al. Anti-inflammatory and

Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

PubMed

Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

2018-05-01

The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P < 0.05). There were 58 (49.2%) cases who did not reach to the embryo transfer stage due to several reasons including cancelation of stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P < 0.001). FSH was a significant predictor for cancelation of stimulation (AUC 0.774, P < 0.001). In women with diminished ovarian reserve, basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

Differences in testosterone and its precursors by sex of the offspring in meconium.

PubMed

Frey, Alexander J; Park, Bo Y; Schriver, Emily R; Feldman, Daniel R; Parry, Samuel; Croen, Lisa A; Fallin, Daniele M; Hertz-Picciotto, Irva; Newschaffer, Craig J; Snyder, Nathaniel W

2017-03-01

Prenatal metabolism exerts profound effects on development. The first stool of the newborn, meconium, provides a window into the prenatal metabolic environment. The objective of this study was to examine the feasibility of meconium as a novel matrix to quantify prenatal steroid levels. We quantified parameters of analytical interest regarding the use of meconium, including sample stability. We hypothesized that meconium steroid content would differ by sex, prompting analysis of meconium to test effects of prenatal steroid metabolism. Meconium from 193 newborns enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) study, including 107 males, and 86 females, were analyzed by isotope dilution-liquid chromatography-high resolution mass spectrometry (ID-LC-HRMS) while blinded to identity for testosterone (T), androstenedione (AD), and dehydroepiandrosterone (DHEA). Steroid levels were compared by sex, and investigations of potential trends resulting from sample storage or processing was conducted. The unconjugated steroid content of meconium in ng/g (mean, standard deviation) was for males: T (2.67, 8.99), AD (20.01, 28.12), DHEA (13.96, 23.57) and for females: T (0.82, 1.63), AD (22.32, 24.38), DHEA (21.06, 43.49). T was higher in meconium from males (p=0.0333), and DHEA was higher in meconium from females (p=0.0202). 6 female and 3 male T values were below the limit of detection. No extreme variability in hydration or trend in steroid levels by storage time was detected. Sexually dimorphic levels of hormones may reflect gestational differentiation, and future studies should consider meconium analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-04-01

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

Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

PubMed

Rossi, Emanuela; Morabito, Alessandro; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; De Maio, Ermelinda; Di Maio, Massimo; Piccirillo, Maria Carmela; De Feo, Gianfranco; D'Aiuto, Giuseppe; Botti, Gerardo; Chiodini, Paolo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2009-07-01

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

Anabolic and catabolic biomarkers as predictors of muscle strength decline: the InCHIANTI study.

PubMed

Stenholm, Sari; Maggio, Marcello; Lauretani, Fulvio; Bandinelli, Stefania; Ceda, Gian Paolo; Di Iorio, Angelo; Giallauria, Francesco; Guralnik, Jack M; Ferrucci, Luigi

2010-02-01

Poor muscle strength is a major public health concern in older persons, predisposing to functional limitations, increased fall risk, and higher mortality. Understanding risk factors for muscle strength decline may offer opportunities for prevention and treatment. One of the possible causes of muscle strength decline is imbalance between catabolic and anabolic signaling. This study aims to examine whether high levels of multiple catabolic and low levels of multiple anabolic biomarkers predict accelerated decline of muscle strength. In a representative sample of 716 men and women aged >or=65 years in the InCHIANTI study we measured C-reactive protein, interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-alpha receptor 1 as well as dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1, and bioavailable testosterone. Biomarker values were divided into tertiles and the numbers of catabolic/anabolic biomarkers in the highest/lowest tertile were calculated. Hand-grip strength was measured at baseline and 3- and 6-year follow up. In adjusted linear mixed models, higher concentration of IL-6 (p = 0.02) and IL-1RA (p = 0.04) as well as lower levels of DHEA-S (p = 0.01) predicted muscle strength decline. After combining all inflammatory markers, the rate of decline in grip strength was progressively greater with the increasing number of dysregulated catabolic biomarkers (p = 0.01). No effect on accelerated muscle strength decline was seen according to number of dysregulated anabolic hormones. Having multiple elevated catabolic biomarkers is a better predictor of muscle strength decline than a single biomarker alone, suggesting that a catabolic dysregulation is at the core of the mechanism leading to muscle strength decline with aging.

Mail-Based Intervention for Sarcopenia Prevention Increased Anabolic Hormone and Skeletal Muscle Mass in Community-Dwelling Japanese Older Adults: The INE (Intervention by Nutrition and Exercise) Study.

PubMed

Yamada, Minoru; Nishiguchi, Shu; Fukutani, Naoto; Aoyama, Tomoki; Arai, Hidenori

2015-08-01

The aim of the Intervention by Nutrition and Exercise (INE) study was to investigate the effects of a mail-based intervention for sarcopenia prevention on muscle mass and anabolic hormones in community-dwelling older adults. A cluster-randomized controlled trial. This trial recruited community-dwelling adults aged 65 years and older in Japan. The 227 participants were cluster randomized into a walking and nutrition (W/N) group (n = 79), a walking (W) group (n = 71), and a control (C) group (n = 77). We analyzed the physical and biochemical measurements in this substudy. Six months of mail-based intervention (a pedometer-based walking program and nutritional supplementation). The skeletal muscle mass index (SMI) using the bioelectrical impedance data acquisition system, biochemical measurements, such as those of insulinlike growth factor (IGF-1), dehydroepiandrosterone sulfate (DHEA-S), and 25-hydroxy vitamin D (25[OH]D), as well as frailty, were assessed by the Cardiovascular Health Study criteria. Participants in the W/N and W groups had significantly greater improvements in SMI, IGF-1, and 25(OH)D (P < .05) than those in the C group. Participants in the W/N group had significantly greater improvements in DHEA-S (P < .05) than in the other groups. These effects were more pronounced in frail, older adults. These results suggest that the mail-based walking intervention of the remote monitoring type for sarcopenia prevention can increase anabolic hormone levels and SMI in community-dwelling older adults, particularly in those who are frail. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Protective Effects of Fetal Zone Steroids Are Comparable to Estradiol in Hyperoxia-Induced Cell Death of Immature Glia.

PubMed

Hübner, Stephanie; Sunny, Donna E; Pöhlke, Christine; Ruhnau, Johanna; Vogelgesang, Antje; Reich, Bettina; Heckmann, Matthias

2017-05-01

Impaired neurodevelopment in preterm infants is caused by prematurity itself; however, hypoxia/ischemia, inflammation, and hyperoxia contribute to the extent of impairment. Because preterm birth is accompanied by a dramatic decrease in 17β-estradiol (E2) and progesterone, preliminary clinical studies have been carried out to substitute these steroids in preterm infants; however, they failed to confirm significantly improved neurologic outcomes. We therefore hypothesized that the persistently high postnatal production of fetal zone steroids [mainly dehydroepiandrosterone (DHEA)] until term could interfere with E2-mediated protection. We investigated whether E2 could reduce hyperoxia-mediated apoptosis in three immature glial cell types and detected the involved receptors. Thereafter, we investigated protection by the fetal zone steroids DHEA, 16α-hydroxy-DHEA, and androstenediol. For DHEA, the involved receptors were evaluated. We examined aromatases, which convert fetal zone steroids into more estrogenic compounds. Finally, cotreatment was compared against single hormone treatment to investigate synergism. In all cell types, E2 and fetal zone steroids resulted in significant dose-dependent protection, whereas the mediating receptors differed. The neuroprotection by fetal zone steroids highly depended on the cell type-specific expression of aromatases, the receptor repertoire, and the potency of the fetal zone steroids toward these receptors. No synergism in fetal zone steroid and E2 cotreatment was detected in two of three cell types. Therefore, E2 supplementation may not be beneficial with respect to neuroprotection because fetal zone steroids circulate in persistently high concentrations until term in preterm infants. Hence, a refined experimental model for preterm infants is required to investigate potential treatments. Copyright © 2017 Endocrine Society.

Anabolic hormone profiles in elite military men: Robust associations with age, stress, and fatigue.

PubMed

Taylor, Marcus K; Padilla, Genieleah A; Hernández, Lisa M

2017-08-01

We recently established stable daily profiles of the anabolic hormones dehydroepiandrosterone (DHEA) and testosterone in 57 elite military men. In this follow-on study, we explored associations of salivary anabolic hormone profiles with demographic (i.e., age, body mass index [BMI]) and biobehavioral health indices (i.e., blood pressure, sleep, perceived stress, fatigue) via correlational models. Next, nuanced patterns were constructed using quartile splits followed by one-way analysis of variance and post hoc subgroup comparisons. Both DHEA (r range: -0.33 to -0.49) and testosterone (r range: -0.19 to -0.41) were inversely associated with age. Quartile comparisons revealed that age-related declines in DHEA were linear, curvilinear, or sigmoidal, depending on the summary parameter of interest. Anabolic hormone profiles did not associate with BMI, blood pressure, or sleep efficiency. Robust linear associations were observed between testosterone and perceived stress (r range: -0.29 to -0.36); concentration-dependent patterns were less discernible. Lower DHEA (r range: -0.22 to -0.30) and testosterone (r range: -0.22 to -0.36) concentrations associated with higher fatigue. Subsequent quartile comparisons suggested a concentration-dependent threshold with respect to evening testosterone. Specifically, those individuals within the lowest quartile (≤68.4pg/mL) endorsed the highest fatigue of the four groups (p=0.01), while the remaining three groups did not differ from each other. This study not only showed that anabolic hormone profiles have distinctive age trajectories, but are also valuable predictors of stress and fatigue in elite military men. This highlights the importance of routine monitoring of anabolic hormone profiles to sustain and optimize health and readiness in chronically stressed populations. Published by Elsevier Inc.

Musculo-skeletal pain, psychological distress, and hormones during the menopausal transition.

PubMed

Finset, Arnstein; Øverlie, Inger; Holte, Arne

2004-01-01

To investigate the relationship between sex hormones (estradiol, testosterone, androstendione, DHEA-S) and prolactin on one hand and musculo-skeletal pain and psychological distress on the other during the menopausal transition. Fifty-seven regularly menstruating women, who were studied over five consecutive years, who reached menopause before the fifth assessment, and did not use hormone replacement therapy were included in the study. Hormones were sampled and a questionnaire including questions on psychological distress and musculo-skeletal pain were administered at the five points of assessment. Data on last year before menopause (T1), first (T2) and second (T3) year after menopause are reported. DHEA-S, but neither testosterone nor androstendione, was inversely related to distress and pain. Pain contributed to the variance of DHEA-S over the menopausal transition, whereas DHEA-S levels did not predict pain or distress when baseline levels were controlled for. Prolactin was at T1 and T2 positively associated with distress and at T2 positively associated with musculo-skeletal pain. Musculo-skeletal pain pre-menopause was significantly related to estradiol. DHEA-S was negatively associated, and prolactin positively associated with musculo-skeletal pain and psychological distress. Whereas post-menopause DHEA-S levels were influenced by pain scores, no significant effect of pre-menopause hormones on post-menopause pain and distress was found.

The effect of high level tennis matches on urine steroid profiles in professional tennis players.

PubMed

Muñoz, D; Toribio, F; Timón, R; Olcina, G; Maynar, J I; Maynar, M

2010-12-01

Modern day, tennis matches are characterized by shorter and more intense efforts with players enduring great physical and psychological stress. The aim of this study was to evaluate acute changes in the urinary steroid profile of elite tennis players following professional tournament matches. Eight professional male tennis players participated in this study. Urine samples were collected before and after tennis matches corresponding to the quarter finals of the Spanish Tennis Masters. After the match, there was a significant fall (P<0.05) in testosterone, androsterone, etiocholanolone, and dehydroepiandrosterone (DHEA). Cortisone increased whereas tetrahydrocortisone (THE) decreased. The anabolic/catabolic hormone ratio also decreased, although only the fall in total suprarenal androgen (TSA)/total corticosteroid (TC) and DHEA/(THE+THF) ratios had a significant decrease (P<0.05). These results indicate that a professional tennis match modifies the urine steroid profiles of players, increasing corticosteroid and decreasing androgen excretion in urine, suggesting an important adrenal activation.

Exhaustion and endocrine functioning in clinical burnout: an in-depth study using the experience sampling method.

PubMed

Sonnenschein, Mieke; Mommersteeg, Paula M C; Houtveen, Jan H; Sorbi, Marjolijn J; Schaufeli, Wilmar B; van Doornen, Lorenz J P

2007-05-01

The current study investigates the relationship between HPA-axis functioning and burnout symptoms by employing an electronic symptom diary. This diary method circumvents the retrospection bias induced by symptom questionnaires and allows to study relationships within-in addition to between-subjects. Forty two clinically burned-out participants completed the exhaustion subscale of the Maslach burnout inventory and kept an electronic diary for 2 weeks to assess momentary exhaustion and daily recovery through sleep. On 3 consecutive weekdays within the diary period, saliva was sampled to determine the cortisol awakening response (CAR), levels of dehydroepiandrosterone-sulphate (DHEAS) on the first 2 weekdays, and to conduct the dexamethasone suppression test (DST) on the third weekday. We found significant relationships between endocrine values and general momentary symptom severity as assessed with the diary, but not with the retrospective questionnaire-assessed burnout symptoms. Simultaneous assessments of endocrine values and burnout symptoms assessed with the diary after awakening rendered significant associations between persons, and a trend within persons. More severe burnout symptoms were consistently associated with a lower level and smaller increase of CAR, higher DHEAS levels, smaller cortisol/DHEAS ratios and a stronger suppression after DST. Burnout symptoms were significantly related to endocrine functioning in clinical burnout under the best possible conditions of symptom measurement. This adds support to the view that severity of burnout symptoms is associated with HPA-axis functioning.

Adrenal steroid hormones and metaphyseal bone in children.

PubMed

Remer, Thomas; Boye, Kai R; Hartmann, Michaela F; Neu, Christina; Schoenau, Eckhard; Manz, Friedrich; Wudy, Stefan A

2004-01-01

The responses of metaphyseal bone tissue to physiological variations of endogenous adrenal steroid hormones during childhood are unclear. Therefore, we studied potential hormonal influences in children before the appearance of pubic hair (onset of pubarche). Excretions of major glucocorticoid metabolites (C21), cortisol, sum of adrenarchal dehydroepiandrosterone and its immediate 16-hydroxylated metabolites (DHEA&M), and 5-androstene-3beta,17beta-diol (hermaphrodiol) were analyzed in a cross-sectional study in 24-hour urine samples of 109 healthy boys and girls, aged 6-13 years, using steroid profiling by gas chromatography-mass spectrometry. Total and trabecular volumetric bone mineral densities, bone mineral content (BMC) and bone strength strain index were determined with peripheral quantitative computed tomography at the distal forearm. In multiple regression analyses significant associations with the metaphyseal radius were seen for grip force, age, or BMI depending on gender and bone variable analyzed. DHEA&M did not contribute to the explanation of the variance of any bone variable. However, hermaphrodiol positively explained a significant part of variation of bone mineral densities, and BMC (p < 0.01) in girls. Significantly negative associations with all bone variables were seen in boys for cortisol. The steroid hormones, cortisol and hermaphrodiol, in their physiological ranges, but not the adrenarche marker DHEA&M, appear to associate with metaphyseal bone in a sex-dependent manner during childhood. Copyright (c) 2004 S. Karger AG, Basel.

Effects of exemestane and tamoxifen on hormone levels within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German substudy.

PubMed

Hadji, P; Kauka, A; Bauer, T; Tams, J; Hasenburg, A; Kieback, D G

2012-10-01

The aim of this study was to compare the effects of exemestane and tamoxifen on hormone levels in postmenopausal patients with hormone receptor-positive breast cancer within a Germany substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Within the TEAM trial, patients were randomized to receive adjuvant treatment with exemestane for 5 years or tamoxifen for 2.5-3 years followed by exemestane for 2-2.5 years. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)-intact were measured at screening and after 3, 6 and 12 months of treatment. Data on hormone levels were available from 63 patients in the tamoxifen arm and 68 patients in the exemestane arm. Treatment with exemestane resulted in decreases from baseline in SHBG and PTH-intact levels, and increases from baseline in testosterone, DHEAS and FSH levels. Tamoxifen treatment resulted in increases from baseline in SHBG and PTH-intact, whereas levels of testosterone and FSH decreased and DHEAS levels did not change. At all time points assessed, the absolute change from baseline was significantly different between tamoxifen and exemestane for testosterone, SHBG, FSH and PTH-intact (all p < 0.0001). Exemestane and tamoxifen had statistically significantly different effects on hormone levels, including testosterone, SHBG, FSH and PTH-intact.

Definition of the Cellular Mechanisms which Distinguish Between Estrogen Receptor Agonists and Antagonists

DTIC Science & Technology

2001-07-01

hormones: 10-7 M 17p3- estradiol for ERa and ERI3, 10-7 M progesterone for PR-A and PR-B, 10-7 M dexamethasone for GR, 10-7 M 5ot-dihydrotestosterone...cyproterone acetate, d-Ald.: d-aldosterone, DHEA: dehydroepiandrosterone, DOC: 11-deoxycorticosterone, Dex: dexamethasone, MPA: medroxyprogesterone , OH-F...two receptors are not functionally equivalent and that tory activities by altering ER structure and indepen- each subtype plays a unique role in ER

Reassessment of the Access Testosterone chemiluminescence assay and comparison with LC-MS method.

PubMed

Dittadi, Ruggero; Matteucci, Mara; Meneghetti, Elisa; Ndreu, Rudina

2018-03-01

To reassess the imprecision and Limit of Quantitation, to evaluate the cross-reaction with dehydroepiandrosterone-sulfate (DHEAS), the accuracy toward liquid chromatography-mass spectrometry (LC-MS) and the reference interval of the Access Testosterone method, performed by DxI immunoassay platform (Beckman Coulter). Imprecision was evaluated testing six pool samples assayed in 20 different run using two reagents lots. The cross-reaction with DHEAS was studied both by a displacement curve and by spiking DHEAS standard in two serum samples with known amount of testosterone. The comparison with LC-MS was evaluated by Passing-Bablock analysis in 21 routine serum samples and 19 control samples from an External Quality Assurance (EQA) scheme. The reference interval was verified by an indirect estimation on 2445 male and 2838 female outpatients. The imprecision study showed a coefficient of variation (CV) between 2.7% and 34.7% for serum pools from 16.3 and 0.27 nmol/L. The value of Limit of Quantitation at 20% CV was 0.53 nmol/L. The DHEAS showed a cross-reaction of 0.0074%. A comparison with LC-MS showed a trend toward a slight underestimation of immunoassay vs LC-MS (Passing-Bablock equations: DxI=-0.24+0.906 LCMS in serum samples and DxI=-0.299+0.981 LCMS in EQA samples). The verification of reference interval showed a 2.5th-97.5th percentile distribution of 6.6-24.3 nmol/L for male over 14 years and <0.5-2.78 nmol/L for female subjects, in accord with the reference intervals reported by the manufacturer. The Access Testosterone method could be considered an adequately reliable tool for the testosterone measurement. © 2017 Wiley Periodicals, Inc.

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

PubMed

Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

2001-09-01

To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

Anabolic and Catabolic Biomarkers As Predictors of Muscle Strength Decline: The InCHIANTI Study

PubMed Central

Maggio, Marcello; Lauretani, Fulvio; Bandinelli, Stefania; Ceda, Gian Paolo; Di Iorio, Angelo; Giallauria, Francesco; Guralnik, Jack M.; Ferrucci, Luigi

2010-01-01

Abstract Background Poor muscle strength is a major public health concern in older persons, predisposing to functional limitations, increased fall risk, and higher mortality. Understanding risk factors for muscle strength decline may offer opportunities for prevention and treatment. One of the possible causes of muscle strength decline is imbalance between catabolic and anabolic signaling. This study aims to examine whether high levels of multiple catabolic and low levels of multiple anabolic biomarkers predict accelerated decline of muscle strength. Methods In a representative sample of 716 men and women aged ≥65 years in the InCHIANTI study we measured C-reactive protein, interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-α receptor 1 as well as dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1, and bioavailable testosterone. Biomarker values were divided into tertiles and the numbers of catabolic/anabolic biomarkers in the highest/lowest tertile were calculated. Hand-grip strength was measured at baseline and 3- and 6-year follow up. Results In adjusted linear mixed models, higher concentration of IL-6 (p = 0.02) and IL-1RA (p = 0.04) as well as lower levels of DHEA-S (p = 0.01) predicted muscle strength decline. After combining all inflammatory markers, the rate of decline in grip strength was progressively greater with the increasing number of dysregulated catabolic biomarkers (p = 0.01). No effect on accelerated muscle strength decline was seen according to number of dysregulated anabolic hormones. Conclusions Having multiple elevated catabolic biomarkers is a better predictor of muscle strength decline than a single biomarker alone, suggesting that a catabolic dysregulation is at the core of the mechanism leading to muscle strength decline with aging. PMID:20230273

Premature adrenarche: etiology, clinical findings, and consequences.

PubMed

Voutilainen, Raimo; Jääskeläinen, Jarmo

2015-01-01

Adrenarche means the morphological and functional change of the adrenal cortex leading to increasing production of adrenal androgen precursors (AAPs) in mid childhood, typically at around 5-8 years of age in humans. The AAPs dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the best serum markers of adrenal androgen (AA) secretion and adrenarche. Normal ACTH secretion and action are needed for adrenarche, but additional inherent and exogenous factors regulate AA secretion. Inter-individual variation in the timing of adrenarche and serum concentrations of DHEA(S) in adolescence and adulthood are remarkable. Premature adrenarche (PA) is defined as the appearance of clinical signs of androgen action (pubic/axillary hair, adult type body odor, oily skin or hair, comedones, acne, accelerated statural growth) before the age of 8 years in girls or 9 years in boys associated with AAP concentrations high for the prepubertal chronological age. To accept the diagnosis of PA, central puberty, adrenocortical and gonadal sex hormone secreting tumors, congenital adrenal hyperplasia, and exogenous source of androgens need to be excluded. The individually variable peripheral conversion of circulating AAPs to biologically more active androgens (testosterone, dihydrotestosterone) and the androgen receptor activity in the target tissues are as important as the circulating AAP concentrations as determinants of androgen action. PA has gained much attention during the last decades, as it has been associated with small birth size, the metabolic and polycystic ovarian syndrome (PCOS), and thus with an increased risk for type 2 diabetes and cardiovascular diseases in later life. The aim of this review is to describe the known hormonal changes and their possible regulators in on-time and premature adrenarche, and the clinical features and possible later health problems associating with PA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adrenocortical Hormone Abnormalities in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Dimitrakov, Jordan; Joffe, Hylton V.; Soldin, Steven J.; Bolus, Roger; Buffington, C.A. Tony; Nickel, J Curtis

2007-01-01

Objectives To identify adrenocortical hormone abnormalities as indicators of endocrine dysfunction in CP/CPPS. Methods We simultaneously measured the serum concentrations of 12 steroids in CP/CPPS and control patients, using isotope dilution liquid chromatography followed by atmospheric pressure photospray ionization and tandem mass spectrometry. Results Twenty-seven CP/CPPS patients and 29 age-matched asymptomatic healthy controls were evaluated. In the mineralocorticoid pathway, progesterone was significantly higher, whereas corticosterone and aldosterone concentrations were significantly lower, in CP/CPPS than in controls. In the glucocorticoid pathway, 11-deoxycortisol was significantly lower, and cortisol concentrations were not different between patients and controls. In the sex steroid pathway, androstenedione and testosterone concentrations were significantly higher in CP/CPPS than in controls. Estradiol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrations were not different between patients and controls. NIH-CPSI total and pain domain scores correlated positively with 17-hydroxyprogesterone and aldosterone (P<0.001) and negatively with cortisol concentrations (P<0.001). Conclusions Results suggest reduced activity of CYP21A2 (P450c21), the enzyme that converts progesterone to corticosterone, and 17-hydroxyprogesterone to 11-deoxycortisol. Furthermore, these results provide insights into the biological basis of CP/CPPS. Follow-up studies should explore the possibility that CP/CPPS patients meet the diagnostic criteria for nonclassical CAH and if hormonal findings improve or worsen in parallel with symptom severity. PMID:18308097

Prostate cancer risk: the significance of differences in age related changes in serum conjugated and unconjugated steroid hormone concentrations between Arab and Caucasian men.

PubMed

Kehinde, E O; Akanji, A O; Memon, A; Bashir, A A; Daar, A S; Al-Awadi, K A; Fatinikun, T

2006-01-01

Factors responsible for the low incidence of clinical prostate cancer (3-8/100,000 men/year) in the Arab population remain unclear, but may be related to changes in steroid hormone metabolism. We compared the levels of serum conjugated and unconjugated steroids between Arab and Caucasian populations, to determine if these can provide a rational explanation for differences in incidence of prostate cancer between the two populations. Venous blood samples were obtained from 329 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-80 years. Samples were also obtained from similar Arab men with newly diagnosed prostate cancer or benign prostatic hyperplasia (BPH). The samples were taken between 8:00 am and 12:00 noon. Serum levels of total testosterone, (TT), sex hormone binding globulin (SHBG), free androgen index (FAI); adrenal C19-steroids, dehydroepiandrosterone sulphate (DHEAS) and androstenedione (ADT) were determined using Immulite kits (Diagnostic Systems Laboratories Inc, Webster Texas, USA). The results obtained in Arab men were compared with those reported for similarly aged Chinese, German and White USA men. In all four ethnic groups, median TT and FAI declined with age, while SHBG increased with age. However, the mean TT and SHBG was significantly lower (p < 0.01) and the FAI significantly higher in Arab men (p < 0.01) compared to German men only in 21-30 years age group. In the other age groups the levels of TT and SHBG were higher in the Germans but the differences were not statistically significant. In all the racial groups serum levels of DHEAS and ADT reached a peak by about 20 years of life, and then declined progressively. The mean DHEAS in American Caucasians aged 20-29 years was 11.4 micromol/l compared to 6.22 micromol/l in the Arabs (p < 0.001). The mean DHEAS in USA Caucasians aged 70-79 years was 2.5 micromol/l compared to 1.8 micromol/l (p < 0.03) in the Arabs. There was no significant difference in mean serum levels

Depression, Anxiety, and Anger in Patients with Polycystic Ovary Syndrome

PubMed Central

BALIKCI, Adem; ERDEM, Murat; KESKIN, Uğur; BOZKURT ZINCIR, Selma; GÜLSÜN, Murat; ÖZÇELIK, Fatih; AKGÜL, Emin Özgür; AKARSU, Süleyman; ÖZTOSUN, Muzaffer; ERGÜN, Ali

2014-01-01

Introduction Polycystic Ovary Syndrome (PCOS) is a syndrome of heterogeneous nature, affecting multiple systems, particularly the endocrine system. We propose to investigate the possible relationships among hormonal changes, levels of anxiety, depression, and anger in patients with PCOS. Method Forty-four female patients with PCOS and 44 body mass index (BMI )-matched healthy women participated in this study. We measured the sociodemographic features, some serum hormonal levels (insulin, gonadotropins, prolactin, dehydroepiandrosterone sulfate (DHEAS), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), 17 OH-progesterone, and total and free testosterone), and some other biochemical parameters of the participants. Also, all participants completed the Trait Anger-Anger Expression Scale (STAS), Beck Depression, and Beck Anxiety Inventories. We evaluated the psychiatric scale scores obtained from PCOS patients and control subjects. We used the independent-samples t-test for parametric data to evaluate normal distribution, and Mann-Whitney U-test was used for both abnormally distributed and nonparametric data. We used Pearson correlation analysis to evaluate the potential connection between the two groups’ data. Results The mean ages of the patients with PCOS and control subjects who participated in this study were 27.3±5.6 and 27.4±6.1 years, respectively. The measures of BMI, insulin, luteinizing hormone (LH), DHEAS, and total testosterone serum levels in the patient group were significantly higher than in the control group (p<.05). There was a statistically significant positive correlation between Beck anxiety scores and serum DHEAS levels (Pearson r=.4366, P=.0001). We found significant differences between the two groups in terms of trait anger, anger control, outward and inward anger, anxiety level, and depression scores (P<.05). Conclusion Anxiety symptoms indicate a stronger relationship compared to depression with DHEAS serum levels

Effect of leuprolide and dexamethasone on hair growth and hormone levels in hirsute women: the relative importance of the ovary and the adrenal in the pathogenesis of hirsutism.

PubMed

Rittmaster, R S; Thompson, D L

1990-04-01

Ten hirsute women with polycystic ovarian syndrome (PCO) and nine with idiopathic hirsutism (IH) underwent selective ovarian suppression with leuprolide for 5-6 months and then were randomized to receive, in addition, dexamethasone or placebo for 4 more months. Serum hormone levels and hair growth rates were determined before and after each treatment period. During the initial treatment period with leuprolide alone, testosterone decreased by 54 +/- 6% (mean +/- SEM) in PCO and by 36 +/- 3% in IH (P = 0.02). Androstenedione decreased by 53 +/- 6% in PCO and by 31 +/- 7% in IH (P = 0.02). Androstanediol glucuronide (Adiol-G) decreased by 14 +/- 6% in PCO and by 7 +/- 3% in IH. There was no change in dehydroepiandrosterone sulfate (DHEAS). While initial serum androgen levels were higher in PCO than in IH, they were similar after ovarian suppression in the two groups. After ovarian suppression, Adiol-G was more consistently correlated with testosterone and androstenedione than was DHEAS, suggesting that Adiol-G may be a better marker than DHEAS of adrenal androgen secretion. Hair growth rates decreased by 37 +/- 6% in PCO and by 14 +/- 10% in IH (P = 0.07). The change in hair growth correlated with the change in androstenedione (r = 0.66; P = 0.002), but not significantly with the change in testosterone (r = 0.29; P = 0.2). After the addition of dexamethasone therapy (0.5 mg daily), testosterone, androstenedione, and DHEAS levels fell to near or below assay detection limits, while Adiol-G decreased by 80 +/- 3%. Hair growth rates decreased slightly more in women during dexamethasone (46 +/- 6%) than during placebo (26 +/- 9%; P = 0.18). In summary, the ovary was the major source of circulating testosterone and androstenedione in PCO. The adrenal contributed a substantial minority of these hormones in PCO and was the major source of androgen secretion in IH. Adrenal hyperandrogenism was common in both IH and PCO. Hair growth rates correlated best with changes in serum

Impaired receptivity and decidualization in DHEA-induced PCOS mice.

PubMed

Li, Shu-Yun; Song, Zhuo; Song, Min-Jie; Qin, Jia-Wen; Zhao, Meng-Long; Yang, Zeng-Ming

2016-12-07

Polycystic ovary syndrome (PCOS), a complex endocrine disorder, is a leading cause of female infertility. An obvious reason for infertility in PCOS women is anovulation. However, success rate with high quality embryos selected by assisted reproduction techniques in PCOS patients still remain low with a high rate of early clinical pregnancy loss, suggesting a problem in uterine receptivity. Using a dehydroepiandrosterone-induced mouse model of PCOS, some potential causes of decreased fertility in PCOS patients were explored. In our study, ovulation problem also causes sterility in PCOS mice. After blastocysts from normal mice are transferred into uterine lumen of pseudopregnant PCOS mice, the rate of embryo implantation was reduced. In PCOS mouse uteri, the implantation-related genes are also dysregulated. Additionally, artificial decidualization is severely impaired in PCOS mice. The serum estrogen level is significantly higher in PCOS mice than vehicle control. The high level of estrogen and potentially impaired LIF-STAT3 pathway may lead to embryo implantation failure in PCOS mice. Although there are many studies about effects of PCOS on endometrium, both embryo transfer and artificial decidualization are applied to exclude the effects from ovulation and embryos in our study.

Impaired receptivity and decidualization in DHEA-induced PCOS mice

PubMed Central

Li, Shu-Yun; Song, Zhuo; Song, Min-Jie; Qin, Jia-Wen; Zhao, Meng-Long; Yang, Zeng-Ming

2016-01-01

Polycystic ovary syndrome (PCOS), a complex endocrine disorder, is a leading cause of female infertility. An obvious reason for infertility in PCOS women is anovulation. However, success rate with high quality embryos selected by assisted reproduction techniques in PCOS patients still remain low with a high rate of early clinical pregnancy loss, suggesting a problem in uterine receptivity. Using a dehydroepiandrosterone-induced mouse model of PCOS, some potential causes of decreased fertility in PCOS patients were explored. In our study, ovulation problem also causes sterility in PCOS mice. After blastocysts from normal mice are transferred into uterine lumen of pseudopregnant PCOS mice, the rate of embryo implantation was reduced. In PCOS mouse uteri, the implantation-related genes are also dysregulated. Additionally, artificial decidualization is severely impaired in PCOS mice. The serum estrogen level is significantly higher in PCOS mice than vehicle control. The high level of estrogen and potentially impaired LIF-STAT3 pathway may lead to embryo implantation failure in PCOS mice. Although there are many studies about effects of PCOS on endometrium, both embryo transfer and artificial decidualization are applied to exclude the effects from ovulation and embryos in our study. PMID:27924832

Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers

PubMed Central

2014-01-01

Background L-ornithine is a non-essential, non-protein amino acid. Although L-ornithine is contained in various foods, the amount is usually small. Recently, studies have shown that orally administered L-ornithine reduced the stress response in animals. From these findings, we speculated that L-ornithine may play a role in the relieve of stress and improve sleep and fatigue symptoms in humans. Through a randomised, double-blind, placebo-controlled clinical study, we asked if L-ornithine could be beneficial to stress and sleep in healthy workers. Method Fifty-two apparently healthy Japanese adults who had previously felt slight stress as well as fatigue were recruited to be study participants and were randomly divided into either the L-ornithine (400 mg/day) or placebo group. They orally consumed the respective test substance every day for 8 weeks. Serum was collected for the assessment of cortisol and dehydroepiandrosterone-sulphate (DHEA-S). Perceived mood and quality of sleep were measured by the Profile of Mood States (POMS), Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). Results Serum cortisol levels and the cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group in comparison with the placebo group. Also, anger was reduced and perceived sleep quality was improved in the L-ornithine group. Conclusion L-ornithine supplementation has the potential to relieve stress and improve sleep quality related to fatigue, both objectively and subjectively. PMID:24889392

Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers.

PubMed

Miyake, Mika; Kirisako, Takayoshi; Kokubo, Takeshi; Miura, Yutaka; Morishita, Koji; Okamura, Hisayoshi; Tsuda, Akira

2014-06-03

L-ornithine is a non-essential, non-protein amino acid. Although L-ornithine is contained in various foods, the amount is usually small.Recently, studies have shown that orally administered L-ornithine reduced the stress response in animals.From these findings, we speculated that L-ornithine may play a role in the relieve of stress and improve sleep and fatigue symptoms in humans. Through a randomised, double-blind, placebo-controlled clinical study, we asked if L-ornithine could be beneficial to stress and sleep in healthy workers. Fifty-two apparently healthy Japanese adults who had previously felt slight stress as well as fatigue were recruited to be study participants and were randomly divided into either the L-ornithine (400 mg/day) or placebo group. They orally consumed the respective test substance every day for 8 weeks. Serum was collected for the assessment of cortisol and dehydroepiandrosterone-sulphate (DHEA-S). Perceived mood and quality of sleep were measured by the Profile of Mood States (POMS), Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). Serum cortisol levels and the cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group in comparison with the placebo group. Also, anger was reduced and perceived sleep quality was improved in the L-ornithine group. L-ornithine supplementation has the potential to relieve stress and improve sleep quality related to fatigue, both objectively and subjectively.

Night shift work and other determinants of estradiol, testosterone, and dehydroepiandrosterone sulfate among middle-aged nurses and midwives.

PubMed

Peplonska, Beata; Bukowska, Agnieszka; Lie, Jenny Anne; Gromadzinska, Jolanta; Zienolddiny, Shanbeh

2016-09-01

The aims of our study were to (i) investigate the association between rotating night shift work and blood concentrations of estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) and (2) evaluate the role of their non-occupational determinants. A cross-sectional study was conducted on 345 premenopausal and 187 postmenopausal nurses and midwives (263 women working rotating night shifts and 269 women working during days). Data from in-person interviews were used, anthropometric measurements were performed, and body mass index (BMI) and waist- to-hip ratio were calculated. Morning blood and spot urine samples were collected. Multiple linear regression models were fitted with hormone concentrations as dependent variables, and night shift work characteristics and demographic, reproductive, lifestyle and anthropometric determinants as independent variables. Modification of the effect by chronotype was examined. Among postmenopausal women, we observed a statistically significant positive association between the total duration of night shift work >15 years and estradiol level (P<0.05 when compared to night work duration <5 years). Night shift work characteristics were significantly associated with estradiol among morning-type postmenopausal women. The well-established associations between hormones and their major determinants, such as age and BMI, were confirmed. The findings of our study imply that prolonged night shift work may be associated with increased estradiol levels among postmenopausal women, especially among the morning-type postmenopausal women.

Clinical Assessment of Tribulus terrestris Extract in the Treatment of Female Sexual Dysfunction

PubMed Central

Gama, Carlos RB; Lasmar, Ricardo; Gama, Gustavo F; Abreu, Camila S; Nunes, Carlos P; Geller, Mauro; Oliveira, Lisa; Santos, Alessandra

2014-01-01

This is a qualitative–quantitative study based on hospital records of female patients of reproductive age, presenting sexual dysfunction, and treated with 250 mg Tribulus terrestris extract (1 tablet thrice daily for 90 days). Safety monitoring included vital signs, physical examination, laboratory tests, and occurrence of adverse events. Efficacy analysis included results of the Female Sexual Function Index (FSFI), dehydroepiandrosterone (DHEA) levels together with total and free testosterone, and the patient and physician assessments. There was a statistically significant improvement in total FSFI scores (P < 0.0001) post-treatment, with improvement among 106 (88.33%) subjects. There was a statistically significant (P < 0.0001) increase in the level of DHEA, while the levels of both serum testosterone (P = 0.284) and free testosterone decreased (P < 0.0001). Most adverse events recorded were related to the gastrointestinal tract. Physical examination showed no significant changes post-treatment. Based on the results, it is concluded that the T. terrestris extract is safe and effective in the treatment of female sexual dysfunction. PMID:25574150

Clinical Assessment of Tribulus terrestris Extract in the Treatment of Female Sexual Dysfunction.

PubMed

Gama, Carlos Rb; Lasmar, Ricardo; Gama, Gustavo F; Abreu, Camila S; Nunes, Carlos P; Geller, Mauro; Oliveira, Lisa; Santos, Alessandra

2014-01-01

This is a qualitative-quantitative study based on hospital records of female patients of reproductive age, presenting sexual dysfunction, and treated with 250 mg Tribulus terrestris extract (1 tablet thrice daily for 90 days). Safety monitoring included vital signs, physical examination, laboratory tests, and occurrence of adverse events. Efficacy analysis included results of the Female Sexual Function Index (FSFI), dehydroepiandrosterone (DHEA) levels together with total and free testosterone, and the patient and physician assessments. There was a statistically significant improvement in total FSFI scores (P < 0.0001) post-treatment, with improvement among 106 (88.33%) subjects. There was a statistically significant (P < 0.0001) increase in the level of DHEA, while the levels of both serum testosterone (P = 0.284) and free testosterone decreased (P < 0.0001). Most adverse events recorded were related to the gastrointestinal tract. Physical examination showed no significant changes post-treatment. Based on the results, it is concluded that the T. terrestris extract is safe and effective in the treatment of female sexual dysfunction.

Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

PubMed Central

Yuan, Xiaoxue; Hu, Tao; Zhao, Han; Huang, Yuanyuan; Ye, Rongcai; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Zhou, Huiqiao; Dong, Meng; Zhao, Jun; Wang, Haibin; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu; Chen, Zi-Jiang

2016-01-01

Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS. PMID:26903641

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

PubMed

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

2017-12-01

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

Do differences in age specific androgenic steroid hormone levels account for differing prostate cancer rates between Arabs and Caucasians?

PubMed

Kehinde, Elijah O; Akanji, Abayomi O; Al-Hunayan, Adel; Memon, Anjum; Luqmani, Yunus; Al-Awadi, Khaleel A; Varghese, Ramani; Bashir, Abdul Aziz; Daar, Abdallah S

2006-04-01

Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with

Increased symptoms of anxiety and depression in prepubertal girls, but not boys, with premature adrenarche: associations with serum DHEAS and daily salivary cortisol concentrations.

PubMed

Marakaki, Chrisanthi; Pervanidou, Panagiota; Papassotiriou, Ioannis; Mastorakos, George; Hochberg, Ze'ev; Chrousos, George; Papadimitriou, Anastasios

2018-06-19

Concerns over anxiety and depressive symptoms in children with premature adrenarche (PA) have been recently raised. However, to date, most relevant studies are on a small number of girls. In this cross-sectional study, 82 pre-pubertal children (66 girls and 16 boys) diagnosed with PA, were compared to 63 control children regarding their psychological characteristics and hypothalamic-pituitary-adrenal (HPA) axis function, as assessed by salivary cortisol measurement. Symptoms of anxiety and depression were assessed by child self-report (Spence Children's Anxiety Scale (SCAS) and Depression self-rating scale for Children (DSRS)) and parent-report (Child Behaviour Checklist (CBCL)) tests validated for the Greek population. Salivary cortisol levels were determined directly after awakening (approximately 7am) and evening (8pm) of the same day. Morning serum DHEAS levels were assessed in PA children. Girls with PA scored significantly higher on anxiety (p = .016) and depression (p =.039) scales than controls. No group differences were noted for parent reports and children's salivary cortisol concentrations. Boys with PA did not demonstrate significant differences in any of the aforementioned parameters. Our findings suggest that girls with PA may be at higher risk for reporting symptoms of anxiety and depression than their non-PA peers. HPA axis dysregulation in this population was not documented.

Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers.

PubMed

Pandit, S; Biswas, S; Jana, U; De, R K; Mukhopadhyay, S C; Biswas, T K

2016-06-01

Purified Shilajit, an Ayurvedic rasayana, was evaluated in healthy volunteers of age between 45 and 55 years for its effect on male androgenic hormone viz. testosterone in a randomised, double-blind, placebo-controlled clinical study at a dose of 250 mg twice a day. Treatment with Shilajit for consecutive 90 days revealed that it has significantly (P < 0.05) increased total testosterone, free testosterone and dehydroepiandrosterone (DHEAS) compared with placebo. Gonadotropic hormones (LH and FSH) levels were well maintained. © 2015 The Authors. Andrologia Published by Blackwell Verlag GmbH.

Parity modifies endocrine hormones in urine and problem-solving strategies of captive owl monkeys (Aotus spp.).

PubMed

Bardi, Massimo; Eckles, Meredith; Kirk, Emily; Landis, Timothy; Evans, Sian; Lambert, Kelly G

2014-12-01

Parental behavior modifies neural, physiologic, and behavioral characteristics of both maternal and paternal mammals. These parenting-induced modifications extend to brain regions not typically associated with parental responses themselves but that enhance ancillary responses, such as foraging efficiency and predator avoidance. Here we hypothesized that male and female owl monkeys (Aotus spp.) with reproductive experience (RE) would demonstrate more adaptive ancillary behavioral and neuroendocrine responses than those of their nonRE counterparts. To assess cognitive skills and coping flexibility, we introduced a foraging strategy task, including a set of novel objects (coin holders) marked with different symbols representing different food rewards, to the animals. To assess endocrine responses, urine samples were assayed for cortisol and dehydroepiandrosterone (DHEA) levels and their ratios to determine physiologic measures of emotional regulation in RE and nonRE owl monkeys. Compared with nonRE monkeys, experienced parents had higher DHEA:cortisol ratios after exposure to habituation training and on the first day of testing in the foraging task. Both hormones play critical roles in the stress response and coping mechanisms, and a high DHEA:cortisol ratio usually indicates increased coping skills. In addition, RE monkeys exhibited more efficient foraging responses (by 4-fold) than did the nonRE mating pairs. We conclude that RE modifies relevant behavioral and hormonal responses of both maternal and paternal owl monkeys exposed to a challenging cognitive paradigm. Corroborating previous research demonstrating adaptive modifications in foraging efficiency and emotional responses in reproductively experienced rodents, the current results extend these findings to a monogamous primate species.

Primary hepatocytes as an useful bioassay to characterize metabolism and bioactivity of illicit steroids in cattle.

PubMed

Giantin, Mery; Gallina, Guglielmo; Pegolo, Sara; Lopparelli, Rosa Maria; Sandron, Clara; Zancanella, Vanessa; Nebbia, Carlo; Favretto, Donata; Capolongo, Francesca; Montesissa, Clara; Dacasto, Mauro

2012-10-01

Cattle hepatocytes have already been used in veterinary in vitro toxicology, but their usefulness as a multi-parametric screening bioassay has never been investigated so far. In this study, cattle hepatocytes were incubated with illicit steroids/prohormones (boldenone, BOLD; its precursor boldione, ADD; dehydroepiandrosterone, DHEA; an association of ADD:BOLD), to characterize their transcriptional effects on drug metabolizing enzymes (DMEs) and related nuclear receptors (NRs), on cytochrome P450 3A (CYP3A) apoprotein and catalytic activity as well as to determine ADD and BOLD metabolite profiling. DHEA-exposed cells showed an up-regulation (higher than 2.5-fold changes) of three out of six NRs, CYP2B22 and CYP2C87; likewise, ADD:BOLD increased CYP4A11 mRNA levels. In contrast, a reduction of CYP1A1 and CYP2E1 mRNAs (lower than 2.5(-1)-fold changes) was noticed in ADD- and DHEA-incubated cells. No effect was noticed on CYP3A gene and protein expression, though an inhibition of 6β-, 2β- and 16β-hydroxylation of testosterone (higher than 60% of control cells) was observed in ADD- and BOLD-exposed cells. Finally, 17α-BOLD was the main metabolite extracted from hepatocyte media incubated with ADD and BOLD, but several mono-hydroxylated BOLD and ADD derivatives were detected, too. Collectively, cattle hepatocytes can represent a complementary screening bioassay, useful to characterize growth promoters metabolite profiling and their effects upon DMEs expression, regulation and function. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

PubMed

Wachs, Deborah S; Coffler, Mickey S; Malcom, Pamela J; Shimasaki, Shunichi; Chang, R Jeffrey

2008-05-01

In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. A prospective study was conducted to compare androgen production in response to FSH in two groups of women. The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome.

PubMed

Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Abbott, David H

2005-12-01

Adrenal androgen excess is found in approximately 25-60% of women with polycystic ovary syndrome (PCOS), but the mechanisms underlying PCOS-related adrenal androgen excess are unclear. The objective of this study was to determine whether adrenal androgen excess is manifest in a nonhuman primate model for PCOS. Six prenatally androgenized (PA) and six control female rhesus monkeys of similar age, body weight, and body mass index were studied during d 2-6 of two menstrual cycles or anovulatory 30-d periods. Predexamethasone adrenal steroid levels were assessed in the first cycle (cycle 1). In a subsequent cycle (cycle 2), occurring one to three cycles after cycle 1, adrenal steroids were determined 14.5-16.0 h after an i.m. injection of 0.5 mg/kg dexamethasone (postdexamethasone levels) and after an i.v. injection of 50 microg ACTH-(1-39). Both before and after dexamethasone, serum levels of dehydroepiandrosterone (DHEA) in PA females exceeded those in controls. After ACTH injection, PA females exhibited higher circulating levels of DHEA, androstenedione, and corticosterone but comparable levels of 17alpha-hydroxyprogesterone, cortisol, the sulfoconjugate of DHEA, and testosterone compared with controls. Enhanced basal and ACTH-stimulated adrenal androgen levels in PA female monkeys may reflect up-regulation of 17,20 lyase activity in the adrenal zona reticularis, causing adrenal androgen excess comparable with that found in PCOS women with adrenal androgen excess. These findings open the possibility that PCOS adrenal hyperandrogenism may have its origins in fetal androgen excess reprogramming of adrenocortical function.

Parity Modifies Endocrine Hormones in Urine and Problem-Solving Strategies of Captive Owl Monkeys (Aotus spp.)

PubMed Central

Eckles, Meredith; Kirk, Emily; Landis, Timothy; Evans, Sian; Lambert, Kelly G

2014-01-01

Parental behavior modifies neural, physiologic, and behavioral characteristics of both maternal and paternal mammals. These parenting-induced modifications extend to brain regions not typically associated with parental responses themselves but that enhance ancillary responses, such as foraging efficiency and predator avoidance. Here we hypothesized that male and female owl monkeys (Aotus spp.) with reproductive experience (RE) would demonstrate more adaptive ancillary behavioral and neuroendocrine responses than those of their nonRE counterparts. To assess cognitive skills and coping flexibility, we introduced a foraging strategy task, including a set of novel objects (coin holders) marked with different symbols representing different food rewards, to the animals. To assess endocrine responses, urine samples were assayed for cortisol and dehydroepiandrosterone (DHEA) levels and their ratios to determine physiologic measures of emotional regulation in RE and nonRE owl monkeys. Compared with nonRE monkeys, experienced parents had higher DHEA:cortisol ratios after exposure to habituation training and on the first day of testing in the foraging task. Both hormones play critical roles in the stress response and coping mechanisms, and a high DHEA:cortisol ratio usually indicates increased coping skills. In addition, RE monkeys exhibited more efficient foraging responses (by 4-fold) than did the nonRE mating pairs. We conclude that RE modifies relevant behavioral and hormonal responses of both maternal and paternal owl monkeys exposed to a challenging cognitive paradigm. Corroborating previous research demonstrating adaptive modifications in foraging efficiency and emotional responses in reproductively experienced rodents, the current results extend these findings to a monogamous primate species. PMID:25527030

Dual targeting of the antagonistic pathways mediated by Sirt1 and TXNIP as a putative approach to enhance the efficacy of anti-aging interventions

PubMed Central

Mousa, Shaker A.; Gallati, Christine; Simone, Tessa; Dier, Emmy; Yalcin, Murat; Dyskin, Evgeny; Thangirala, Sudha; Hanko, Christine; Rebbaa, Abdelhadi

2009-01-01

The organism's ability to regulate oxidative stress and metabolism is well recognized as a major determinant of longevity. While much research interest in this area is directed towards the study of genes that inhibit oxidative stress and/or improve metabolism, contribution to the aging process of genes with antagonistic effects on these two pathways is still less understood. The present study investigated the respective roles of the histone deacetylase Sirt1 and the thioredoxin binding protein TXNIP, two genes with opposite effects on oxidative stress and metabolism, in mediating the action of putative anti-aging interventions. Experiments were carried out in vitro and in vivo to determine the effect of proven, limited calorie availability, and unproven, resveratrol and dehydroepiandrosterone (DHEA), on the expression of Sirt1 and TXNIP. The results indicated that limited calorie availability consistently inhibited TXNIP in cancer and in normal cells including stem cells, however, it only slightly induced Sirt1expression in cancer cells. In contrast, resveratrol had a biphasic effect, and DHEA inhibited the expression of these two genes in a tissue specific manner, both in vitro and in vivo. Whereas all the three approaches tested inhibited TXNIP through the glycolytic pathway, DHEA acted by inhibiting G6PD and resveratrol through the activation of AMPK. In light of previous reports that Sirt1 induces AMPK-mediated signaling pathway, our findings point to the possibility of a negative relationship between Sirt1 and TXNIP that, if validated, can be exploited to improve the efficacy of putative anti-aging interventions. PMID:20195491

The Impact of Chocolate Goat's and Cow's Milk on Postresistance Exercise Endocrine Responses and Isometric Mid-Thigh Pull Performance.

PubMed

Bellar, David; LeBlanc, Nina R; Murphy, Kellie; Moody, Kaitlyn M; Buquet, Gina

2016-01-01

The present investigation examined the effects of chocolate cow's and goat's milk on endocrine responses and isometric mid-thigh pull performance post back squat exercise. Twelve college-aged males volunteered to participate and reported to the lab on four occasions. The first visit included anthropometric measurement, one-repetition back squat (1RM), and familiarization with the isometric mid-thigh pull assessment (IMTP). During the subsequent three visits, five sets of eight repetitions of the back squat exercise at 80% of 1RM were performed. For these trials, the participants performed an IMTP and gave a saliva sample prior to, immediately after, 1 hr and 2 hr post exercise. After exercise, a treatment of low-fat chocolate goat's milk (355 ml, 225 kcal), low-fat chocolate cow's milk (355 ml, 225 kcal), or control (water 355 ml, 0 kcal) was given in a counterbalanced order. Saliva samples were analyzed for testosterone, cortisol, and dehydroepiandrosterone (DHEA). Cortisol and DHEA hormone were unaffected by exercise; however, testosterone values did increase significantly post exercise. For IMTP, there was a significant main effect for time (F = 8.41, p = .007) but no treatment or interactions effects. N changes were noted post supplementation for cortisol or DHEA, but testosterone was found to be significantly reduced in both diary treatments compared to control (F = 4.27, p = .022). Based upon these data, it appears that a single treatment of chocolate goat's or cow's milk results in similar endocrine alterations but both fail to enhance postexercise isometric strength following resistance exercise.

Association between hormones and metabolic syndrome in older Italian men.

PubMed

Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo; Bandinelli, Stefania; Basaria, Shehzad; Ble, Alessandro; Egan, Josephine; Paolisso, Giuseppe; Najjar, Samer; Jeffrey Metter, E; Valenti, Giorgio; Guralnik, Jack M; Ferrucci, Luigi

2006-12-01

To determine whether low levels of testosterone, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and dehydroepiandrosterone sulfate (DHEAS) and high levels of cortisol and leptin would be associated with metabolic syndrome (MS). Cross-sectional. Population-based sample of older Italian men. Four hundred fifty-two men aged 65 and older enrolled in the Invecchiare in Chianti (InCHIANTI) study. Complete data on testosterone, cortisol, DHEAS, SHBG, fasting insulin, IGF-1 and leptin. MS was defined according to Adult Treatment Panel III criteria. MS was present in 73 men (15.8% of the sample). After adjusting for confounders, total testosterone (P < .05) and log (SHBG) (P < .001) were inversely associated, whereas log (leptin) was positively associated with MS (P < .001). Independent of age, log (SHBG) was positively associated with high-density lipoprotein cholesterol (P < .05) and negatively associated with abdominal obesity (P < .001) and triglycerides (P < .001). Log (leptin) was significantly associated with each component of MS. Cortisol, DHEAS, free and bioavailable testosterone, and IGF-1 were not associated with MS. Having three or more hormones in the lower (for hormones lower in MS) or the upper (for hormones higher in MS) quartile was associated with three times the risk of being affected by MS (odds ratio = 2.8, 95% confidence interval = 1.3-6.9) (P = .005), compared with not having this condition. Total testosterone and SHBG are negatively and leptin is positively associated with MS in older men. Whether specific patterns of hormonal dysregulation predict the development of MS should be tested in longitudinal studies.

Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: a nested case-referent study.

PubMed

Holl, Katsiaryna; Lundin, Eva; Surcel, Heljä-Marja; Grankvist, Kjell; Koskela, Pentti; Dillner, Joakim; Hallmans, Göran; Wadell, Göran; Olafsdottir, Gudridur H; Ogmundsdottir, Helga M; Pukkala, Eero; Lehtinen, Matti; Stattin, Pär; Lukanova, Annekatrin

2009-06-15

According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. Copyright 2008 UICC.

Comparative Analysis of Psychological, Hormonal, and Genetic Factors Between Burning Mouth Syndrome and Secondary Oral Burning.

PubMed

das Neves de Araújo Lima, Emeline; Barbosa, Natália Guimarães; Dos Santos, Ana Celly Souza; AraújoMouraLemos, Telma Maria; de Souza, Cleber Machado; Trevilatto, Paula Cristina; da Silveira, Ericka Janine Dantas; de Medeiros, Ana Miryam Costa

2016-09-01

The objective of this study was to evaluate the association between psychological, hormonal, and genetic factors with the development of burning mouth syndrome (BMS) and secondary oral burning (SOB) in order to provide a better characterization and classification of these conditions. Cross sectional study. Patients with complaints of mouth burning registered at the Oral Diagnostic Service of the Federal University of Rio Grande do Norte between 2000 and 2013. The sample consisted of 163 subjects divided into a group of patients with BMS (n = 64) and a group of subjects with SOB (n = 99). The following variables were analyzed: passive and stimulated saliva flow, stress levels and phase, depression, anxiety, serum cortisol and dehydroepiandrosterone (DHEA) levels, and the presence of polymorphisms in the interleukin 6 (IL-6) gene. The results showed significant differences in the presence of xerostomia (p = 0.01), hyposalivation at rest (p < 0.001) and symptoms of depression (p = 0.033) between the two groups, which were more prevalent in the BMS group. DHEA levels were lower in the BMS group (p = 0.003) and were sensitive and specific for the diagnosis of this condition. Genetic analysis revealed no significant association between the polymorphisms analyzed and the development of BMS. These results suggest a possible role of depression, as well as of reduced DHEA levels, as associated factors for development of BMS. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The effect and mechanism of inhibiting glucose-6-phosphate dehydrogenase activity on the proliferation of Plasmodium falciparum.

PubMed

Zhang, Zhiqiang; Chen, Xiaodan; Jiang, Chengrui; Fang, Zishui; Feng, Yi; Jiang, Weiying

2017-05-01

We screened >40,000 patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and found that the G6PD Kaiping allele was under the most positive selection for fighting against malaria in the Chinese population. However, the mechanism is unknown. The current study was designed to investigate the anti-malarial effect and mechanism of G6PD deficiency. Dehydroepiandrosterone (DHEA) was utilised for inhibiting the G6PD activity of erythrocytes. Giemsa staining of blood smears and quantitative real-time PCR were used for the detection and quantification of Plasmodium falciparum infection. A transmission electron microscope was used to observe the structural changes of P. falciparum. An atomic force microscopy was used for the analyses of morphology, roughness and Young's Modulus of the infective erythrocyte membrane. When G6PD activity was inhibited by DHEA, the infection rate of P. falciparum decreased, its cell nucleus shrank, the cell organelles and metabolites were reduced gradually and the Young's Modulus of the erythrocyte membrane increased with increasing DHEA concentrations. These data indicated that Plasmodium multiplication would be inhibited in G6PD deficient erythrocytes because the Plasmodium organelles could not obtain enough nutrients, including ribose-5-phosphate and the reducing equivalent, NADPH. Moreover, the Young's Modulus of the erythrocyte membrane increased, which resulted in an increased membrane stiffness and decreased deformation. It was difficult for the merozoites to invade erythrocytes through endocytosis. Understanding these points will have a major effect on searching for new anti-malarial drug targets. Copyright © 2017 Elsevier B.V. All rights reserved.

Coalitional Physical Competition : Acute Salivary Steroid Hormone Responses among Juvenile Male Soccer Players in Hong Kong.

PubMed

McHale, Timothy S; Chee, Wai-Chi; Chan, Ka-Chun; Zava, David T; Gray, Peter B

2018-06-16

A large body of research links testosterone and cortisol to male-male competition. Yet, little work has explored acute steroid hormone responses to coalitional, physical competition during middle childhood. Here, we investigate testosterone, dehydroepiandrosterone (DHEA), androstenedione, and cortisol release among ethnically Chinese boys in Hong Kong (N = 102), aged 8-11 years, during a soccer match (n = 84) and an intrasquad soccer scrimmage (n = 81), with 63 participants competing in both treatments. The soccer match and intrasquad soccer scrimmage represented out-group and in-group treatments, respectively. Results revealed that testosterone showed no measurable change. DHEA increased during both treatments in the majority of participants and the degree of change had no relation to independent variables (e.g., performance, age, treatment, outcome) or covariate measures (Body Mass Index, Pubertal Development Scale). Most boys experienced androstenedione increases during match play, but no significant differences during the intrasquad soccer scrimmage competitions. The magnitude of change differed significantly between treatments and was positively associated with age. These latter findings suggest boys' androstenedione responses may be sensitive to competitor type (i.e., unknown competitors vs. peers). For most subjects, cortisol significantly increased during match play, decreased during the intrasquad soccer scrimmage, and differed significantly between treatments, suggesting each treatment promoted a different psychological state among competitors. Cortisol/DHEA molar ratio decreased during the intrasquad scrimmage, suggestive of a more relaxed mental state. These data shed new light on potential proximate mechanisms associated with coalitional competition among prepubescent boys, with relevance to adrenarche and life history theory.

The effects of a low-calorie diet or an isocaloric diet combined with metformin on sex hormones In obese women of child-bearing age.

PubMed

Swora-Cwynar, Ewelina; Kujawska-Łuczak, Magdalena; Suliburska, Joanna; Reguła, Julita; Kargulewicz, Angelika; Kręgielska-Narożna, Matylda; Marcinkowska, Emilia; Kanikowska, Alina; Bielas, Marzena; Grzymisławski, Marian; Bogdański, Paweł

2016-01-01

The influence of weight loss treatment on sex hormones profile has been studied mainly in women with polycystic ovary syndrome (PCOS), but in obese premenopausal women without PCOS it still remains unclear. The aim of the study was to evaluate the effect of two approaches to obesity treatment on the serum level of sex hormones in obese women of child-bearing age without PCOS. 77 obese Caucasian women (aged 31.2 ±8.3 years) were randomized into two groups: 39 women received a low-calorie diet (LC) and 38 received an isocaloric diet plus metformin (IM), for 12 weeks. Anthropometric parameters, body composition and serum concentrations of estradiol (E2), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and dehydroepiandrosterone (DHEA-S) sulfate were evaluated at baseline and after the study. Reductions in body weight, body mass index (BMI), waist and body fat content with an increase  in lean body percent were significant and comparable between the LC and IM group after the trial. The concentrations of serum FSH, LH, E2, DHEA and T did not change in either group after treatment. A tendency towards an increase in the E2 concentration in both groups and a decrease in the T level in the LC group  was observed. The correlations between a change in BMI, fat content, waist-hip ratio and a change in T were documented in the LC group. A 12-week low-calorie diet and an isocaloric diet combined with metformin produced comparable and significant weight loss with improvements in body composition. Both interventions did not significantly affect FSH, LH and DHEA sulfate serum concentrations, only a trend towards an E2 increase and a T decrease was observed, stronger in LC group. The significant correlations shown between the changes in anthropometric and body composition parameters and T serum levels in women treated with a low-calorie diet alone show the beneficial effect of a lifestyle intervention on the sex hormone in obese premenopausal women.

Endoxifen and Other Metabolites of Tamoxifen Inhibit Human Hydroxysteroid Sulfotransferase 2A1 (hSULT2A1)

PubMed Central

Squirewell, Edwin J.; Qin, Xiaoyan

2014-01-01

Although tamoxifen is a successful agent for treatment and prevention of estrogen-dependent breast cancer, its use has been limited by the low incidence of endometrial cancer. Human hydroxysteroid sulfotransferase 2A1 (hSULT2A1) catalyzes the formation of an α-sulfooxy metabolite of tamoxifen that is reactive toward DNA, and this has been implicated in its carcinogenicity. Also, hSULT2A1 functions in the metabolism of steroid hormones such as dehydroepiandrosterone (DHEA) and pregnenolone (PREG). These roles of hSULT2A1 in steroid hormone metabolism and in generating a reactive metabolite of tamoxifen led us to examine its interactions with tamoxifen and several of its major metabolites. We hypothesized that metabolites of tamoxifen may regulate the catalytic activity of hSULT2A1, either through direct inhibition or through serving as alternate substrates for the enzyme. We found that 4-hydroxy-N-desmethyltamoxifen (endoxifen) is a potent inhibitor of hSULT2A1-catalyzed sulfation of PREG and DHEA, with Ki values of 3.5 and 2.8 μM, respectively. In the hSULT2A1-catalyzed sulfation of PREG, 4-hydroxytamoxifen (4-OHTAM) and N-desmethyltamoxifen (N-desTAM) exhibited Ki values of 12.7 and 9.8 μM, respectively, whereas corresponding Ki values of 19.4 and 17.2 μM were observed with DHEA as substrate. A Ki value of 9.1 μM was observed for tamoxifen-N-oxide with DHEA as substrate, and this increased to 16.9 μM for the hSULT2A1-catalyzed sulfation of PREG. Three metabolites were substrates for hSULT2A1, with relative sulfation rates of 4-OHTAM > N-desTAM > > endoxifen. These results may be useful in interpreting ongoing clinical trials of endoxifen and in improving the design of related molecules. PMID:25157097

Hormonal determinants of the severity of andropausal and depressive symptoms in middle-aged and elderly men with prediabetes.

PubMed

Rabijewski, Michał; Papierska, Lucyna; Kuczerowski, Roman; Piątkiewicz, Paweł

2015-01-01

Andropausal and depressive symptoms are common in aging males and may be associated with hormone deficiency. We investigated the severity of andropausal and depressive symptoms, as well as their hormonal determinants, in 196 middle-aged and elderly men (age range: 40-80 years) with prediabetes (PD) and in 184 healthy peers. PD was diagnosed according to the definition of the American Diabetes Association. The severity of andropausal and depressive symptoms was assessed using the Aging Males' Symptoms Rating Scale and the Self-Rating Depression Scale. Total testosterone (TT), calculated free testosterone (cFT), dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF-1) were measured. The prevalence of andropausal syndrome in men with PD was significantly higher than that in healthy men (35% vs 11%, respectively). In men with PD aged 40-59 years, the severity of sexual, psychological, and all andropausal symptoms was greater than in healthy peers, while in elderly men (60-80 years), only the severity of psychological symptoms was greater than in healthy peers. The severity of depressive symptoms in the middle-aged men with PD was greater than in healthy peers, while the severity of depressive symptoms in elderly men with PD and healthy peers was similar. The higher prevalence of andropausal symptoms was independently associated with cFT and IGF-1 in middle-aged men and with TT and DHEAS in elderly men with PD. The more severe depression symptoms were associated with low TT and DHEAS in middle-aged men and with low cFT and DHEAS in elderly men with PD. In conclusion, the prevalence of andropausal symptoms, especially psychological, was higher in prediabetic patients as compared to healthy men, while the severity of depressive symptoms was higher only in middle-aged men with PD. Hormonal determinants of andropausal and depressive symptoms are different in middle-aged and elderly patients, but endocrine tests are necessary in all men with PD.

Hair cortisol concentration and glycated hemoglobin in African American adults.

PubMed

Lehrer, H Matthew; Dubois, Susan K; Maslowsky, Julie; Laudenslager, Mark L; Steinhardt, Mary A

2016-10-01

African Americans have higher diabetes prevalence compared to Whites. They also have elevated cortisol levels - indicating possible HPA axis dysregulation - which may raise blood glucose as part of the biological response to physiological and psychosocial stress. Little is known about chronic cortisol levels in African Americans, and even less about the role of chronically elevated cortisol in type 2 diabetes development in this racial group. We used analysis of cortisol in hair to examine associations of long-term (∼3months) cortisol levels with glycated hemoglobin (HbA1c) in a group of African American adults. In exploratory analyses, we also studied the relationship of hair dehydroepiandrosterone (DHEA) with HbA1c. Participants were 61 community-dwelling African American adults (85% female; mean age 54.30 years). The first 3cm of scalp-near hair were analyzed for cortisol and DHEA concentration using enzyme-linked immunoassay analysis. Glycated hemoglobin was assessed, and regression analyses predicting HbA1c from hair cortisol and DHEA were performed in the full sample and in a subsample of participants (n=20) meeting the National Institute of Diabetes and Digestive Kidney Disease (NIDDK) criteria for type 2 diabetes (HbA1c≥6.5%). In the full sample, HbA1c increased with hair cortisol level (β=0.22, p=0.04, f(2)=0.10), independent of age, sex, chronic health conditions, diabetes medication use, exercise, and depressive symptoms. In the subsample of participants with an HbA1c≥6.5%, hair cortisol was also positively related to HbA1c (β=0.45, p=0.04, f(2)=0.32), independent of diabetes medication use. Glycated hemoglobin was unrelated to hair DHEA in both the full sample and HbA1c≥6.5% subsample. Long-term HPA axis dysregulation in the form of elevated hair cortisol is associated with elevated HbA1c in African American adults. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study

PubMed Central

Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo; Bandinelli, Stefania; Basaria, Shehzad; Paolisso, Giuseppe; Ble, Alessandro; Egan, Josephine M.; Metter, E. Jeffrey; Abbatecola, Angela M.; Zuliani, Giovanni; Ruggiero, Carmelinda; Valenti, Giorgio; Guralnik, Jack M.; Ferrucci, Luigi

2009-01-01

Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (≥65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21–0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target

Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study.

PubMed

Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo; Bandinelli, Stefania; Basaria, Shehzad; Paolisso, Giuseppe; Ble, Alessandro; Egan, Josephine M; Metter, E Jeffrey; Abbatecola, Angela M; Zuliani, Giovanni; Ruggiero, Carmelinda; Valenti, Giorgio; Guralnik, Jack M; Ferrucci, Luigi

2007-01-01

Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (>/=65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21-0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target

Ingesting alcohol prior to food can alter the activity of the hypothalamic-pituitary-adrenal axis.

PubMed

Kokavec, Anna; Lindner, Amy J; Ryan, Jaymee E; Crowe, Simon F

2009-08-01

There is an increasing evidence that long-term alcohol intake can promote damage to most of the body's major organs. However, regular consumption of a small-moderate amount of alcohol is often recommended as being beneficial to health and of concern is that the effect of ingesting commercially available alcohol products on steroid hormone synthesis under variable nutritional conditions has not been thoroughly investigated. Many individuals consume alcohol alone prior to a meal and the aim of the present study was to assess the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary cortisol and salivary dehydroepiandrosterone sulfate (DHEAS) before and after a meal. A total of 24 males aged 19-22 years participated in the current investigation. The experimental procedure required participants to fast for 6 h before being asked to ingest either 40 g alcohol in the form of red wine (n=8), low alcohol and high beer (n=8), white wine (n=8) or the equivalent amount of placebo over a 135-min period before consuming food for 45-min. The level of blood alcohol, salivary cortisol and salivary DHEAS was assessed upon arrival and then at regular 45-min intervals during the 180-min experimental period. The results showed that the consumption of alcohol and placebo can significantly lower the level of salivary cortisol. However, the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary DHEAS was dependent on the nutritional content of the beverage with red wine promoting no change, white wine promoting a significant decrease, and beer having a variable effect on salivary DHEAS concentration when compared to placebo. It was concluded that the effect of commercially available alcohol on the HPA axis is not the same for all alcohol products and both the nutritional status of participants and the nutritional content of the alcoholic beverage being administered should be taken into

The utility and dynamics of salivary sex hormone measurements in the National Social Life, Health, and Aging Project, Wave 2.

PubMed

Kozloski, Michael J; Schumm, L Philip; McClintock, Martha K

2014-11-01

Sex hormones affect physical, mental, and social health, yet their role in mediating social effects on aging is understudied. To facilitate such analyses with the National Social Life, Health & Aging Project Wave 2, we summarize the conceptual background, collection protocols, laboratory assays, and data analysis strategies for biologically active (free) levels of testosterone, estradiol, progesterone, and dehydroepiandrosterone (DHEA). Saliva from passive drool was collected from returning Wave 1 respondents and non-respondents as well as their partners during an in-home interview. Specimens were frozen and sent to Dresden LabService GmbH for duplicate assays of biologically active steroids using identical assay kits from National Social Life, Health, and Aging Project (NSHAP) Wave 1 (SaliCap, Catalog No. RE69995). Overall, 2,772 testosterone, 2,504 estradiol, 2,714 progesterone, and 2,800 DHEA measurements are publically available for Wave 2 analyses. Through a series of weighted linear regressions, all 4 steroids are compared by gender and age and to Wave 1 measurements. Men had higher levels of both free testosterone and progesterone than women; women and men had the same levels of estradiol and DHEA. Both free testosterone and DHEA decreased with age. We also found significant wave effects for all 4 sex hormones. NSHAP Waves 1 and 2 are the first U.S. probability sample studies to measure these 4 salivary sex hormones simultaneously, providing individual profiles 5 years apart. Wave 2 data demonstrate differences by gender and trends by age that are similar to those found in other saliva-based and serum-based studies of free steroid levels. The differences between waves arising from the change in assay laboratory need to be adjusted in future longitudinal analyses using NSHAP Wave 1 and Wave 2 steroid data. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e

DHEAS Test

MedlinePlus

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Ethnic differences in DNA methyltransferases expression in patients with systemic lupus erythematosus.

PubMed

Wiley, Kenneth L; Treadwell, Edward; Manigaba, Kayihura; Word, Beverly; Lyn-Cook, Beverly D

2013-02-01

Systemic lupus erythematous (SLE) is a systemic autoimmune inflammatory disease with both genetic and epigenetic etiologies. Evidence suggests that deregulation of specific genes through epigenetic mechanisms may be a contributing factor to SLE pathology. There is increasing evidence that DNA methyltransferase activity may be involved. This study demonstrated modulation in expression of DNA methyltransferases (DNMTs) according to ethnicity in patients diagnosed with SLE. Furthermore, differential expression in one of the DNMTs was found in a subset of lupus patients on dehydroepiandrosterone (DHEA) therapy. Real-time PCR analyses of DNMT1, DNMT3A and DNMT3B in peripheral blood mononuclear cells from a cohort of African American and European American lupus and non-lupus women were conducted. Also, global DNA methylation was assessed using the MethylFlash(TM) methylated quantification colorimetric assay. Significant increase in DNMT3A (p < 0.001) was shown in lupus patients when compared to age-matched healthy controls. This increase was associated with a higher SLEDI index. More striking was that expression levels for African American (AA) women were higher than European American women in the lupus populations. A subset of AA women on DHEA therapy showed a significant decrease (p < 0.05) in DNMT3A expression in comparison to lupus patients not on the therapy. DHEA is an androgenic steroid found in low levels in the serum of lupus patients. Supplementation of this hormone has been shown to be beneficial to some lupus patients. DHEA was not shown to effect DNMT1 or DNMT3B expression. Increased expression was also noted in DNMT3B (p < 0.05) in lupus patients compared to age-matched healthy controls. However, no significant difference was noted in DNMT1 (p = 0.2148) expression between lupus patients and healthy controls. Although increases were detected in de novo methyltransferases, a global decrease (p < 0.001) in 5-methycytosine was observed in

The effects of oral contraceptives on androgen levels and their relevance to premenstrual mood and sexual interest: a comparison of two triphasic formulations containing norgestimate and either 35 or 25 microg of ethinyl estradiol.

PubMed

Greco, Teri; Graham, Cynthia A; Bancroft, John; Tanner, Amanda; Doll, Helen A

2007-07-01

This study compared two oral contraceptives (OCs) with the same triphasic regimen of progestin (norgestimate 0.18, 0.215 and 0.25 mg) but differing doses of ethinyl estradiol (EE) - 25 and 35 microg EE - in their effects on androgens, mood and sexual interest in women starting on OCs. Total testosterone (T), free testosterone (FT), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone sulphate (DHEA-S), together with measures of mood [Beck Depression Inventory (BDI)], sexual interest [Dyadic and Solitary subscales of the Sexual Desire Inventory (SDI)] and self-reported side effects were assessed before starting on the OC and again after 3 months of use. Sixty women, all university students, were randomized to receive either the 25 microg EE (N/EE25) or the 35 microg EE (N/EE35) pill; 12 women discontinued, leaving 48 who completed the 3-month study. Their mean age was 19.7 years (18-30) and they were predominantly white and single. Both OCs produced reductions in mean T [N/EE35: from 1.33 to 0.60 nmol/L, p<.001; N/EE25: from 1.12 to 1.02 nmol/L; nonsignificant (NS)] and FT (N/EE35: from 41.3 to 4.4 pmol/L, p<.001; N/EE25: from 25.4 to 7.9 pmol/L, p<.01), but the reduction in both T and FT was significantly greater with the higher EE dose (N/EE35) (p=.05 and p=.03, respectively). DHEA-S was also reduced with both formulations (N/EE35: from 7.26 to 5.22 micromol/L); N/EE25: from 7.50 to 5.39 micromol/L), although the reduction was only significant in the N/EE35 group (p<.02). Considerable variability in changes in mood was evident with both OCs, with some women showing predominantly negative effects (10 in N/EE35, 5 in N/EE25); others, positive effects (9 in N/EE35, 17 in N/EE25) and some, no change (four in each group). Women using N/EE25 were significantly more likely to show improvement in premenstrual mood than those in the N/EE35 group (p<.02), although there was no correlation between changes in BDI and FT or DHEA-S. Sexual interest scores did not

Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls.

PubMed

Watkins, Deborah J; Sánchez, Brisa N; Téllez-Rojo, Martha Maria; Lee, Joyce M; Mercado-García, Adriana; Blank-Goldenberg, Clara; Peterson, Karen E; Meeker, John D

2017-11-01

Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. We measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8-13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes. Several phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13-83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (ΣDEHP) specifically in the third trimester

Psychobiological Protective Factors Modifying the Association Between Age and Sexual Health in Men: Findings From the Men’s Health 40+ Study

PubMed Central

Walther, Andreas; Mahler, Fiona; Debelak, Rudolf; Ehlert, Ulrike

2017-01-01

Sexual health severely decreases with age. For males older than 40 years, erectile dysfunction (ED) is the most common sexual disorder. Although physical and psychological risk factors for ED have been identified, protective factors are yet to be determined. To date, no study has examined endocrine and psychosocial factors in parallel with regard to their modifying effect on the age-related increase in ED. Two hundred and seventy-one self-reporting healthy men aged between 40 and 75 years provided both psychometric data on sexual function and a set of potential psychosocial protective factors, and saliva samples for the analysis of steroid hormones and proinflammatory cytokines. Around 35% of the participants reported at least a mild form of ED. Direct associations with ED were identified for perceived general health, emotional support, relationship quality, intimacy motivation but not for steroid hormones or proinflammatory markers. Moderation analyses for the association between age and ED revealed positive effects for testosterone (T), dehydroepiandrosterone (DHEA), perceived general health, emotional support, intimacy motivation, and a negative effect for interleukin-6 (all p < .05; f2 > .17). Group differences between older men with and without ED emerged for T, DHEA, and psychometric measures such as perceived general health, emotional support, satisfaction with life, and intimacy motivation (all p < .05; d > .3). Both psychosocial and endocrine parameters moderated the association between age and sexual health. Perceived general health, emotional support, intimacy motivation, and relationship quality emerged as psychosocial protective factors against ED. Higher T and DHEA and lower interleukin-6 levels also buffered against an age-related increase in ED. PMID:28413941

Depressive symptoms are associated with reduced neutrophil function in hip fracture patients☆

PubMed Central

Duggal, Niharika Arora; Upton, Jane; Phillips, Anna C.; Hampson, Peter; Lord, Janet M.

2013-01-01

Hip fracture is a common trauma in older adults with a high incidence of depression, which relates to poorer prognosis including increased risk of infection. Ageing is accompanied by reduced immunity, termed immunesenescence, resulting in increased susceptibility to infection. We examined whether physical trauma (hip fracture) and psychological distress (depressive symptoms) had additive effects upon the aged immune system that might contribute to poor outcomes after injury. Neutrophil function was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched controls (28 female). Thirty eight fracture patients had depressive symptoms at 6 weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed between controls and hip fracture patients, but superoxide production was significantly reduced in hip fracture patients with depressive symptoms compared with patients without symptoms (p = .001) or controls (p = .004) at 6 weeks. Superoxide production improved 6 months following fracture to the level seen in controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with depressive symptoms compared with patients without depressive symptoms or controls at 6 weeks and 6 months after injury. Serum IL6, TNFα and IL10 were higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS ratio and IL6 levels related to depressive symptom scores but not to neutrophil function. In conclusion, depressive symptoms related to poorer neutrophil function after hip fracture, but this was not driven by changes in stress hormone or cytokine levels. PMID:23876747

The influence of combined oral contraceptives containing drospirenone on hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome.

PubMed

Macut, Djuro; Božić Antić, Ivana; Nestorov, Jelena; Topalović, Vladanka; Bjekić Macut, Jelica; Panidis, Dimitrios; Kastratović Kotlica, Biljana; Papadakis, Efstathios; Matić, Gordana; Vojnović Milutinović, Danijela

2015-01-01

Most women with PCOS have increased adrenal androgen production, enhanced peripheral metabolism of cortisol and elevation in urinary excretion of its metabolites. Increased cortisol clearance in PCOS is followed by a compensatory overdrive of the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that oral contraceptives containing ethinylestradiol and drospirenone (EE-DRSP) could modulate glucocorticoid receptor (GR) expression and function and thus affect HPA axis activity in PCOS patients. We analyzed 12 women with PCOS (age 24.17±4.88 years; body mass index 22.05±3.97 kg/m²) treated for 12 months with EE-DRSP and 20 BMI matched controls. In all subjects testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), cortisol (basal and after dexamethasone), concentrations of GR protein, phospo-GR211 protein, number of GR per cell (B(max) and its equilibrium dissociation constant (K(D)) were measured. Before treatment, increased concentrations of testosterone and DHEAS (p<0.001, respectively), unaltered basal cortisol and an increased sensitivity (p<0.05) of the HPA axis to dexamethasone were observed in PCOS women in comparison to controls. After treatment, testosterone (p<0.01), DHEAS (p<0.05) and cortisol suppression after dexamethasone (p<0.01) were decreased in PCOS women. There were no changes in GR protein concentration, GR phosphorylation nor in the receptor functional parameters B(max) and K(D) in women with PCOS before and after the therapy, and in comparison to controls. Prolonged treatment with EE-DRSP in PCOS women decreased serum androgens and increased cortisol in the presence of decreased sensitivity of the HPA axis and did not exert changes in GR expression and function.

Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

PubMed

MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

2007-12-01

In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration.

β3-Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats.

PubMed

Csanova, Agnesa; Hlavacova, Natasa; Hasiec, Malgorzata; Pokusa, Michal; Prokopova, Barbora; Jezova, Daniela

2017-05-01

The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β 3 -adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β 3 -receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β 3 -receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in β 3 -adrenergic receptor gene expression in the brain. Greater reduction of β 3 -adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of β 3 -adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections.

Adrenal Hyperandrogenism and Polycystic Ovary Syndrome.

PubMed

Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2016-01-01

The prevalence of adrenal hyperandrogenism (AH), as defined by increased circulating dehydroepiandrosterone-sulfate (DHEAS) levels, ranges from 15 to 45% in women with polycystic ovary syndrome (PCOS). The aim of this review is to update the pathogenesis and consequences of AH in PCOS, from molecular genetics to the clinical setting. Mounting evidence derived from animal models suggests that genetically or enviromentally determined prenatal androgen excess, by influencing the hormonal and metabolic phenotype of susceptible female fetuses later in life, may be the capital event for the development of AH in PCOS. Because human placental aromatase activity is likely to prevent any deleterious effect of maternal hyperandrogenemia on the fetus, inheritance of the maternal steroidogenic defect is the more likely culprit, even though other factors such as changes in placental steroidogenesis itself or its nutritional efflux may also be involved in the building a deregulated enzymatic pathway from utero to adult life. Anyhow, the most important issue is whether or not AH influences the cardiometabolic risk of women with PCOS. On the one hand, AH has shown a controversial relationship with carbohydrate metabolism and adiposity, and is also associated with abnormalities in blood pressure regulation in these patients. On the other hand, DHEAS may exert a beneficial effect on the lipid profile of both lean and obese patients. Lastly, available studies in women with PCOS cast doubt upon a protective role of DHEAS levels on subclinical atherosclerosis, despite opposite data from the general population. AH is frequent in patients with PCOS yet unraveling its consequences for the management of this disorder requires future longitudinal studies.

Association Between Hormones and Metabolic Syndrome in Older Italian Men

PubMed Central

Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo; Bandinelli, Stefania; Basaria, Shehzad; Ble, Alessandro; Egan, Josephine; Paolisso, Giuseppe; Najjar, Samer; Metter, E. Jeffrey; Valenti, Giorgio; Guralnik, Jack M.; Ferrucci, Luigi

2009-01-01

OBJECTIVES To determine whether low levels of testosterone, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and dehydroepiandrosterone sulfate (DHEAS) and high levels of cortisol and leptin would be associated with metabolic syndrome (MS). DESIGN Cross-sectional. SETTING Population-based sample of older Italian men. PARTICIPANTS Four hundred fifty-two men aged 65 and older enrolled in the Invecchiare in Chianti (InCHIANTI) study. MEASUREMENTS Complete data on testosterone, cortisol, DHEAS, SHBG, fasting insulin, IGF-1 and leptin. MS was defined according to Adult Treatment Panel III criteria. RESULTS MS was present in 73 men (15.8% of the sample). After adjusting for confounders, total testosterone (P<.05) and log (SHBG) (P<.001) were inversely associated, whereas log (leptin) was positively associated with MS (P<.001). Independent of age, log (SHBG) was positively associated with high-density lipoprotein cholesterol (P<.05) and negatively associated with abdominal obesity (P<.001) and triglycerides (P<.001). Log (leptin) was significantly associated with each component of MS. Cortisol, DHEAS, free and bioavailable testosterone, and IGF-1 were not associated with MS. Having three or more hormones in the lower (for hormones lower in MS) or the upper (for hormones higher in MS) quartile was associated with three times the risk of being affected by MS (odds ratio =2.8, 95% confidence interval =1.3–6.9) (P=.005), compared with not having this condition. CONCLUSION Total testosterone and SHBG are negatively and leptin is positively associated with MS in older men. Whether specific patterns of hormonal dysregulation predict the development of MS should be tested in longitudinal studies. PMID:17198487

Intergenerational gene × environment interaction of FKBP5 and childhood maltreatment on hair steroids.

PubMed

Koenig, Alexandra M; Ramo-Fernández, Laura; Boeck, Christina; Umlauft, Maria; Pauly, Markus; Binder, Elisabeth B; Kirschbaum, Clemens; Gündel, Harald; Karabatsiakis, Alexander; Kolassa, Iris-Tatjana

2018-06-01

The inconsistency in results of cortisol alterations after childhood maltreatment (CM) might arise due to the fact that no study so far considered the effects of environmental factors such as maltreatment load and genetic factors such as the influence of FKBP5 genotype on stress hormone regulation. This study analyzed the interaction between the single nucleotide polymorphism rs1360780 within the FKBP5 gene and the severity of maternal CM experiences (maltreatment load) on hair steroid levels of mother-infant-dyads. Hair samples of N = 474 mothers and N = 331 newborns were collected < 1 week after parturition enabling a retrospective assessment of cortisol, cortisone, and dehydroepiandrosterone (DHEA) using mass spectrometry. The sum score of the Childhood Trauma Questionnaire operationalized the maternal maltreatment load. DNA from whole blood or buccal cells was used for FKBP5 genotyping. The higher the maltreatment load, the higher maternal hair cortisol and cortisone levels in T allele carriers of FKBP5 rs1360780 were observed. Hair cortisol and DHEA levels of newborns with the T allele were reduced with an increasing maternal maltreatment load, while there was an increase of hair cortisol and DHEA in newborns homozygous for the C allele. This study is the very first uncovering a gene (FKBP5) × environment (maltreatment load) interaction on hair steroids in mothers and their offspring, indicating an intergenerational transmission of hypothalamic-pituitary-adrenal axis alterations. These results may help to explain the inconsistency in previous findings on steroid hormone alterations after chronic and traumatic stress and should be considered in future studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Prevalence and metabolic characteristics of adrenal androgen excess in hyperandrogenic women with different phenotypes.

PubMed

Carmina, E; Lobo, R A

2007-02-01

Serum DHEAS has been found to be elevated in some women with polycystic ovary syndrome (PCOS). We wished to determine whether this prevalence is different in women with androgen excess who have different phenotypes and to correlate these findings with various cardiovascular and metabolic parameters. Two hundred and thirty-eight young hyperandrogenic women categorized into various diagnostic groups were evaluated for elevations in serum DHEAS, testosterone, glucose, insulin, quantitative insulin-sensitivity check index (QUICKI), cholesterol, HDL-C, LDL-C, triglycerides and C-reactive protein (CRP). Data were stratified based on elevations in DHEAS. Serum DHEAS was elevated in 39.5% for the entire group [36.7% in PCOS and 48.3% in idiopathic hyperandrogenism (IHA)]. In classic (C)-PCOS, the prevalence was 39.6% and in ovulatory (OV) PCOS it was 29.1%. These differences were not statistically significant. Women with elevated DHEAS had higher testosterone but lower insulin, higher QUICKI, lower total and LDL-cholesterol and higher HDL-cholesterol, p<0.01. Triglycerides and CRP were not different. This trend was greatest in women with C-PCOS. The prevalence of adrenal hyperandrogenism, as determined by elevations in DHEAS, appears to be statistically similar in IHA, C-PCOS and compared to OV-PCOS. Metabolic and cardiovascular parameters were noted to be more favorable in those women who have higher DHEAS levels.

Induction of hyperandrogenism in lean reproductive-age women stimulates proatherogenic inflammation.

PubMed

González, F; Sreekumaran Nair, K; Basal, E; Bearson, D M; Schimke, J M; Blair, H E

2015-06-01

We determined the effect of hyperandrogenemia as observed in polycystic ovary syndrome (PCOS) on fasting and glucose-stimulated proatherogenic inflammation markers in lean healthy reproductive-age women. Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n=8 each) for 5 days. Interleukin-6 (IL-6) mRNA and IL-6 release from mononuclear cells (MNC), plasma IL-6 and C-reactive protein (CRP), and MNC-derived (matrix metalloproteinase-2) MMP-2 protein were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment. Before treatment, subjects receiving dehydroepinadrosterone (DHEA) or placebo exhibited no differences in androgens, or any proatherogenic inflammation markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate (DHEA-S), and increased the percent change from baseline in fasting IL-6 mRNA, IL-6 release, plasma IL-6, and CRP and MMP-2 protein. However, there were no differences in any of the proatherogenic inflammation markers following glucose ingestion after DHEA administration. We conclude that in lean reproductive-age women, proatherogenic inflammation in the fasting state increases after raising circulating androgens to levels observed in PCOS. However, this hyperandrogenemia-induced MNC activation does not provoke a similar response to subsequent glucose ingestion. © Georg Thieme Verlag KG Stuttgart · New York.

Does endogenous serum oestrogen play a role in meibomian gland dysfunction in postmenopausal women with dry eye?

PubMed

Golebiowski, Blanka; Badarudin, Noor; Eden, John; You, Jingjing; Hampel, Ulrike; Stapleton, Fiona

2017-02-01

To explore the relationship between serum concentration of sex hormones and dry eye symptoms and signs in postmenopausal women. A cross-sectional analysis was undertaken. Subjects were 46 postmenopausal women with dry eye (mean age 64.4±5.2 years, 13.7±6.4 years since menopause; not undergoing hormone replacement therapy). Ocular symptoms (Ocular Surface Disease Index (OSDI) and Ocular Comfort Index (OCI)), tear function (tear osmolarity, non-invasive tear break-up time, tear secretion), corneal and conjunctival staining, and meibomian gland (MG) appearance, were recorded. Venous blood was collected and serum concentrations of 17β-oestradiol (E2), 3-α-androstanediol-glucuronide (3α-diol-G), and dehydroepiandrosterone sulfate (DHEA-S) were determined using ELISA. Multiple linear regression analysis was used to examine predictors of dry eye symptoms and signs. Mean serum concentration of E2, 3α-diol-G and DHEA-S was 9.02±13.40 pg/mL, 1.59±1.02 ng/mL and 0.74±0.53 μg/mL, respectively. Ocular symptoms were elevated (mean scores 27.0±18.1 (OSDI) and 40.3±8.4 (OCI)) but signs were within normal ranges. Higher serum E2 concentration along with capped glands, lid telangiectasia and older age was a significant predictor of worse MG secretion quality (p<0.001, R 2 adj=0.75). Serum hormones were not significant predictors of ocular symptoms in multivariate analysis (p>0.05). Serum oestrogen appears to be a key factor in MG signs. Although serum hormone levels did not contribute significantly to dry eye symptoms in this study, it is possible that oestrogen plays a role through its effect on meibum secretion. These findings suggest that MG dysfunction underpins dry eye symptoms in non-Sjögren's dry eye in postmenopausal women. ACTRN12612000281897. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effects of heat stress on endocrine functions & behaviour in the pre-pubertal rat.

PubMed

Mete, Fatih; Kilic, Ertugrul; Somay, Adnan; Yilmaz, Bayram

2012-01-01

Heat stress related hyperthermia may cause damage to various organ systems. There are very few studies on the effects of hyperthermia on the endocrine system. We therefore, investigated effects of exogenously induced hyperthermia on adrenal, testicular and thyroid functions and behavioural alterations in pre-pubertal male Sprague-Dawley rats. Three groups of 30-day old rats (n=7 per group) were used. Body temperature was increased to 39 °C (Group I) and 41 °C (Group II) in a hyperthermia induction chamber for 30 min. The rats in the Group III served as control (36 °C). All animals received saline and were decapitated 48 h after the experiments. Serum free triiodothyronin (fT3), free thyroxine (fT4), total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were determined by chemiluminescence assay, and corticosterone by enzyme immunoassay. Testes, pituitary and adrenal glands were dissected out and processed for histopathological examination. To assess activity and anxiety of the animals, the open field test and elevated-0-maze test, respectively, were used in all groups 24 h before (day 29) and after (day 31) hyperthermia induction. Serum corticosterone levels (3.22 ± 1.3) were significantly reduced in the 39 °C (1.3 ± 0.9) and 41 °C (1.09 ± 0.7) hyperthermia groups (P<0.01) compared to controls. Serum levels of thyroid hormones did not significantly differ among the groups. DHEA-S and testosterone values were below the limit of detection in all groups. Histopathological examination revealed that there was mild hydropic degeneration in the pituitary and adrenal glands. Apoptotic germ cells were seen in the seminiferous tubules of pre-pubertal male rats exposed to hyperthermia (41 °C). Progression time in the open field test was significantly decreased and anxiety test scores increased in animals exposed to 39 °C compared to the control group (P<0.01). These parameters were more pronounced in the 41 °C hyperthermia group. Our results show

Effects of heat stress on endocrine functions & behaviour in the pre-pubertal rat

PubMed Central

Mete, Fatih; Kilic, Ertugrul; Somay, Adnan; Yilmaz, Bayram

2012-01-01

Background & objectives: Heat stress related hyperthermia may cause damage to various organ systems. There are very few studies on the effects of hyperthermia on the endocrine system. We therefore, investigated effects of exogenously induced hyperthermia on adrenal, testicular and thyroid functions and behavioural alterations in pre-pubertal male Sprague-Dawley rats. Methods: Three groups of 30-day old rats (n=7 per group) were used. Body temperature was increased to 39°C (Group I) and 41°C (Group II) in a hyperthermia induction chamber for 30 min. The rats in the Group III served as control (36 °C). All animals received saline and were decapitated 48 h after the experiments. Serum free triiodothyronin (fT3), free thyroxine (fT4), total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were determined by chemiluminescence assay, and corticosterone by enzyme immunoassay. Testes, pituitary and adrenal glands were dissected out and processed for histopathological examination. To assess activity and anxiety of the animals, the open field test and elevated-0-maze test, respectively, were used in all groups 24 h before (day 29) and after (day 31) hyperthermia induction. Results: Serum corticosterone levels (3.22±1.3) were significantly reduced in the 39°C (1.3±0.9) and 41°C (1.09±0.7) hyperthermia groups (P<0.01) compared to controls. Serum levels of thyroid hormones did not significantly differ among the groups. DHEA-S and testosterone values were below the limit of detection in all groups. Histopathological examination revealed that there was mild hydropic degeneration in the pituitary and adrenal glands. Apoptotic germ cells were seen in the seminiferous tubules of pre-pubertal male rats exposed to hyperthermia (41°C). Progression time in the open field test was significantly decreased and anxiety test scores increased in animals exposed to 39°C compared to the control group (P<0.01). These parameters were more pronounced in the 41�

The relevance of chemical interactions with CYP17 enzyme activity: Assessment using a novel in vitro assay

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

Roelofs, Maarke J.E., E-mail: m.j.e.roelofs@uu.nl; Center for Health Protection, National Institute for Public Health and the Environment; Piersma, Aldert H.

The steroidogenic cytochrome P450 17 (CYP17) enzyme produces dehydroepiandrosterone (DHEA), which is the most abundant circulating endogenous sex steroid precursor. DHEA plays a key role in e.g. sexual functioning and development. To date, no rapid screening assay for effects on CYP17 is available. In this study, a novel assay using porcine adrenal cortex microsomes (PACMs) was described. Effects of twenty-eight suggested endocrine disrupting compounds (EDCs) on CYP17 activity were compared with effects in the US EPA validated H295R (human adrenocorticocarcinoma cell line) steroidogenesis assay. In the PACM assay DHEA production was higher compared with the H295R assay (4.4 versus 2.2more » nmol/h/mg protein). To determine the additional value of a CYP17 assay, all compounds were also tested for interaction with CYP19 (aromatase) using human placental microsomes (HPMs) and H295R cells. 62.5% of the compounds showed enzyme inhibition in at least one of the microsomal assays. Only the cAMP inducer forskolin induced CYP17 activity, while CYP19 was induced by four test compounds in the H295R assay. These effects remained unnoticed in the PACM and HPM assays. Diethylstilbestrol and tetrabromobisphenol A inhibited CYP17 but not CYP19 activity, indicating different mechanisms for the inhibition of these enzymes. From our results it becomes apparent that CYP17 can be a target for EDCs and that this interaction differs from interactions with CYP19. Our data strongly suggest that research attention should focus on validating a specific assay for CYP17 activity, such as the PACM assay, that can be included in the EDC screening battery. - Highlights: ► DHEA, produced by CYP17, plays a key role in sexual functioning and development. ► No rapid screening assay for effects on CYP17 is available yet. ► A novel assay using porcine adrenal cortex microsomes (PACMs) was described. ► Endocrine disrupting compounds (EDCs) targeting CYP17 interact differently with CYP19. ► A

Care Transitions and Adult Day Services Moderate the Longitudinal Links between Stress Biomarkers and Family Caregivers' Functional Health.

PubMed

Liu, Yin; Almeida, David M; Rovine, Michael J; Zarit, Steven H

2017-01-01

Stress biomarkers have been linked to health and well-being. There are, however, few studies on how dysregulation in the hypothalamic-pituitary-adrenal axis and sympathetic nervous system actually affects functional health of family caregivers of persons with dementia. Further, it is not clear whether and how factors affecting caregiving stressor exposures such as care transitions and adult day services (ADS) use may affect such association. First, to examine the association of daily stress biomarkers and functional health over time among family caregivers of persons with dementia. Second, to examine effects of care transitions and ADS use on the association between baseline stress biomarkers and functional health over time. At baseline, caregivers provided 5 saliva samples each day during an 8-day diary study, where all caregivers were having a varying number of ADS days per week. There were 2 longitudinal follow-ups at 6 and 12 months on ADS use, care transitions, and caregivers' functional health. The average daily total output across days was computed at baseline for salivary cortisol, the sulfated form of dehydroepiandrosterone (DHEA-s), and salivary alpha amylase (sAA), which were used as predictors of caregivers' longitudinal functional limitation trajectories. Care transitions and total number of ADS days per week at baseline were considered as moderators of the associations between stress biomarkers and health over time. The associations between functional limitation trajectories and daily total outputs of cortisol and sAA were modified by ADS use and care transitions. Among caregivers who experienced a transition, and who used less than average ADS days per week, lower daily cortisol total output and lower daily sAA total output were associated with increasing functional limitations. Caregivers who experienced a transition but used greater than average ADS days per week did not show such patterns of association. No significant effect was found for DHEA-s

Proinflammatory and anti-inflammatory cytokine changes related to menopause

PubMed Central

Malutan, Andrei Mihai; Nicolae, Costin; Carmen, Mihu

2014-01-01

The aim of the study The aim of the study was to determine menopause-related changes in serum levels of main proinflammatory and anti-inflammatory cytokines. Material and methods The study included 175 women, who were divided into 5 study groups (group 1 – fertile women; group 2 – pre- and perimenopausal women; group 3 – postmenopausal women; group 4 – surgically induced menopausal women; group 5 – women with chronic inflammatory pathology). We evaluated the serum levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IL-20 and of the tumour necrosis factor (TNF)α with the use of two multiplex cytokine kits. We also determined the serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol (17β-E2), progesterone (P), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) using sandwich ELISA. Results The serum level of IL-1β, IL-8 and TNF-α in women with natural menopause and in women with surgically induced menopause is significantly higher than in fertile women in the control group. In patients with surgically induced menopause and in women with natural menopause, IL-8 serum levels are similar to those seen in patients with chronic inflammatory diseases. There is a statistically significant decrease in serum levels of IL-20 in women with natural or surgical menopause than in fertile and premenopausal women. Conclusions Women in menopause have elevated levels of the key proinflammatory cytokines, i.e. IL-1β, IL-8 and TNF-α and low serum levels of IL-20 in comparison with fertile women. PMID:26327849

Free androgen index and Irisin in polycystic ovary syndrome.

PubMed

Li, H; Xu, X; Wang, X; Liao, X; Li, L; Yang, G; Gao, L

2016-05-01

PCOS is associated with hyperandrogenism and insulin resistance (IR). Recent studies have shown that circulating Irisin levels increase in PCOS women. However, no report has demonstrated a relationship between Irisin and hyperandrogenism in PCOS women. The purpose of the study was to compare interrelationship between Irisin or androgen excess with IR in PCOS and normal subjects. 166 PCOS and 103 control women were prospectively studied. Euglycemic- hyperinsulinemic clamps were preformed to assess their insulin sensitivity, which was expressed as M value. Circulating Irisin was determined by ELISA kit. Circulating androgens were measured using ultrasensitive assays. PCOS women with high FAI had significantly higher BMI, FAT%, TC, DHEA-S and HOMA-IR, and significantly lower levels of M values and SHBG than PCOS women with low FAI or the controls. Pearson correlations showed that in the entire population, FAI correlated positively with BMI, WHR, FAT%, blood pressure, TG, DHEA-S, LH/FSH, AUCinsulin, HOMA-IR and Irisin, and negatively with M values. In multiple stepwise regression analysis, only FAT%, DHEA-S and LH/FSH were independent related factors with FAI. The elevated Irisin levels in PCOS women were associated with androgen excess. Circulating Irisin is a primary predictor of hyperandrogenism, MetS and IR in PCOS women.

Biological mechanisms associated with increased perseveration and hyperactivity in a genetic mouse model of neurodevelopmental disorder

PubMed Central

Trent, Simon; Dean, Rachel; Veit, Bonnie; Cassano, Tommaso; Bedse, Gaurav; Ojarikre, Obah A.; Humby, Trevor; Davies, William

2013-01-01

Summary Chromosomal deletions at Xp22.3 appear to influence vulnerability to the neurodevelopmental disorders attention deficit hyperactivity disorder (ADHD) and autism. 39,XY*O mice, which lack the murine orthologue of the Xp22.3 ADHD candidate gene STS (encoding steroid sulfatase), exhibit behavioural phenotypes relevant to such disorders (e.g. hyperactivity), elevated hippocampal serotonin (5-HT) levels, and reduced serum levels of dehydroepiandrosterone (DHEA). Here we initially show that 39,XY*O mice are also deficient for the recently-characterised murine orthologue of the Xp22.3 autism candidate gene ASMT (encoding acetylserotonin-O-methyltransferase). Subsequently, to specify potential behavioural correlates of elevated hippocampal 5-HT arising due to the genetic lesion, we compared 39,XY*O MF1 mice to 40,XY MF1 mice on behavioural tasks taxing hippocampal and/or 5-HT function (a ‘foraging’ task, an object-location task, and the 1-choice serial reaction time task of impulsivity). Although Sts/Asmt deficiency did not influence foraging behaviour, reactivity to familiar objects in novel locations, or ‘ability to wait’, it did result in markedly increased response rates; these rates correlated with hippocampal 5-HT levels and are likely to index behavioural perseveration, a frequent feature of neurodevelopmental disorders. Additionally, we show that whilst there was no systematic relationship between serum DHEA levels and hippocampal 5-HT levels across 39,XY*O and 40,XY mice, there was a significant inverse linear correlation between serum DHEA levels and activity. Our data suggest that deficiency for genes within Xp22.3 could influence core behavioural features of neurodevelopmental disorders via dissociable effects on hippocampal neurochemistry and steroid hormone levels, and that the mediating neurobiological mechanisms may be investigated in the 39,XY*O model. PMID:23276394

Biological mechanisms associated with increased perseveration and hyperactivity in a genetic mouse model of neurodevelopmental disorder.

PubMed

Trent, Simon; Dean, Rachel; Veit, Bonnie; Cassano, Tommaso; Bedse, Gaurav; Ojarikre, Obah A; Humby, Trevor; Davies, William

2013-08-01

Chromosomal deletions at Xp22.3 appear to influence vulnerability to the neurodevelopmental disorders attention deficit hyperactivity disorder (ADHD) and autism. 39,X(Y*)O mice, which lack the murine orthologue of the Xp22.3 ADHD candidate gene STS (encoding steroid sulfatase), exhibit behavioural phenotypes relevant to such disorders (e.g. hyperactivity), elevated hippocampal serotonin (5-HT) levels, and reduced serum levels of dehydroepiandrosterone (DHEA). Here we initially show that 39,X(Y*)O mice are also deficient for the recently-characterised murine orthologue of the Xp22.3 autism candidate gene ASMT (encoding acetylserotonin-O-methyltransferase). Subsequently, to specify potential behavioural correlates of elevated hippocampal 5-HT arising due to the genetic lesion, we compared 39,X(Y*)O MF1 mice to 40,XY MF1 mice on behavioural tasks taxing hippocampal and/or 5-HT function (a 'foraging' task, an object-location task, and the 1-choice serial reaction time task of impulsivity). Although Sts/Asmt deficiency did not influence foraging behaviour, reactivity to familiar objects in novel locations, or 'ability to wait', it did result in markedly increased response rates; these rates correlated with hippocampal 5-HT levels and are likely to index behavioural perseveration, a frequent feature of neurodevelopmental disorders. Additionally, we show that whilst there was no systematic relationship between serum DHEA levels and hippocampal 5-HT levels across 39,X(Y*)O and 40,XY mice, there was a significant inverse linear correlation between serum DHEA levels and activity. Our data suggest that deficiency for genes within Xp22.3 could influence core behavioural features of neurodevelopmental disorders via dissociable effects on hippocampal neurochemistry and steroid hormone levels, and that the mediating neurobiological mechanisms may be investigated in the 39,X(Y*)O model. Copyright © 2012 Elsevier Ltd. All rights reserved.

Altered plasma concentrations of sex hormones in cats infected by feline immunodeficiency virus or feline leukemia virus.

PubMed

Tejerizo, G; Doménech, A; Illera, J-C; Silván, G; Gómez-Lucía, E

2012-02-01

Gender differences may affect human immunodeficiency virus (HIV) infection in humans and may be related to fluctuations in sex hormone concentration. The different percentage of male and female cats observed to be infected by feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) has been traditionally explained through the transmission mechanisms of both viruses. However, sexual hormones may also play a role in this different distribution. To study this possibility, 17β-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) concentrations were analyzed using a competitive enzyme immunoassay in the plasma of 258 cats naturally infected by FIV (FIV(+)), FeLV (FeLV(+)), or FeLV and FIV (F(-)F(+)) or negative for both viruses, including both sick and clinically healthy animals. Results indicated that the concentrations of 17β-estradiol and testosterone were significantly higher in animals infected with FIV or FeLV (P < 0.05) than in negative cats. Plasma concentrations of DHEA in cats infected by either retrovirus were lower than in negative animals (P < 0.05), and F(-)F(+) cats had significantly lower plasma values than monoinfected cats (P < 0.05). No significant differences were detected in the plasma concentration of progesterone of the four groups. No relevant differences were detected in the hormone concentrations between animal genders, except that FIV(+) females had higher DHEA concentrations than the corresponding males (P < 0.05). In addition, no differences were observed in the hormone concentrations between retrovirus-infected and noninfected animals with and without clinical signs. These results suggest that FIV and FeLV infections are associated with an important deregulation of steroids, possibly from early in the infection process, which might have decisive consequences for disease progression. Copyright © 2012 Elsevier Inc. All rights reserved.

Dysfunctional stress responses in chronic pain.

PubMed

Woda, Alain; Picard, Pascale; Dutheil, Frédéric

2016-09-01

Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. Copyright © 2016 Elsevier Ltd. All rights reserved.

Equine fetal adrenal, gonadal and placental steroidogenesis.

PubMed

Legacki, Erin L; Ball, Barry A; Corbin, C Jo; Loux, Shavahn C; Scoggin, Kirsten E; Stanley, Scott D; Conley, Alan J

2017-10-01

Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA. Tissue steroid concentrations generally paralleled those in serum with time. Adrenal and gonadal tissue pregnenolone concentrations were similar and 100-fold higher than those in allantochorion. DHEA was far higher in gonads than adrenals and progesterone was higher in adrenals than gonads. Androstenedione decreased with GA in adrenals but not in gonads. Transcript analysis generally supported these data. CYP17A1 was higher in fetal gonads than adrenals or allantochorion, and HSD3B1 was higher in fetal adrenals and allantochorion than gonads. CYP11A1 transcript was also significantly higher in adrenals and gonads than allantochorion and CYP19 and SRD5A1 transcripts were higher in allantochorion than either fetal adrenals or gonads. Given these data, and their much greater size, the fetal gonads are the source of DHEA and likely contribute more than fetal adrenal glands to circulating fetal pregnenolone concentrations. Low CYP11A1 but high HSD3B1 and SRD5A1 transcript abundance in allantochorion, and low tissue pregnenolone, suggests that endogenous placental pregnenolone synthesis is low and likely contributes little to equine placental 5α-reduced pregnane secretion. © 2017 Society for Reproduction and Fertility.

Localization of the androgen-synthesizing enzymes, androgen receptor, and sex steroids in the vagina: possible implications for the treatment of postmenopausal sexual dysfunction.

PubMed

Bertin, Jonathan; Dury, Alain Y; Ouellet, Johanne; Pelletier, Georges; Labrie, Fernand

2014-08-01

To better understand the mechanisms underlying the beneficial effects of the intravaginal administration of dehydroepiandrosterone (DHEA) observed in postmenopausal women on sexual dysfunction. To identify the distribution of the androgen-synthesizing enzymes as well as androgen receptor (AR) and measure steroid levels in the monkey vagina. The cynomolgus monkey (Macaca fascicularis), the closest model to the human, has been used to measure the expression levels of steroidogenic enzymes and androgen receptor by quantitative reverse transcription polymerase chain reaction (n=4), confirmed by immunohistochemistry, and immunofluorescence (n=3). DHEA and its androgenic metabolites were quantified by LC-MS/MS (n=4). The presence of SRD5A1, SRD5A2, HSD17B3, AR as well as nerve fibers (PGP 9.5) was investigated, and steroid levels were measured. AR is widely distributed within the vaginal epithelium and also in the lamina propria with a lower expression in the muscularis layer and blood vessel walls. Androgen-forming enzymes, on the other hand, are expressed in the vaginal stratified squamous epithelium at a relatively high level where they are uniformly distributed from the basal membrane up to the superficial keratinized cells. The enzymes are at a lower level in blood vessel walls and zona muscularis where nerve fibers are localized. DHEA and its androgen metabolites are present at biologically significant concentrations in the monkey vagina. The enzymes responsible for androgen formation as well as AR are at the highest level in the superficial layer of the stratified epithelium and muscularis layers of the vagina. These data provide a potential explanation for the described role of androgens in regulating vaginal lubrication, smooth muscle activity, blood flow, and the neuronal activity potentially involved in the correction of sexual dysfunction. © 2014 International Society for Sexual Medicine.

Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS.

PubMed

Pizzo, Alfonsa; Laganà, Antonio Simone; Barbaro, Luisa

2014-03-01

Myo-inositol and D-chiro-inositol are capable of improving the ovarian function and metabolism of polycystic ovary syndrome (PCOS) patients. The aim of this work is to compare the effects of myo-inositol and D-chiro-inositol in PCOS. We enrolled 50 patients, with homogeneous bio-physical features, affected by PCOS and menstrual irregularities, and we randomly divided them into two groups: 25 were treated with 4 g of myo-inositol/die plus 400 mcg of folic acid/die orally for six months, 25 with 1 g of D-chiro-inositol/die plus 400 mcg of folic acid/die orally for six months. We analyzed in both groups pre-treatment and post-treatment BMI, systolic and diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), Δ-4-androstenedione, SHBG, prolactin, glucose/immunoreactive insulin (IRI) ratio, homeostatic model assessment (HOMA) index, and the resumption of regular menstrual cycles. Both the isoforms of inositol were effective in improving ovarian function and metabolism in patients with PCOS, although myo-inositol showed the most marked effect on the metabolic profile, whereas D-chiro-inositol reduced hyperandrogenism better.

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

PubMed

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

2016-09-20

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

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

PubMed Central

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

2016-01-01

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

Anabolic hormone profiles in elite military men.

PubMed

Taylor, Marcus K; Kviatkovsky, Shiloah A; Hernández, Lisa M; Sargent, Paul; Segal, Sabrina; Granger, Douglas A

2016-06-01

We recently characterized the awakening responses and daily profiles of the catabolic stress hormone cortisol in elite military men. Anabolic hormones follow a similar daily pattern and may counteract the catabolic effects of cortisol. This companion report is the first to characterize daily profiles of anabolic hormones dehydroepiandrosterone (DHEA) and testosterone in this population. Overall, the men in this study displayed anabolic hormone profiles comparable to that of healthy, athletic populations. Consistent with the cortisol findings in our prior report, summary parameters of magnitude (hormone output) within the first hour after awakening displayed superior stability versus summary parameters of pattern for both DHEA (r range: 0.77-0.82) and testosterone (r range: 0.62-0.69). Summary parameters of evening function were stable for the two hormones (both p<0.001), while the absolute decrease in testosterone across the day was a stable proxy of diurnal function (p<0.001). Removal of noncompliant subjects did not appreciably affect concentration estimates for either hormone at any time point, nor did it alter the repeatability of any summary parameter. The first of its kind, this report enables accurate estimations of anabolic balance and resultant effects upon health and human performance in this highly resilient yet chronically stressed population. Published by Elsevier Inc.

Altered adrenal steroid metabolism underlying hypercortisolism in female endurance athletes.

PubMed

Lindholm, C; Hirschberg, A L; Carlström, K; von Schoultz, B

1995-06-01

To explore possible changes in adrenal steroid metabolism and androgenic-anabolic status in female endurance athletes as a mechanism for their hypercortisolism. Adrenal steroids and androgenic-anabolic factors were studied during basal conditions and in response to ACTH stimulation related to menstrual status. Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden. Thirteen female elite middle to long distance runners (six eumenorrheic, seven oligoamenorrheic) and seven regularly menstruating controls. Blood samples were collected before and after an injection of 250 micrograms IV synthetic ACTH 1-24. Body weight, height, and body fat were measured. Basal serum concentrations of cortisol, androstenedione (A), DHEA, DHEAS, 17 alpha-hydroxyprogesterone (17-OHP), T, steroid-binding proteins, and insulin-like growth factor I and ACTH-induced response (area under the curve) of cortisol, DHEA, and 17-OHP. Oligoamenorrheic athletes had higher basal cortisol and A concentrations compared with healthy controls, whereas basal levels of DHEA and DHEAS were normal. Important findings in the oligoamenorrheic athletes were a significantly lower ratio between the ACTH-induced increments of DHEA and 17-OHP and an increased ratio between basal A and DHEAS. Insulin-like growth factor I was correlated negatively to sex hormone-binding globulin and to the amount of body fat in the combined material. The results indicate a redistribution of adrenal steroid metabolism in favor of glucocorticoid production in female endurance athletes. We suggest that hypercortisolism in female endurance athletes is a physiological adaptation to maintain adequate blood glucose levels during a condition of energy deficiency.

Steroidogenic alterations and adrenal androgen excess in PCOS.

PubMed

Doi, Suhail A R; Al-Zaid, Mona; Towers, Philip A; Scott, Christopher J; Al-Shoumer, Kamal A S

2006-09-01

This cross-sectional study was undertaken to improve our understanding of the steroidogenic alterations leading to adrenal hyperandrogenism in polycystic ovarian syndrome (PCOS). Two-hundred and thirty-four women with clinical and biochemical features suggestive of PCOS underwent metabolic and hormonal evaluation. We used the androstenedione/DHEAS ratio as a surrogate for the level of ovarian 3betaHSD activity. We then selected the 90th percentile for the ratio in those with elevated DHEAS (>9 micromol/l) as the cut-off level beyond which excess DHEAS production will be minimized by excess ovarian 3betaHSD activity. This cut-off level was at a ratio of 1.5 and all PCOS women were then divided into two groups, the higher (>1.5) being the group with excess ovarian 3betaHSD activity. We hypothesized that women with a high ratio would be unlikely to have DHEAS excess due to the rapid conversion of DHEA to androstenedione. Those with a low ratio (concordant ovarian and adrenal steroidogenesis) could then either have high DHEAS or normal DHEAS, depending on whether CYP17 activity was higher or lower respectively. Insulin resistance was found to be associated with decreased CYP17 activity while irregular cycles and neuroendocrine dysfunction were determined to be associated with higher ovarian 3betaHSD activity. Adrenal androgen excess in PCOS seems to be related to insulin sensitivity as well as decreased activity of 3betaHSD, the latter being preferentially present in those women with regular cycles or without neuroendocrine dysfunction.

Modulation of steroidogenesis by vitamin D3 in granulosa cells of the mouse model of polycystic ovarian syndrome.

PubMed

Bakhshalizadeh, Shabnam; Amidi, Fardin; Alleyassin, Ashraf; Soleimani, Masoud; Shirazi, Reza; Shabani Nashtaei, Maryam

2017-06-01

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women of reproductive age characterized by polycystic ovarian morphology, anovulation or oligomenorrhea, and hyperandrogenism. It is shown that disruption in the steroidogenesis pathway caused by excess androgen in PCOS is a critical element of abnormal folliculogenesis and failure in dominant follicle selection. Vitamin D plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells. In the present study, we investigated the effects of vitamin D3 on steroidogenic enzyme expression and activities in granulosa cell using a PCOS mouse model. In our study, the PCOS mouse model was developed by the injection of dehydroepiandrosterone (DHEA) for 20 days. The mRNA and protein expression levels of genes involved in steroidogenesis in granulosa cells were compared between polycystic and normal ovaries using real-time PCR and Western blotting assays. Granulosa cells of DHEA-induced PCOS mice were then cultured with and without vitamin D3 and mRNA and protein expression levels of steroidogenic enzymes and serum 17beta-estradiol and progesterone levels were investigated using qRT-PCR, western blot, and radioimmunoassay, respectively. Steroidogenic enzymes including Cyp11a1, StAR, Cyp19a1, and 3β-HSD were upregulated in granulosa cells of PCOS mice when compared to normal mice. Treatment with vitamin D3 decreased mRNA and protein expression levels of steroidogenic enzymes in cultured granulosa cells. Vitamin D3 also decreased aromatase and 3β-HSD activity that leads to decreased 17beta-estradiol and progesterone release. This study suggests that vitamin D3 could modulate the steroidogenesis pathway in granulosa cells of PCOS mice that may lead to improving follicular development and maturation. This is a step towards a possible conceivable treatment for PCOS. AMHR-II: anti-müllerian hormone receptor-II; 3β-HSD: 3�

Steroid profiles in serum by liquid chromatography-tandem mass spectrometry in infants with genital hair.

PubMed

Kaplowitz, Paul; Soldin, Steven J

2007-05-01

In recent years, an increasing number of infants have been seen with fine hair in the genital area and no other signs of androgen excess, but the hormonal basis of this finding is unknown. To compare steroid profiles in infants with genital hair with age-matched control infants, using liquid chromatography-tandem mass spectrometry (LC-TMS) to measure eight steroids (cortisol, 11-deoxycortisol, progesterone, 17-hydroxyprogesterone, testosterone, androstenedione, DHEA, and DHEA-S). Samples were obtained between 1/04 and 12/05 from infants with genital hair, and for comparison, a group of 5-9 year-olds with premature adrenarche, as well as control children of similar ages being seen for thyroid problems or short stature. Steroid profiles in infants with genital hair were similar to those in control infants, except that DHEA-S levels were somewhat higher (17.5 vs. 7.6 microg/dl [476 vs. 207 nmol/l]; p = 0.067), and six of 12 had levels >15 microg/dl (408 nmol/l) vs. one of 12 controls. Testosterone levels were low (<10 ng/dl [<350 pmol/l) in nearly all infants with pubic hair; the main exception was a girl whose father used topical testosterone (31 ng/dl [1076 pmol/l]). Genital hair disappeared in two patients over time but persisted for 6 months to 2 years in most. No pathological increase in steroid levels was found in infants with genital hair vs controls, though a mild elevation of DHEA-S was seen in about half. This suggests that pubic hair in infancy may represent a mild and early onset variant of premature adrenarche, with a benign clinical course.

SLCO2B1 and SLCO1B3 as New Targets for Enhancing Androgen Deprivation Therapy for Prostate Cancer

DTIC Science & Technology

2015-10-01

that statins block DHEAS uptake by competitively binding to SLCO2B1. We examined the effect of four different statins ( atorvastatin , fluvastatin...300 pmol/mg compared to ~60 pmol/mg protein for LNCaP (Fig. 2B). 100 µM atorvastatin significantly decreased DHEAS influx by ~50% in both cell...or even 100 µM atorvastatin or simvastatin was insufficient to inhibit DHEAS uptake in LNCaP, which has a relatively low level of SLCO2B1 expression

Steroid hormone levels associated with passive and active smoking

PubMed Central

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

2013-01-01

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

A New Parasiticidal Compound in T. solium Cysticercosis

PubMed Central

Hernández-Bello, Romel; Escobedo, Galileo; Carrero, Julio Cesar; Cervantes-Rebolledo, Claudia; Dowding, Charles; Frincke, James; Reading, Chris; Morales-Montor, Jorge

2013-01-01

The effect of 16α-bromoepiandrosterone (EpiBr), a dehydroepiandrosterone (DHEA) analogue, was tested on the cysticerci of Taenia solium, both in vitro and in vivo. In vitro treatment of T. solium cultures with EpiBr reduced scolex evagination, growth, motility, and viability in dose- and time-dependent fashions. Administration of EpiBr prior to infection with T. solium cysticerci in hamsters reduced the number and size of developed taenias in the intestine, compared with controls. These effects were associated to an increase in splenocyte proliferation in infected hamsters. These results leave open the possibility of assessing the potential of this hormonal analogue as a possible antiparasite drug, particularly in cysticercosis and taeniosis. PMID:23509732

The concept of multiple hormonal dysregulation.

PubMed

Maggio, Marcello; Cattabiani, Chiara; Lauretani, Fulvio; Ferrucci, Luigi; Luci, Michele; Valenti, Giorgio; Ceda, Gianpaolo

2010-01-01

Aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones that remain stable and anabolic hormones (testosterone, insulin like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with age. Despite the multiple hormonal dysregulation occurring with age, the prevalent line of research in the last decades has tried to explain many age-related phenomena as consequence of one single hormonal derangement with disappointing results. In this review we will list the relationship between hormonal anabolic deficiency and frailty and mortality in older population, providing evidence to the notion that multiple hormonal dysregulation rather than change in single anabolic hormone is a powerful marker of poor health status and mortality.

Efficacy of Chinese patent medicine Tian Gui Capsule in patients with polycystic ovary syndrome: a randomized controlled trial.

PubMed

Kuek, Susuana; Wang, Wen-jun; Gui, Sui-qi

2011-09-01

Polycystic ovary syndrome (PCOS) is a complex hormonal disorder and one of the most common reproductive endocrinology abnormalities in women. Recently, many studies have been conducted assessing Chinese herbal medicine as an alternative treatment for women with PCOS, it is, therefore, worthwhile to analyze and observe the curative effects of traditional Chinese medicine treatment in PCOS. To evaluate the efficacy of the Chinese patent medicine Tian Gui Capsule, in women with PCOS and compare its effects with metformin and ethinyl estradiol plus cyproterone acetate (Diane-35). A total of 47 PCOS outpatients from the Obstetrics and Gynecology Hospital of Fudan University were randomly divided into 3 groups. Patients in group A (n=19) were given Tian Gui Capsule, patients in group B (n=17) were given metformin, and patients in group C (n=11) were given Diane-35. The 3 groups of patients were treated for 3 months. Serum testosterone (T), sex hormone binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEA-S) levels, free androgen index (FAI), fasting blood glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitive index (ISI) and left and right ovary volumes of the 3 groups were evaluated before and after treatment . After 3 months of treatment, when compared with before treatment data, group A patients showed decreased serum T and SHBG levels, FAI, FINS, and left and right ovary volumes (P<0.05), and increased serum DHEA-S (P<0.05), while the FPG level showed no significant change. Although the level of serum T and FINS among the 3 groups after the treatment were similar, group A demonstrated better results than group B in reducing the FAI and increasing the serum SHBG, but less significant results than group C besides, group B was the only group showed improved insulin sensitivity. Although the level of FPG of the 3 groups after treatment were similar, group C had the most increased FPG. The effects

Altered metabolic homeostasis is associated with appetite regulation during and following 48-h of severe energy deprivation in adults.

PubMed

Karl, J Philip; Smith, Tracey J; Wilson, Marques A; Bukhari, Asma S; Pasiakos, Stefan M; McClung, Holly L; McClung, James P; Lieberman, Harris R

2016-04-01

Military personnel frequently endure intermittent periods of severe energy deficit which can compromise health and performance. Physiologic factors contributing to underconsumption, and the subsequent drive to overeat, are not fully characterized. This study aimed to identify associations between appetite, metabolic homeostasis and endocrine responses during and following severe, short-term energy deprivation. Twenty-three young adults (17M/6F, 21±3years, BMI 25±3kg/m(2)) participated in a randomized, controlled, crossover trial. During separate 48-h periods, participants increased habitual energy expenditure by 1647±345kcal/d (mean±SD) through prescribed exercise at 40-65% VO2peak, and consumed provided isovolumetric diets designed to maintain energy balance at the elevated energy expenditure (EB; 36±93kcal/d energy deficit) or to produce a severe energy deficit (ED; 3681±716kcal/d energy deficit). Appetite, markers of metabolic homeostasis and endocrine mediators of appetite and substrate availability were periodically measured. Ad libitum energy intake was measured over 36h following both experimental periods. Appetite increased during ED and was greater than during EB despite maintenance of diet volume (P=0.004). Ad libitum energy intake was 907kcal/36h [95% CI: 321, 1493kcal/36h, P=0.004] higher following ED compared to following EB. Serum beta-hydroxybutyrate, free fatty acids, branched-chain amino acids, dehydroepiandrosterone-sulfate (DHEA-S) and cortisol concentrations were higher (P<0.001 for all), whereas whole-body protein balance was more negative (P<0.001), and serum glucose, insulin, and leptin concentrations were lower (P<0.001 for all) during ED relative to during EB. Cortisol concentrations, but not any other hormone or metabolic substrate, were inversely associated with satiety during EB (R(2)=0.23, P=0.04). In contrast, serum glucose and DHEA-S concentrations were inversely associated with satiety during ED (R(2)=0.68, P<0.001). No

Predictors of severity of acne vulgaris in young adolescent girls: results of a five-year longitudinal study.

PubMed

Lucky, A W; Biro, F M; Simbartl, L A; Morrison, J A; Sorg, N W

1997-01-01

The objectives of this study were to determine which factors in early pubertal girls might be predictive of later, severe facial acne. The study was a 5-year longitudinal cohort study, with yearly visits from 1987 through 1991, in a volunteer sample of 439 black and 432 white fourth- and fifth-grade girls with consent from their legal guardians. The subjects were recruited from public and parochial schools in Cincinnati, Ohio. The degree of facial acne was classified annually as mild, moderate, or severe. Blood samples were obtained at the first, third, and fifth years of the study. Using the acne status during the fifth year of the study as the outcome variable, we determined the contributions from the prior acne status and the serum levels of dehydroepiandrosterone sulfate (DHEAS), testosterone, free testosterone (FT), estradiol (E2), progesterone, and testosterone-estrogen binding globulin (TEBG) and compared the results at various ages and at times before and after menarche. No racial differences in acne or hormone levels were found. There was a progressive increase in the number of acne lesions with age and maturation. The girls exhibited many more comedonal than inflammatory acne lesions, regardless of age. The girls in whom severe acne developed by the fifth year of the study had significantly more comedones and inflammatory lesions than girls with mild or moderate acne, as early as age 10 years, approximately 2 h years before menarche, a time when their degree of acne was mild. Girls with mild comedonal acne had significantly later onset of menarche (12.5 compared with 12.2 years) than girls with severe comedonal acne. Girls in whom severe comedonal acne developed had significantly higher levels of serum DHEAS and, in a longitudinal analysis, somewhat higher levels of testosterone and FT in comparison with girls who had mild or moderate comedonal acne. Serum E2, testosterone/E2, progesterone, and TEBG values were no different in girls with severe compared

Differentiating Medicated Patients Suffering from Major Depressive Disorder from Healthy Controls by Spot Urine Measurement of Monoamines and Steroid Hormones

PubMed Central

Wijaya, Chandra S.; Lee, Jovia J. Z.; Husain, Syeda F.; Ho, Cyrus S. H.; McIntyre, Roger S.; Tam, Wilson W.

2018-01-01

Introduction: Major Depressive Disorder (MDD) is a common psychiatric disorder. Currently, there is no objective, cost-effective and non-invasive method to measure biological markers related to the pathogenesis of MDD. Previous studies primarily focused on urinary metabolite markers which are not proximal to the pathogenesis of MDD. Herein, we compare urinary monoamines, steroid hormones and the derived ratios amongst MDD when compared to healthy controls. Methods: Morning urine samples of medicated patients suffering from MDD (n = 47) and healthy controls (n = 41) were collected. Enzyme-linked immunosorbent assay (ELISA) was performed to measure five biomarkers: cortisol, dopamine, noradrenaline, serotonin and sulphate derivative of dehydroepiandrosterone (DHEAS). The mean urinary levels and derived ratios of monoamines and steroid hormones were compared between patients and controls to identify potential biomarkers. The receiver operative characteristic curve (ROC) analysis was conducted to evaluate the diagnostic performance of potential biomarkers. Results: Medicated patients with MDD showed significantly higher spot urine ratio of DHEAS/serotonin (1.56 vs. 1.19, p = 0.004) and lower ratio of serotonin/dopamine (599.71 vs. 888.60, p = 0.008) than healthy controls. A spot urine serotonin/dopamine ratio cut-off of >667.38 had a sensitivity of 73.2% and specificity of 51.1%. Conclusions: Our results suggest that spot urine serotonin/dopamine ratio can be used as an objective diagnostic method for adults with MDD. PMID:29701669

Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients

PubMed Central

Corrêa, Márcio Silveira; Giacobbo, Bruno Lima; Vedovelli, Kelem; de Lima, Daiane Borba; Ferrari, Pamela; Argimon, Irani Iracema de Lima; Walz, Julio Cesar

2016-01-01

Objectives Older familial caregivers of Alzheimer’s disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. Method The cognitive measures of 17 young (31–58 years) and 18 old (63–84 years) caregivers and of 17 young (37–57 years) and 18 old (62–84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Results Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Discussion Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions. PMID:27706235

Effect of oral contraceptives on markers of hyperandrogenism and SHBG in women with polycystic ovary syndrome.

PubMed

De Leo, Vincenzo; Di Sabatino, Alessandra; Musacchio, Maria C; Morgante, Giuseppe; Scolaro, Valeria; Cianci, Antonio; Petraglia, Felice

2010-09-01

This randomized study's aim was to compare the effect of four oral contraceptives (OCs) containing 30 mcg of ethinylestradiol (EE) and different progestogens [drospirenone, (DRSP), chlormadinone acetate (CMA), desogestrel (DSG), gestodene (GSD)] on biochemical and hormonal parameters of hyperandrogenism and sex hormone-binding globulin (SHBG) in women with polycystic ovary syndrome (PCOS). Forty women with PCOS (age 16-35 years) were recruited and randomly assigned to one of four treatment groups of 10 women each, treated, respectively, with 3 mg DRSP/30 mcg EE (Yasmin, Bayer Shering), 2 mg CMA/30 mcg EE (Belara, Grunenthal), 75 mcg GSD/30 mcg EE (Minulet, Wyeth Lederle) and 150 mcg DSG/30 mcg EE (Practil 21, Organon Italia). Blood samples were obtained on day 6-8 of the control cycle and day 6-8 of the third treatment cycle for assay of the following hormones: androsteredione (A), total testosterone (T), free T, SHBG, dehydroepiandrosterone sulphate (DHEAS). In all groups, mean concentrations of free T, total T and A dropped by 40-60%, and concentrations of DHEAS dropped by 20-50%. Formulations with DRSP and CMA caused a greater reduction of androgens and a progressive increase in serum concentrations of SHBG than those with DSG and GSD. Clinical studies need to be performed to determine effects of these OCs upon clinical signs of hyperandrogenism. Copyright 2010 Elsevier Inc. All rights reserved.

Pregnancy, the postpartum, and steroid hormones: effects on cognition and mood.

PubMed

Buckwalter, J G; Stanczyk, F Z; McCleary, C A; Bluestein, B W; Buckwalter, D K; Rankin, K P; Chang, L; Goodwin, T M

1999-01-01

The effects of pregnancy on cognition and mood were examined using a repeated-measures design. Nineteen women, average age 33, were tested with a comprehensive neuropsychological battery during their last 2 months of pregnancy and again within 2 months of delivery. Blood samples were obtained from all subjects and assayed for a variety of steroid hormones implicated in cognitive and mood functioning. Most participants also completed several self-report measures of mood. In comparison with performance after delivery, women showed significantly more impairment in aspects of verbal memory during pregnancy and also tended to report more negative mood states. Memory deficits were not explained by mood disturbances. No hormone assayed consistently related to cognitive performance during pregnancy. During pregnancy, higher levels of progesterone (P) were associated with greater mood disturbances and higher levels of dehydroepiandrosterone (DHEA) with better mood. After delivery, testosterone (T) was strongly and consistently associated with greater reported mood disturbances. Our results confirm a peripartal memory deficit, which cannot be explained by the dramatic rise in circulating steroid hormones, or by mood status during pregnancy. Steroidal hormones, namely P, DHEA and T, appear to play a role in mood disturbances during, and after, pregnancy. Studies beginning earlier in pregnancy and continuing for an extended period of time after delivery are needed to confirm and expand these observations.

Chemoprevention of hormone-dependent prostate cancer in the Wistar-Unilever rat.

PubMed

McCormick, D L; Rao, K V

1999-01-01

The high incidence and long latent period of prostate cancer make it an ideal target for chemoprevention. We have evaluated a series of agents for chemopreventive efficacy using a model in which hormone-dependent prostate cancers are induced in the Wistar-Unilever (WU) rat by sequential treatment with antiandrogen (cyproterone acetate), androgen (testosterone propionate), and direct-acting chemical carcinogen (N-methyl-N-nitrosourea), followed by chronic androgen stimulation (testosterone). This regimen reproducibly induces prostate cancers in high incidence, with no gross toxicity and a low incidence of neoplasia in the seminal vesicle and other non-target tissues. Dehydroepiandrosterone (DHEA) and 9-cis-retinoic acid (9-cis-RA) are the most active agents identified to date. DHEA inhibits prostate cancer induction both when chronic administration is begun prior to carcinogen exposure, and when administration is delayed until preneoplastic prostate lesions are present. 9-cis-RA is the most potent inhibitor of prostate carcinogenesis identified; a study to determine the efficacy of delayed administration of 9-cis-RA is in progress. Liarozole fumarate confers modest protection against prostate carcinogenesis, while N-(4-hydroxyphenyl)retinamide (fenretinide), alpha-difluoromethylornithine, oltipraz, DL-alpha-tocopherol acetate (vitamin E), and L-selenomethionine are inactive. Chemoprevention efficacy evaluations in the WU rat will support the identification of agents that merit study for prostate cancer chemoprevention in humans.

Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone.

PubMed

Bosch, Oliver G; Eisenegger, Christoph; Gertsch, Jürg; von Rotz, Robin; Dornbierer, Dario; Gachet, M Salomé; Heinrichs, Markus; Wetter, Thomas C; Seifritz, Erich; Quednow, Boris B

2015-12-01

Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analogue-scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic-hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected. GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABAB-receptors and progesterone in mood and prosocial behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss.

PubMed

Reinehr, Thomas; Kulle, Alexandra; Rothermel, Juliane; Knop-Schmenn, Caroline; Lass, Nina; Bosse, Christina; Holterhus, Paul-Martin

2017-05-01

The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13-16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC-MS/MS steroid profiling at baseline and one year later. At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS. © 2017 The authors.

Gender and Gonadal Status Differences in Zona Reticularis Expression in Marmoset Monkey Adrenals: Cytochrome b5 Localization With Respect To Cytochrome P450 17,20-Lyase Activity.

PubMed Central

Pattison, J Christina; Saltzman, Wendy; Abbott, David H; Hogan, Brynn K; Nguyen, Ann D; Husen, Bettina; Einspanier, Almuth; Conley, Alan J; Bird., Ian M

2007-01-01

Neonatal marmosets express an adrenal fetal zone comparable to humans. While adult males fail to express a functional ZR, with barely detectable blood DHEA levels, females produce higher levels of DHEA than males in adulthood. We investigated the presence of a putative functional ZR in adult female marmosets. In contrast to males, immunohistochemical analysis showed the ZR marker cytochrome b5 was elevated in the innermost zone in cycling females (compared to testis-intact males), further elevated in the adrenals from anovulatory females, and substantially elevated and continuous in ovariectomized females. As a functional test in vivo, following overnight dexamethasone treatment, cycling and anovulatory females showed higher levels of DHEA relative to males, but DHEA failed to increase in response to ACTH. In direct contrast, while ovariectomized females exhibited lower initial DHEA levels, clear increases were detectable after ACTH administration (p<0.05), suggesting an adrenal origin. The apparent differences in cytochrome b5 expression between groups were also further verified by western blotting of adrenal microsomes, and compared to 17,20-lyase activity; the two parameters were positively correlated (p<0.01) across multiple treatment groups. We conclude that the cycling female marmoset expresses a rudimentary ZR with at least a capacity for DHEA production that becomes significantly ACTH-responsive after anovulation. Expression of cytochrome b5 in this region may be directly or indirectly controlled by gonadal function, and is, at least in part, a critical determinant in the development of an adrenal ZR that is more defined and significantly ACTH-responsive. PMID:17222503

Impact of emotional disorders on semen quality in men treated for infertility.

PubMed

Wdowiak, Artur; Bień, Agnieszka; Iwanowicz-Palus, Grażyna; Makara-Studzińska, Marta; Bojar, Iwona

2017-02-01

Semen quality depends on factors such as lifestyle, environment, and hormone secretion. The purpose of the study was to assess the correlation between emotional disorders and the secretion of selected hormones, and to assess the impact of these disorders on semen quality. The study covered 60 fertile and 112 subfertile males. The sperm was obtained by masturbation, and examined directly after liquidation according to the 2010 criteria of the World Health Organization. The research instruments used were: the Beck Depression Inventory (BDI), and the State-Trait Anxiety Inventory (STAI). A morning blood sample (5 mL volume) was obtained and sent to an authorized laboratory to assess serum levels of testosterone, LH, FSH, prolactin, SHBG, DHEA-S and cortisol. In the group of infertility patients, higher BDI scores were correlated with significantly decreased testosterone levels (p=0.001), and increased prolactin and cortisol (p<0.001); statistically significant negative correlations were also found between BDI score and SHBG and DHEA-S (p<0.001) levels. Higher STAI-1 and STAI-2 in the low-fertility group were associated with higher mean prolactin and cortisol levels (p<0.001). Sperm count was shown to be correlated with BDI, STAI-1 and STAI-2 scores (p<0.001). Semen volume also correlated with BDI, STAI-1 and STAI-2 scores (p<0.001). Depression and anxiety in subfertile males are associated with lower secretion of SHBG and DHEA-S, and higher secretion of cortisol and prolactin. Depression and anxiety in male patients cause decreased semen volume and sperm density.

Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women

PubMed Central

Nair, K. Sreekumaran; Daniels, Janice K.; Basal, Eati; Schimke, Jill M.

2012-01-01

Hyperandrogenism and chronic low-grade inflammation are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate inflammation. We determined the effect of oral androgen administration on fasting and glucose-stimulated nuclear factor-κB (NF-κB) activation and expression and related markers of inflammation in mononuclear cells (MNC) of lean reproductive-age women. Sixteen lean, ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n = 8 each) for 5 days in a randomized, controlled, double-blind fashion. Nuclear activation of NF-κB, p65 and p105 NF-κB subunit RNA, TNFα and IL-1β mRNA, and NF-κB p65 and inhibitory-κB (IκB) protein were quantified from MNC obtained while fasting and 2 h after glucose ingestion, before and after DHEA or placebo administration. Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any inflammatory markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-S, increased the percent change in fasting and glucose-challenged activated NF-κB, p65, p105, TNFα, and IL-1β RNA and p65 protein, and decreased the percent change in fasting and glucose-challenged IκB protein. We conclude that elevation of circulating androgens to the range observed in PCOS upregulates the NF-κB inflammation pathway in lean reproductive-age women. Thus, hyperandrogenemia activates and sensitizes MNC to glucose in this population. PMID:22045316

Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women.

PubMed

González, Frank; Nair, K Sreekumaran; Daniels, Janice K; Basal, Eati; Schimke, Jill M

2012-02-01

Hyperandrogenism and chronic low-grade inflammation are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate inflammation. We determined the effect of oral androgen administration on fasting and glucose-stimulated nuclear factor-κB (NF-κB) activation and expression and related markers of inflammation in mononuclear cells (MNC) of lean reproductive-age women. Sixteen lean, ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n = 8 each) for 5 days in a randomized, controlled, double-blind fashion. Nuclear activation of NF-κB, p65 and p105 NF-κB subunit RNA, TNFα and IL-1β mRNA, and NF-κB p65 and inhibitory-κB (IκB) protein were quantified from MNC obtained while fasting and 2 h after glucose ingestion, before and after DHEA or placebo administration. Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any inflammatory markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-S, increased the percent change in fasting and glucose-challenged activated NF-κB, p65, p105, TNFα, and IL-1β RNA and p65 protein, and decreased the percent change in fasting and glucose-challenged IκB protein. We conclude that elevation of circulating androgens to the range observed in PCOS upregulates the NF-κB inflammation pathway in lean reproductive-age women. Thus, hyperandrogenemia activates and sensitizes MNC to glucose in this population.

Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Zhao, Di; Ouyang, Pamela; de Boer, Ian H; Lutsey, Pamela L; Farag, Youssef M K; Guallar, Eliseo; Siscovick, David S; Post, Wendy S; Kalyani, Rita R; Billups, Kevin L; Michos, Erin D

2017-02-01

25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low testosterone levels in men, but there are conflicting reports of its associations with sex hormones in women. Less is known about whether these associations are independent of adiposity and lifestyle factors, and whether they differ by race/ethnicity. To examine associations of 25(OH)D concentrations with sex hormone levels. Cross-sectional analysis of 3017 men and 2929 women in a multi-ethnic cohort. Testosterone, estradiol, dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and free testosterone. The mean (SD) levels of 25(OH)D in men and women were 25.7(10.4) and 26.1(12.0)ng/ml, respectively. In men, after adjusting for demographic and lifestyle variables, a 10ng/ml [25nmol/L] decrease in 25(OH)D was associated with an average difference of -0.70nmol/L (95%CI -1.36, -0.05) in SHBG and 0.02 percent (0.01, 0.04) in free testosterone, but was not associated with low total testosterone level (<10.41nmol/L). In women, a 10ng/ml decrease in 25(OH)D levels was associated with an average difference of -0.01nmol/L (-0.01, -0.00) for estradiol, -8.29nmol/L (-10.13, -6.45) for SHBG, 0.06 percent (0.04, 0.07) for free testosterone, and 0.40nmol/L (0.19, 0.62) for DHEA. There was no significant interaction by race/ethnicity. Lower 25(OH)D concentrations were associated with lower SHBG levels and higher free testosterone levels in both men and women, and lower estradiol and higher DHEA levels in women, independent of adiposity and lifestyle. We observed no significant association of 25(OH)D with total testosterone in men. Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Predictors of sexual desire disorders in women.

PubMed

Brotto, Lori A; Petkau, A John; Labrie, Fernand; Basson, Rosemary

2011-03-01

A historic belief was that testosterone was the "hormone of desire." However, recent data, which show either minimal or no significant correlation between testosterone levels and women's sexual desire, suggest that nonhormonal variables may play a key role. To compare women with hypoactive sexual desire disorder (HSDD) and those with the recently proposed more symptomatic desire disorder, Sexual Desire/Interest Disorder (SDID), on the relative contribution of hormonal vs. nonhormonal variables. Women with HSDD (N = 58, mean age 52.5) or SDID (N = 52, mean age 50.9) participated in a biopsychosocial assessment in which six nonhormonal domains were evaluated for the degree of involvement in the current low desire complaints. Participants provided a serum sample of hormones analyzed by gas chromatography-mass spectrometry or liquid chromatography/mass spectrometry/mass spectrometry. Logistic regression was used to assess the ability of variables (nonhormonal: history of sexual abuse, developmental history, psychosexual history, psychiatric status, medical history, and sexual/relationship-related factors; hormonal: dehydroepiandrosterone [DHEA], 5-diol, 4-dione, testosterone, 5-α-dihydrotestosterone, androsterone glucuronide, 3α-diol-3G, 3α-diol-17G, and DHEA-S; and demographic: age, relationship length) to predict group membership. Women with SDID had significantly lower sexual desire and arousal scores, but the groups did not differ on relationship satisfaction or mood. Addition of the hormonal variables to the two demographic variables (age, relationship length) did not significantly increase predictive capability. However, the addition of the six nonhormonal variables to these two sets of predictors significantly increased ability to predict group status. Developmental history, psychiatric history, and psychosexual history added significantly to the predictive capability provided by the basic model when examined individually. Nonhormonal variables added

GABA(A) receptor modulation during adolescence alters adult ethanol intake and preference in rats.

PubMed

Hulin, Mary W; Amato, Russell J; Winsauer, Peter J

2012-02-01

To address the hypothesis that GABA(A) receptor modulation during adolescence may alter the abuse liability of ethanol during adulthood, the effects of adolescent administration of both a positive and negative GABA(A) receptor modulator on adult alcohol intake and preference were assessed. Three groups of adolescent male rats received 12 injections of lorazepam (3.2 mg/kg), dehydroepiandrosterone (DHEA, 56 mg/kg), or vehicle on alternate days starting on postnatal day (PD) 35. After this time, the doses were increased to 5.6 and 100 mg/kg, respectively, for 3 more injections on alternate days. Subjects had access to 25 to 30 g of food daily, during the period of the first 6 injections, and 18 to 20 g thereafter. Food intake of each group was measured 60 minutes after food presentation, which occurred immediately after drug administration on injection days or at the same time of day on noninjection days. When subjects reached adulthood (PD 88), ethanol preference was determined on 2 separate occasions, an initial 3-day period and a 12-day period, in which increasing concentrations of ethanol were presented. During each preference test, intake of water, saccharin, and an ethanol/saccharin solution was measured after each 23-hour access period. During adolescence, lorazepam increased 60-minute food intake, and this effect was enhanced under the more restrictive feeding schedule. DHEA had the opposite effect on injection days, decreasing food intake compared with noninjection days. In adulthood, the lorazepam-treated group preferred the 2 lowest concentrations of ethanol/saccharin more than saccharin alone compared with vehicle-treated subjects, which showed no preference for any concentration of ethanol/saccharin over saccharin. DHEA-treated subjects showed no preference among the 3 solutions. These data demonstrate that GABA(A) receptor modulation during adolescence can alter intake and preference for ethanol in adulthood and highlights the importance of drug history

Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss

PubMed Central

Kulle, Alexandra; Rothermel, Juliane; Knop-Schmenn, Caroline; Lass, Nina; Bosse, Christina; Holterhus, Paul-Martin

2017-01-01

Objective The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. Design This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13–16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. Methods We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC–MS/MS steroid profiling at baseline and one year later. Results At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. Conclusions The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS. PMID:28373267

Effect of Diane-35, alone or in combination with orlistat or metformin in Chinese polycystic ovary syndrome patients.

PubMed

Ruan, Xiangyan; Song, Jinghua; Gu, Muqing; Wang, Lijuan; Wang, Husheng; Mueck, Alfred O

2018-06-01

To evaluate the effect of Diane-35, alone or in combination with orlistat or metformin, on androgen and body fat percentage parameters in Chinese overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance. A total of 240 PCOS women were randomly allocated to receive Diane-35 alone (D group), Diane-35 plus orlistat (DO group), Diane-35 plus metformin (DM group), or Diane-35 plus orlistat plus metformin (DOM group). Serum TT, DHEA-S, androstenedione, SHBG, FT, FAI, body fat, and body fat percentage were assessed at baseline and after 12 weeks of treatment. Significant changes in serum TT, SHBG, and FAI were observed in all treatment groups compared with baseline. DHEA-S and androstenedione significantly decreased in the DO, DM, and DOM groups after treatment. FT only significantly decreased in the DOM group. Body fat and body fat percentage significantly decreased in the DO and DOM groups. Compared with the D group, DHEA-S significantly decreased in the DO, DM, and DOM groups (F = 4.081, p = 0.008); SHBG significantly increased in the DOM group (F = 3.019, p = 0.031); and FAI significantly decreased in the DO group (χ 2  = 12.578, p = 0.006). There were significant differences between groups in body fat percentage (χ 2  = 23.590, p < 0.001). Side-effects were less with orlistat than metformin. Diane-35 in combination with orlistat or metformin is more effective in reducing androgen than Diane-35 alone. Orlistat is more effective in reducing body fat percentage than metformin. In addition, orlistat has mild side-effects and is better tolerated compared with metformin.

The concept of multiple hormonal dysregulation

PubMed Central

Maggio, Marcello; Cattabiani, Chiara; Lauretani, Fulvio; Ferrucci, Luigi; Luci, Michele; Valenti, Giorgio; Ceda, Gianpaolo

2016-01-01

Aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones that remain stable and anabolic hormones (testosterone, insulin like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with age. Despite the multiple hormonal dysregulation occurring with age, the prevalent line of research in the last decades has tried to explain many age-related phenomena as consequence of one single hormonal derangement with disappointing results. In this review we will list the relationship between hormonal anabolic deficiency and frailty and mortality in older population, providing evidence to the notion that multiple hormonal dysregulation rather than change in single anabolic hormone is a powerful marker of poor health status and mortality. (www.actabiomedica.it) PMID:20518188

Premature adrenarche: novel lessons from early onset androgen excess.

PubMed

Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

2011-08-01

Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

Fetal programming of adrenal androgen excess: lessons from a nonhuman primate model of polycystic ovary syndrome

PubMed Central

Abbott, David H; Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Conley, Alan J

2008-01-01

Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of DHEAS, typical of PCOS women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS. PMID:18493139

Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines

PubMed Central

Brown, Iain; Cascio, Maria G.; Wahle, Klaus W.J.; Smoum, Reem; Mechoulam, Raphael; Ross, Ruth A.; Pertwee, Roger G.; Heys, Steven D.

2010-01-01

The omega-3 fatty acid ethanolamides, docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA), displayed greater anti-proliferative potency than their parent omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in LNCaP and PC3 prostate cancer cells. DHEA and EPEA activated cannabinoid CB1 and CB2 receptors in vitro with significant potency, suggesting that they are endocannabinoids. Both LNCaP and PC3 cells expressed CB1 and CB2 receptors, and the CB1- and CB2-selective antagonists, AM281 and AM630, administered separately or together, reduced the anti-proliferative potencies of EPEA and EPA but not of DHEA or DHA in PC3 cells and of EPA but not of EPEA, DHEA or DHA in LNCaP cells. Even so, EPEA and EPA may not have inhibited PC3 or LNCaP cell proliferation via cannabinoid receptors since the anti-proliferative potency of EPEA was well below the potency it displayed as a CB1 or CB2 receptor agonist. Indeed, these receptors may mediate a protective effect because the anti-proliferative potency of DHEA in LNCaP and PC3 cells was increased by separate or combined administration of AM281 and AM630. The anandamide-metabolizing enzyme, fatty acid amide hydrolase (FAAH), was highly expressed in LNCaP but not PC3 cells. Evidence was obtained that FAAH metabolizes EPEA and DHEA and that the anti-proliferative potencies of these ethanolamides in LNCaP cells can be enhanced by inhibiting this enzyme. Our findings suggest that the expression of cannabinoid receptors and of FAAH in some tumour cells could well influence the effectiveness of DHA and EPA or their ethanolamide derivatives as anticancer agents. PMID:20660502

Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function.

PubMed

Altuntas, Yuksel; Bilir, Muammer; Ucak, Sema; Gundogdu, Sadi

2005-04-01

Reactive hypoglycemia (RH), which is a postprandial hypoglycemic state, occurs within 2-5 h after food intake. It is classified as idiopathic, alimentary, or diabetic reactive hypoglycemia. We studied the incidence of reactive hypoglycemia and looked for any correlations between it and the presence of insulin sensitivity and/or beta cell function in young lean polycystic ovary syndrome (PCOS) patients. This study was designed as a cross-sectional study in 64 lean young women with PCOS (BMI < or = 25 kg/m2). Various indices of insulin sensitivity and beta cell function derived from the oral glucose tolerance test (OGTT) results were used. We found the rate of RH to be 50% in lean young women with PCOS. DHEA-S and PRL levels were found to be lower in subjects with RH (P < 0.05 and P > 0.05, respectively). Beta cell function indices such as the insulinogenic index (at 120 min), CIR (at 120 min) and HOMA beta cell index were found to be insignificantly higher in the RH group than the nonreactive hypoglycemia (NRH) group. The 4 h glucose level, but not the 3 h glucose level, was significantly correlated with insulin resistance indices, such as fasting insulin level, HOMA-IR, Quicky index, and FIRI in the RH group. Significantly decreased DHEA-S levels were an interesting finding. In conclusion, there is an urgent need to investigate RH in lean young women with PCOS. Our results indicate that more definite insulin resistance occurs in subjects with RH in the fourth hour of the OGTT than those with RH in the third hour. In addition, RH in the fourth hour together with a low DHEA-S level may be predictive of future diabetes in young women with PCOS even when they are not obese.

Rat organic solute carrier protein 1 (rOscp1) mediated the transport of organic solutes in Xenopus laevis oocytes: isolation and pharmacological characterization of rOscp1.

PubMed

Izuno, Hisanori; Kobayashi, Yasuna; Sanada, Yutaka; Nihei, Daisuke; Suzuki, Masako; Kohyama, Noriko; Ohbayashi, Masayuki; Yamamoto, Toshinori

2007-09-22

Rat organic solute carrier protein 1 (rOscp1) was isolated from a rat testis cDNA library. Isolated rOscp1 cDNA consisted of 1089 base pairs that encoded a 363-amino acid protein, and the amino acid sequence was 88% and 93% identical to that of human OSCP1 (hOSCP1) and mouse Oscp1 (mOscp1), respectively. The message for rOscp1 is highly detected in rat testis. When expressed in X. oocytes, rOscp1 mediated the high affinity transport of p-aminohippurate (PAH) with a Km value of 15.7+/-1.9 microM, and rOscp1-mediated organic solutes were exhibited in time- and Na+-independent manners. rOscp1 also transported various structurally heterogenous compounds such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), and taurocholate with some differences in substrate specificity compared with hOSCP1. Immunohistochemical analysis revealed that the rOscp1 protein is localized in the basal membrane side of Sertoli cells as observed in mouse testis [Kobayashi et al., 2007; Kobayashi, Y., Tsuchiya, A., Hayashi, T., Kohyama, N., Ohbayashi, M., Yamamoto, T., 2007. Isolation and characterization of polyspecific mouse organic solute carrier protein 1 (mOscp1). Drug Metabolism and Disposition 35 (7), 1239-1245]. Thus, the present results indicate that a newly isolated cDNA clone, rOscp1, is a polyspecific organic solute carrier protein with some differences in substrate specificity compared with human and mouse OSCP1.

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

PubMed Central

Mostaghel, Elahe A

2014-01-01

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

Chronic work stress and exhaustion is associated with higher allostastic load in female school teachers.

PubMed

Bellingrath, Silja; Weigl, Tobias; Kudielka, Brigitte M

2009-01-01

Epidemiological studies have shown that chronic work stress or unfavourable psychosocial work conditions are prospectively associated with different adverse health outcomes. The aim of the present cross-sectional study was to investigate the relationship between work-related chronic stress as well as exhaustion and a cumulative measure of physiological wear-and-tear called allostastic load (AL). AL could be a possible biological pathway for how chronic work stress and exhaustion lead to health impairments in the long run. As the teaching profession has been proposed to be a potentially high stressful occupation, chronic work stress (effort-reward-imbalance) and exhaustion were assessed in 104 female school teachers. AL was first analyzed according to McEwen's classical model comprised of ten parameters including cortisol, epinephrine and norepinephrine, dehydroepiandrosterone-sulphate (DHEA-S), waist/hip-ratio (WHR), glycosylated haemoglobin (HbA1c), high-density lipoprotein (HDL), total cholesterol/HDL-ratio, and systolic and diastolic blood pressure. Additionally it was extended to include tumor-necrosis-factor-alpha (TNF-alpha), C-reactive protein (CRP), fibrinogen, D-dimer, percent-body-fat, triglycerides, and glucose levels. A substantial proportion of our sample was highly exhausted whereas relatively few teachers showed high effort-reward-imbalance. AL scores were significantly higher in women high on effort-reward-imbalance or suffering from exhaustion. Although all teachers had been in a good health status, chronic work stress as well as exhaustion appears to be associated with changes in a multi-system summary indicator of physiological risk.

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.

GPR30 Gene Polymorphisms Are Associated with Gynecomastia Risk in Adolescents.

PubMed

Korkmaz, Hüseyin Anıl; Edgünlü, Tuba; Eren, Erdal; Demir, Korcan; Çakir, Esra Deniz Papatya; Çelik, Sevim Karakaș; Özkan, Behzat

2015-01-01

The G protein-coupled receptor, GPR30, which is a third estrogen receptor, has been shown to mediate estrogenic effects on the essential features of human breast cancer cells. The aim of this study was to evaluate the association between GPR30 single nucleotide polymorphisms and gynecomastia in males. This study included 109 male adolescents with gynecomastia and 104 controls. Follicle stimulating hormone, luteinizing hormone, total testosterone, estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and prolactin levels were measured. DNA was extracted from whole blood using a GeneJET Genomic DNA purification kit. The genotypes of the GPR30 gene (rs3808350, rs3808351 and rs11544331) were studied using a tetra-primer ARMS (amplification refractory mutation system) PCR approach. The median E2 (11.80 vs. 16.86 IU/l, p < 0.001) and DHEAS levels (116.8 vs. 146.5 μg/dl, p = 0.044) were higher in the gynecomastia group. The G allele of rs3808350 and the A allele of rs3808351 were frequently observed in patients with gynecomastia. Gynecomastia was more common in patients with the GG genotype of rs3808350 and in patients with the AA genotype of rs3808351. Our results suggest that increased E2 levels, the G allele of rs3808350 and the A allele of rs3808351 might explain why certain adolescents are affected by gynecomastia. © 2014 S. Karger AG, Basel.

Potential neurobiological benefits of exercise in chronic pain and posttraumatic stress disorder: Pilot study.

PubMed

Scioli-Salter, Erica; Forman, Daniel E; Otis, John D; Tun, Carlos; Allsup, Kelly; Marx, Christine E; Hauger, Richard L; Shipherd, Jillian C; Higgins, Diana; Tyzik, Anna; Rasmusson, Ann M

2016-01-01

This pilot study assessed the effects of cardiopulmonary exercise testing and cardiorespiratory fitness on plasma neuropeptide Y (NPY), allopregnanolone and pregnanolone (ALLO), cortisol, and dehydroepiandrosterone (DHEA), and their association with pain sensitivity. Medication-free trauma-exposed participants were either healthy (n = 7) or experiencing comorbid chronic pain/posttraumatic stress disorder (PTSD) (n = 5). Peak oxygen consumption (VO2) during exercise testing was used to characterize cardiorespiratory fitness. Peak VO2 correlated with baseline and peak NPY levels (r = 0.66, p < 0.05 and r = 0.69, p < 0.05, respectively), as well as exercise-induced changes in ALLO (r = 0.89, p < 0.001) and peak ALLO levels (r = 0.71, p < 0.01). NPY levels at the peak of exercise correlated with pain threshold 30 min after exercise (r = 0.65, p < 0.05), while exercise-induced increases in ALLO correlated with pain tolerance 30 min after exercise (r = 0.64, p < 0.05). In contrast, exercise-induced changes in cortisol and DHEA levels were inversely correlated with pain tolerance after exercise (r = -0.69, p < 0.05 and r = -0.58, p < 0.05, respectively). These data suggest that cardiorespiratory fitness is associated with higher plasma NPY levels and increased ALLO responses to exercise, which in turn relate to pain sensitivity. Future work will examine whether progressive exercise training increases cardiorespiratory fitness in association with increases in NPY and ALLO and reductions in pain sensitivity in chronic pain patients with PTSD.

The role of GABA-A and mitochondrial diazepam-binding inhibitor receptors on the effects of neurosteroids on food intake in mice.

PubMed

Reddy, D S; Kulkarni, S K

1998-06-01

The present studies were undertaken to investigate the neuroactive steroidal modulation of feeding behavior and possible involvement of gamma-aminobutyric acid type-A (GABA-A) and mitochondrial diazepam binding inhibitor (DBI) receptors (MDR) in food-deprived male mice. Allopregnanolone (0.5-2 mg/kg), a neurosteroid, progesterone (1-10 mg/kg), a neurosteroid precursor, and 4'-chlordiazepam (0.25-1 mg/kg), a specific high affinity MDR agonist, produced a dose-dependent hyperphagic effects. In contrast, neurosteroids pregnenolone sulfate (PS) (1-10 mg/kg) and dehydroepiandrosterone sulfate (DHEAS) (1-10 mg/kg) produced a hypophagic effect, in a dose-dependent manner. The allopregnanolone-, progesterone- and 4'-chlordiazepam-induced hyperphagic effect was blocked by picrotoxin (1 mg/kg), a GABA-A chloride channel antagonist, but not by flumazenil (2 mg/kg), a benzodiazepine (BZD) antagonist. The 4'-chlordiazepam-induced hyperphagic effect was prevented by pretreatment with PK11195 (2 mg/kg), a selective partial MDR antagonist. The hypophagic effect of DHEAS (10 mg/kg) was reversed by dizocilpine (10 microg/kg), an NMDA receptor antagonist, but resistant to muscimol (0.1 mg/kg), a selective GABA-A receptor agonist. In contrast, the PS (10 mg/kg)-induced hypophagic response was resistant to dizocilpine, but sensitive to muscimol (0.1 mg/kg). Both the sulfated neurosteroids PS and DHEAS also reversed the hyperphagic effect of allopregnanolone. In addition, the BZD agonist triazolam (0.05-0.25 mg/kg) also produced a flumazenil- and picrotoxin-sensitive hyperphagic effects, thereby suggesting the changes in feeding behavior by neurosteroids represent GABA-A receptor mediated hyperphagic action. Although the possible antistress or anxiolytic actions of neurosteroids may confound the hyperphagia, behavioral effects observed were specific to food because the mice were adopted to the test environment and diet, and of a possible variation between various neurosteroids in the

Emerging therapies to treat frailty syndrome in the elderly.

PubMed

Cherniack, E Paul; Florez, Hermes J; Troen, Bruce R

2007-09-01

Frailty syndrome (FS) has become increasingly recognized as a major predictor of co-morbidities and mortality in older individuals. Interventions with the potential to benefit frail elders include nutritional supplementation (vitamins D, carotenoids, creatine, dehydroepiandrosterone (DHEA), and beta-hydroxy-beta-methylbutyrate) and exercise modalities (tai chi and cobblestone walking). While these have not been explicitly tested for their impact on FS, vitamin D supplementation appears to offer significant promise in enhancing long-term health of the elderly. Exercise modalities such as tai chi and cobblestone walking, because of probable low risk and ease of participation, may also confer benefit. Additional studies are needed to investigate interventions that directly prevent, delay, and/or ameliorate frailty. Successful therapies may well involve multi-component approaches utilizing a combination of medication, nutritional supplementation, and exercise.

New PCOS-like phenotype in older infertile women of likely autoimmune adrenal etiology with high AMH but low androgens.

PubMed

Gleicher, Norbert; Kushnir, Vitaly A; Darmon, Sarah K; Wang, Qi; Zhang, Lin; Albertini, David F; Barad, David H

2017-03-01

How anti-Müllerian hormone (AMH) and testosterone (T) interrelate in infertile women is currently largely unknown. We, therefore, in a retrospective cohort study investigated how infertile women with high-AMH (AMH ≥75th quantile; n=144) and with normal-AMH (25th-75th quantile; n=313), stratified for low-T (total testosterone ≤19.0ng/dL), normal-T (19.0-29.0ng/dL) and high-T (>29.0ng/dL) phenotypically behaved. Patient age, follicle stimulating hormone (FSH), dehyroepiandrosterone (DHEA), DHEA sulphate (DHEAS), cortisol (C), adrenocorticotrophic hormone (ACTH), IVF outcomes, as well as inflammatory and immune panels were then compared between groups, with AMH and T as variables. We identified a previously unknown infertile PCOS-like phenotype, characterized by high-AMH but, atypically, low-T, with predisposition toward autoimmunity. It presents with incompatible high-AMH and low-T (<19.0ng/dL), is restricted to lean PCOS-like patients, presenting delayed for tertiary fertility services. Since also characterized by low DHEAS, low-T is likely of adrenal origina, and consequence of autoimmune adrenal insufficiency since also accompanied by low-C and evidence of autoimmunity. DHEA supplementation in such patients equalizes low- to normal-T and normalizes IVF cycle outcomes. Once recognized, this high-AMH/low-T phenotype is surprisingly common in tertiary fertility centers but, currently, goes unrecognized. Its likely adrenal autoimmune etiology offers interesting new directions for investigations of adrenals control over ovarian function via adrenal androgen production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Child Maltreatment and Gender Interactions as Predictors of Differential Neuroendocrine Profiles

PubMed Central

Doom, Jenalee R.; Cicchetti, Dante; Rogosch, Fred A.; Dackis, Melissa N.

2013-01-01

Summary Child maltreatment is a potent stressor associated with neuroendocrine dysregulation and increased risk for mental and physical disorders throughout the lifespan. Gender differences in stress reactivity and adult psychopathology prevalence may be related to sex-specific responsivity to stress. The purpose of this study is to examine whether gender interacts with the stress of maltreatment to produce differential neuroendocrine profiles in children. Participants included 137 maltreated and 110 nonmaltreated low-income, racially and ethnically diverse children (range: 7.9–10.9 years; M= 9.42 years; 52% male) who attended a summer research day camp. Saliva was collected 3 times across the day for 5 days for cortisol and dehydroepiandosterone (DHEA) analysis. Department of Human Services records were examined to determine the type, severity, chronicity, onset, and recency of maltreatment for children in the maltreated group. Significant interactions between gender and maltreatment pervasiveness predicted diurnal cortisol, DHEA, and cortisol/DHEA ratio levels. Elevated daily cortisol levels were reported for boys compared to girls in the group with more pervasive maltreatment. Boys with less pervasive maltreatment had lower DHEA and higher cortisol/DHEA ratio levels than girls with similar experiences, nonmaltreated boys, and boys with more pervasive maltreatment. Further results are consistent with down-regulation of cortisol production in girls with more pervasive maltreatment and girls who experienced maltreatment that was early onset and not recent. The effectiveness of interventions for maltreated children may be improved with greater knowledge of how maltreatment differentially affects neuroendocrine regulation by gender. PMID:23333253

The Role of Estrogen-Related Receptor Alpha in Steroidogenesis in the Breast

DTIC Science & Technology

2009-04-01

Bjarnason NH, Mitlak BH, et al., Effects of raloxifene on bone mineral density , serum cholesterol concentrations, and uterine endometrium in...synthesize DHEA from steroidogenic precursors. High -Performance Liquid chromatography was used to identify the steroids synthesized by HepG2 cells...Figure 2A. Additionally, a radioimmunoassay corroborated synthesis of DHEA from both pregnenolone and 22(R)-OH- cholesterol (Figure 2B and 2C). These

Placental sulfatase deficiency: maternal and fetal expression of steroid sulfatase deficiency and X-linked ichthyosis.

PubMed

Bradshaw, K D; Carr, B R

1986-07-01

PSD-X-linked ichthyosis are manifestations of a similar disorder of an inborn error of metabolism characterized by a deficiency of steroid sulfatase. The decreased enzyme activity is due to the absence of the expression of enzyme (steroid sulfatase) protein. Affected individuals with this disorder are males (X-linked inheritance) with a frequency of 1/2000 to 1/6000 births. Homozygous females from cosanguineous marriages have been reported with this disorder. The diagnosis is suspected and confirmed by: Low estriol excretion; Negative DHEAS loading test Increased DHEAS in amnionic fluid; Normal DHEAS in cord plasma; Possible delayed or abnormal labor patterns; Decreased sulfatase activity in the placenta, fibroblast, erythrocytes, lymphocytes or leukocytes of affected individuals; Development of ichthyosis in male infants at 2 to 3 months of age.

Evaluation of the glucocorticoid, mineralocorticoid, and adrenal androgen secretion dynamics in a large cohort of patients aged 6-18 years with transfusion-dependent β-thalassemia major, with an emphasis on the impact of cardiac iron load.

PubMed

Uçar, Ahmet; Öner, Nergiz; Özek, Gülcihan; Çetinçakmak, Mehmet Güli; Abuhandan, Mahmut; Yıldırım, Ali; Kaya, Cemil; Ünverdi, Sena; Emeksiz, Hamdi Cihan; Yılmaz, Yasin; Yetim, Aylin

2016-07-01

The variable presence of adrenal insufficiency (AI) due to hypocortisolemia (HC) in patients with thalassemia is well established; however, the prevalence of adrenocortical hypofunction (ACH) in the zona glomerulosa and zona reticularis of the adrenal cortex is unknown. To establish the prevalence of ACH, we examined the cortisol response to 1-µg and 250-µg ACTH tests, plasma aldosterone (A)/plasma renin activity (PRA) ratio, and serum dehydroepiandrosterone sulfate (DHEAS) levels in a large cohort of patients with thalassemia, and to investigate the impact of total body iron load (TBIL) on adrenocortical function. The setting used was University hospital and government-based tertiary care center. One hundred twenty-one (52 females) patients with β-thalassemia major (β-TM) and 72 healthy peers (38 females) were enrolled. The patients underwent a 250-µg cosyntropin test if their peak cortisol was <500 nmol/L in a 1-µg cosyntropin test. Magnetic resonance imaging (MRI) was performed to assess the MRI-based liver iron content and cardiac MRI T2* iron. The associations between ACH and TBIL were investigated. The patients with thalassemia had lower ACTH, cortisol, DHEAS, and A/PRA values compared with the controls (p < 0.001). Thirty-nine patients (32.2 %) had HC [primary (n = 1), central (n = 36), combined (n = 2)], and 47 (38.8 %) patients had reduced DHEAS levels; 29 (24.0 %) patients had reduced A/PRA ratios. Forty-six (38.0 %) patients had hypofunction in one of the adrenal zones, 26 (21.5 %) had hypofunction in two adrenal zones, and 9 (7.4 %) had hypofunction in all three zones. Patient age and TBIL surrogates were significant independent parameters associated with ACH. Cardiac MRI T2* iron was the only significant parameter that predicted the severity of ACH at a cut-off of 20.6 ms, with 81 % sensitivity and 78 % specificity. Patients with thalassemia have a high prevalence of AI due to HC and zona glomerulosa and zona reticularis

Eight-Week Training Cessation Suppresses Physiological Stress but Rapidly Impairs Health Metabolic Profiles and Aerobic Capacity in Elite Taekwondo Athletes.

PubMed

Liao, Yi-Hung; Sung, Yu-Chi; Chou, Chun-Chung; Chen, Chung-Yu

2016-01-01

Changes in an athlete's physiological and health metabolic profiles after detraining have not been studied in elite Taekwondo (TKD) athletes. To enable a better understanding of these physiological changes to training cessation, this study examined the effects of 8-weeks detraining on the aerobic capacity, body composition, inflammatory status and health metabolic profile in elite TKD athletes. Sixteen elite TKD athletes (age: 21.0 ± 0.8 yrs, BMI: 22.4 ± 3.9 kg/m2; Mean ± SD; 11 males and 5 females) participated in this study. Physical activity level assessment using computerized physical activity logs was performed during the competitive preparation season (i.e. one-week before national competition) and at two week intervals throughout the detraining period. Participant aerobic capacity, body fat, and blood biomarkers were measured before and after detraining, and the blood biomarker analyses included leukocyte subpopulations, blood glucose, insulin, dehydroepiandrosterone-sulfate (DHEA-S), and cortisol. Eight-week detraining increased DHEA-S/cortisol ratio (+57.3%, p = 0.004), increased insulin/cortisol ratio (+59.9%, p = 0.004), reduced aerobic power (-2.43%, p = 0.043), increased body fat accumulation (body fat%: +21.3%, p < 0.001), decreased muscle mass (muscle mass%: -4.04%, p < 0.001), and elevated HOMA-IR (the biomarker of systemic insulin resistance; +34.2%, p = 0.006). The neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory index, increased by 48.2% (p = 0.005). The change in aerobic capacity was correlated with the increased fat mass (r = -0.429, p = 0.049) but not with muscle loss. An increase in the NLR was correlated to the changes in HOMA-IR (r = 0.44, p = 0.044) and aerobic capacity (r = -0.439, p = 0.045). We demonstrate that 8-week detraining suppresses physiological stress but rapidly results in declines in athletic performance and health metabolic profiles, including reduced aerobic capacity, increased body fat, muscle loss, insulin

Atorvastatin treatment does not affect gonadal and adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia.

PubMed

Santini, Stefano A; Carrozza, Cinzia; Lulli, Paola; Zuppi, Cecilia; CarloTonolo, Gian; Musumeci, Salvatore

2003-01-01

Atorvastatin, a second generation synthetic 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia, reduces both intracellular cholesterol synthesis and serum cholesterol levels, and this could have a potential negative impact on gonadal and adrenal steroidogenesis. Hypercholesterolemia in type 2 diabetes, even when mild, must be treated in an aggressive way, due to the more strict therapeutic goals than in the non diabetic population. Since the wide use of 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor (statins) in type 2 diabetes, the main aim of our study was to evaluate the effects of "therapeutic" doses of atorvastatin on gonadal and adrenal hormones in 24 type 2 diabetic patients (16 males and 8 postmenopausal females), with mild to moderate hypercholesterolemia (LDL-cholesterol = 150.1 +/- 32.0 and 189.9 +/- 32.9 mg/dl, respectively) studied before and after a 3 months treatment with atorvastatin (20 mg/day). In all patients, lipids and serum cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstendione and sex hormone binding globulin (SHBG) were measured, with the addition, only in males, of testosterone and free testosterone index. After atorvastatin treatment a significant decrease in total and LDL cholesterol was observed (p < 0.05), while HDL-cholesterol did not significantly change ( p = N.S.), as no significant difference was found between steroid hormones measured before and after atorvastatin either in male and females. In conclusion, our data suggest that, in type 2 diabetic patients, the use of atorvastatin has no clinically important effects on either gonadal or adrenal steroid hormones.

Effects of Tribulus terrestris on endocrine sensitive organs in male and female Wistar rats.

PubMed

Martino-Andrade, Anderson J; Morais, Rosana N; Spercoski, Katherinne M; Rossi, Stefani C; Vechi, Marina F; Golin, Munisa; Lombardi, Natália F; Greca, Cláudio S; Dalsenter, Paulo R

2010-01-08

Investigate the possible effects of Tribulus terrestris (TT) on endocrine sensitive organs in intact and castrated male rats as well as in a post-menopausal rat model using ovariectomized females. Three different dose levels of TT (11, 42 and 110 mg/kg/day) were administered to castrated males for 7 days and to intact males and castrated females for 28 days. In addition to TT treatment, all experiments also included a group of rats treated with dehydroepiandrosterone (DHEA). In experiments using castrated males and females we also used testosterone and 17 alpha-ethynylestradiol, respectively, as positive controls for androgenicity and estrogenicity. Neither DHEA nor TT was able to stimulate androgen sensitive tissues like the prostate and seminal vesicle in both intact and castrated male rats. In addition, administration of TT to intact male rats for 28 days did not change serum testosterone levels as well as did not produce any quantitative change in the fecal excretion of androgenic metabolites. However, a slight increase in the number of homogenization-resistant spermatids was observed in rats treated with 11 mg/kg/day of TT extract. In ovariectomized females, TT did not produce any stimulatory effects in uterine and vaginal epithelia. Tribulus terrestris was not able to stimulate endocrine sensitive tissues such as the prostate, seminal vesicle, uterus and vagina in Wistar rats, indicating lack of androgenic and estrogenic activity in vivo. We also showed a positive effect of TT administration on rat sperm production, associated with unchanged levels of circulating androgens. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Stress-induced changes of neurosteroid profiles in rat brain and plasma under immobilized condition.

PubMed

Park, Myeong Hyeon; Rehman, Shaheed Ur; Kim, In Sook; Choi, Min Sun; Yoo, Hye Hyun

2017-05-10

In this study, various neurosteroids in brain and plasma were simultaneously determined using liquid chromatography-tandem mass spectrometry and their profile changes in a stress-induced rats were investigated. The investigated neurosteroids are as follows: progesterone (P4), 5α-dihydroprogesterone (5α-DHP), 5β-dihydroprogesterone, estrone, androstenedione (AE), cortisol, cortisone, corticosterone (CORT), dehydroepiandrosterone (DHEA), pregnanolone (3α,5β-THP), allopregnanolone (ALLO), 11-deoxycorticosterone (DOC), 11-deoxycortisol, pregnenolone (PREG), and 5α/5β-tetrahydrodeoxycorticosterone (5α/5β-THDOC). Brain and plasma samples were processed using solid-phase extraction with methanol and acetic acid (99:1), and derivatized with a hydroxylamine reagent. Separation was achieved within 13min at a flow rate of 0.4mL/min with a C18 column (3.0×50mm, 2.7μm). The triple quadrupole mass spectrometer was operated in the positive electrospray ionization mode. Using this method, the neurosteroid level variation was quantitated and investigated in the brain and plasma upon immobilization stress in rats. As a result, AE, CORT, DOC, P4, 5α-DHP, 5α/5β-THDOC, DHEA, 3α,5β-THP, ALLO, and PREG levels were significantly altered in both the brain and plasma samples when stress was induced. These findings demonstrated that stress leads to the alteration of the GABAergic neurosteroid profile. The present results will be helpful for furthering an understanding of the role of neurosteroids in stressed conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of efficacy of metformin and oral contraceptive combination of ethinyl estradiol and drospirenone in polycystic ovary syndrome.

PubMed

Suvarna, Yashasvi; Maity, Nivedita; Kalra, Pramila; Shivamurthy, M C

2016-01-01

The 2013 Endocrine Society guidelines state that hormonal contraceptives should be used for treating both menstrual irregularity and hirsutism in patients with polycystic ovary syndrome (PCOS). Metformin should be reserved for the treatment of women presenting with only menstrual irregularity because it has limited benefits in treating hyperandrogenism associated with PCOS. A high prevalence of insulin resistance is noted among the South Asians, and these guidelines may not hold good for this population. Thus, this study was conducted to investigate and compare the effects of metformin and an oral contraceptive containing drospirenone on menstrual pattern, body mass index, serum testosterone levels, and dehydroepiandrosterone sulfate (DHEAS) levels at baseline to 6 months of therapy in the treatment groups. This was a prospective observational study that was conducted over a year in patients visiting the Endocrinology outpatient department at a tertiary care center in a south Indian city. Forty-six subjects diagnosed with PCOS as per the Rotterdam criteria were included. They received either metformin twice daily or an oral contraceptive containing drospirenone once daily as a monthly regimen for 6 months. Metformin regularized menstrual cycles in 72% of patients who were followed up at 6 months. No significant difference was observed between the two treatment groups with respect to decreasing the body mass index, serum testosterone levels, and DHEAS levels (p=0.40, p=0.65, and p=0.22, respectively). Metformin is effective in regularizing menstrual cycles, decreasing body mass index, and treating hyperandrogenism in Indian women diagnosed with PCOS.

Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone.

PubMed

Saggese, G; Cesaretti, G; Franchi, G; Startari, L

1996-08-01

Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I, GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which , for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 < p < 0.05) in nutritional obesity than in the other groups. Considering all

Male sex steroids and hormonal control of male courtship behavior in the yellow-bellied slider turtle, Trachemys scripta

USGS Publications Warehouse

Garstka, W.R.; Cooper, W.E.; Wasmund, K.W.; Lovich, J.E.

1991-01-01

Survey of androgens and estrogens in serum, liver and testes of male yellow-bellied slider turtles, Trachemys (= Pseudemys) scripta, a species exhibiting dissociated gametogenesis age-dependent melanism, revealed the presence of numerous androgen precursors, androgens, androgen metabolites, and estrogens in quantities varying with season, tissue, and male coloration.The most commonly found and abundant androgens in all males were dehydroepiandrosterone (DHEA) and androstenedione, which were present at significantly higher levels in testes than in serum or liver.Epitestosterone was found in the serum and liver of only melanistic males; testosterone was only rarely recovered.Behavioral testing of castrated male turtles implanted with various androgens, as well as intact and sham-operated controls, revealed that melanistic males courted more frequently than nonmelanistic males, and that exogenous testosterone was most effective in inducing courtship behavior in castrated males.

In PCOS, adrenal steroids are regulated differently in the morning vs. in response to nutrient intake

PubMed Central

Gurusinghe, Dumindra; Gill, Sharan; Almario, Rogelio U.; Lee, Jennifer; Horn, William F.; Keim, Nancy L; Kim, Kyoungmi; Karakas, Sidika E.

2010-01-01

Objective To investigate adrenal steroid regulation in PCOS Design 5-hour oral glucose tolerance test (OGTT) and frequently sampled-intravenous GTT Setting University research center Patients Thirty patients Intervention None Main outcome measures Anthropometrics, leptin, cortisol, DHEAS, glucose, insulin Results Morning cortisol correlated with sensitivity index (SI, r=0.540, p=0.0109), DHEAS correlated inversely with age (r=−0.6359), body mass index (BMI, r=−0.6199), fat mass (r=−0.630) and leptin (r=−0.5676) (p< 0.002 for all). Between the 2nd and 4th hour of OGTT, cortisol changes (Δ) exhibited 3 patterns: I. Responders (n=9, Δ:10.7±1.0μg/dL), II. Non-responders (n=10, Δ:−3.5±0.6μg/dL), III. Intermediates (n=11, Δ:4.3±1.0μg/dL). Compared to non-responders, responders were more obese (BMI: 37.0±1.6 vs. 31.7±1.8kg/m2, p< 0.05); had higher leptin (28.9±1.7 vs. 24.1±1.1ng/mL, p<0.03) and lower DHEAS (133±12 vs. 236±32ng/mL, p<0.01), higher glucose at 1h of OGTT (195±13 vs. 131±12mg/dL, p< 0.05), higher AUCGlucose (332±20 vs. 265±17mg/dL, p=0.0208), higher AUCInsulin (244±50 vs. 125±30μU/mL, p=0.05) and lower nadir glucose (61±2 vs. 70±2mg/dL, p=0.0002). Conclusion Obesity and insulin resistance are associated with lower morning cortisol and DHEAS but increased cortisol and DHEA responses after glucose ingestion. Morning steroid levels may not reflect the day-long exposure. PMID:19342030

Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men.

PubMed

Brambilla, Donald J; O'Donnell, Amy B; Matsumoto, Alvin M; McKinlay, John B

2007-12-01

Estimates of intraindividual variation in hormone levels provide the basis for interpreting hormone measurements clinically and for developing eligibility criteria for trials of hormone replacement therapy. However, reliable systematic estimates of such variation are lacking. To estimate intraindividual variation of serum total, free and bioavailable testosterone (T), dihydrotestosterone (DHT), SHBG, LH, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), oestrone, oestradiol and cortisol, and the contributions of biological and assay variation to the total. Paired blood samples were obtained 1-3 days apart at entry and again 3 months and 6 months later (maximum six samples per subject). Each sample consisted of a pool of equal aliquots of two blood draws 20 min apart. Men aged 30-79 years were randomly selected from the respondents to the Boston Area Community Health Survey, a study of the health of the general population of Boston, MA, USA. Analysis was based on 132 men, including 121 who completed all six visits, 8 who completed the first two visits and 3 who completed the first four visits. Day-to-day and 3-month (long-term) intraindividual standard deviations, after transforming measurements to logarithms to eliminate the contribution of hormone level to intraindividual variation. Biological variation generally accounted for more of total intraindividual variation than did assay variation. Day-to-day biological variation accounted for more of the total than did long-term biological variation. Short-term variability was greater in hormones with pulsatile secretion (e.g. LH) than those that exhibit less ultradian variation. Depending on the hormone, the intraindividual standard deviations imply that a clinician can expect to see a difference exceeding 18-28% about half the time when two measurements are made on a subject. The difference will exceed 27-54% about a quarter of the time. Given the level of intraindividual variability in hormone

Cognitive function, stress hormones, heart rate and nutritional status during simulated captivity in military survival training.

PubMed

Lieberman, Harris R; Farina, Emily K; Caldwell, John; Williams, Kelly W; Thompson, Lauren A; Niro, Philip J; Grohmann, Kyle A; McClung, James P

2016-10-15

Stress influences numerous psychological and physiological processes, and its effects have practical implications in a variety of professions and real-world activities. However, few studies have concurrently assessed multiple behavioral, hormonal, nutritional and heart-rate responses of humans to acute, severe stress. This investigation simultaneously assessed cognitive, affective, hormonal, and heart-rate responses induced by an intensely stressful real-world environment designed to simulate wartime captivity. Sixty males were evaluated during and immediately following participation in U.S. Army Survival, Evasion, Resistance, and Escape (SERE) school, three weeks of intense but standardized training for Soldiers at risk of capture. Simulated captivity and intense mock interrogations degraded grammatical reasoning (p<0.005), sustained-attention (p<0.001), working memory (p<0.05) and all aspects of mood assessed by the Profile of Mood States (POMS) questionnaire: Tension/Anxiety, Depression/Dejection, Anger/Hostility, Vigor/Activity, Fatigue/Inertia; Confusion/Bewilderment, and Total Mood Disturbance (p<0.001) It also elevated heart rate (p<0.001); increased serum and salivary cortisol and dehydroepiandrosterone-sulfate (DHEA-s) (p<0.01); elevated serum epinephrine, norepinephrine, and soluble transferrin receptors (sTfR) (p<0.01); increased salivary neuropeptide-Y (NPY) (p<0.001); and decreased serum prolactin and serum and salivary testosterone (p<0.001). Partial recovery was observed immediately after training, but stress-induced changes, particularly in body weight and several of the biomarkers, persisted. This study demonstrates that when individuals were exposed to realistic and controlled simulated captivity, cognition, mood, stress hormones, nutritional status and heart rate are simultaneously altered, and each of these subsequently recovers at different rates. Published by Elsevier Inc.

Multiple Hormonal Dysregulation as Determinant of Low Physical Performance and Mobility in Older Persons

PubMed Central

Maggio, Marcello; Lauretani, Fulvio; De Vita, Francesca; Basaria, Shehzad; Lippi, Giuseppe; Buttò, Valeria; Luci, Michele; Cattabiani, Chiara; Ceresini, Graziano; Verzicco, Ignazio; Ferrucci, Luigi; Ceda, Gian Paolo

2015-01-01

Mobility-disability is a common condition in older individuals. Many factors, including the age-related hormonal dysregulation, may concur to the development of disability in the elderly. In fact, during the aging process it is observed an imbalance between anabolic hormones that decrease (testosterone, dehydroepiandrosterone sulphate (DHEAS), estradiol, insulin like growth factor-1 (IGF-1) and Vitamin D) and catabolic hormones (cortisol, thyroid hormones) that increase. We start this review focusing on the mechanisms by which anabolic and catabolic hormones may affect physical performance and mobility. To address the role of the hormonal dysregulation to mobility-disability, we start to discuss the contribution of the single hormonal derangement. The studies used in this review were selected according to the period of time of publication, ranging from 2002 to 2013, and the age of the participants (≥65 years). We devoted particular attention to the effects of anabolic hormones (DHEAS, testosterone, estradiol, Vitamin D and IGF-1) on both skeletal muscle mass and strength, as well as other objective indicators of physical performance. We also analyzed the reasons beyond the inconclusive data coming from RCTs using sex hormones, thyroid hormones, and vitamin D (dosage, duration of treatment, baseline hormonal values and reached hormonal levels). We finally hypothesized that the parallel decline of anabolic hormones has a higher impact than a single hormonal derangement on adverse mobility outcomes in older population. Given the multifactorial origin of low mobility, we underlined the need of future synergistic optional treatments (micronutrients and exercise) to improve the effectiveness of hormonal treatment and to safely ameliorate the anabolic hormonal status and mobility in older individuals. PMID:24050169

Sex-specific associations of testosterone with prefrontal-hippocampal development and executive function.

PubMed

Nguyen, Tuong-Vi; Lew, Jimin; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Fonov, Vladimir S; Collins, D Louis; Ducharme, Simon; McCracken, James T

2017-02-01

Testosterone is thought to play a crucial role in mediating sexual differentiation of brain structures. Examinations of the cognitive effects of testosterone have also shown beneficial and potentially sex-specific effects on executive function and mnemonic processes. Yet these findings remain limited by an incomplete understanding of the critical timing and brain regions most affected by testosterone, the lack of documented links between testosterone-related structural brain changes and cognition, and the difficulty in distinguishing the effects of testosterone from those of related sex steroids such as of estradiol and dehydroepiandrosterone (DHEA). Here we examined associations between testosterone, cortico-hippocampal structural covariance, executive function (Behavior Rating Inventory of Executive Function) and verbal memory (California Verbal Learning Test-Children's Version), in a longitudinal sample of typically developing children and adolescents 6-22 yo, controlling for the effects of estradiol, DHEA, pubertal stage, collection time, age, handedness, and total brain volume. We found prefrontal-hippocampal covariance to vary as a function of testosterone levels, but only in boys. Boys also showed a specific association between positive prefrontal-hippocampal covariance (as seen at higher testosterone levels) and lower performance on specific components of executive function (monitoring the action process and flexibly shifting between actions). We also found the association between testosterone and a specific aspect of executive function (monitoring) to be significantly mediated by prefrontal-hippocampal structural covariance. There were no significant associations between testosterone-related cortico-hippocampal covariance and verbal memory. Taken together, these findings highlight the developmental importance of testosterone in supporting sexual differentiation of the brain and sex-specific executive function. Copyright © 2016 Elsevier Ltd. All rights

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

PubMed

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

2011-12-01

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

Chronic stress and sexual function in women.

PubMed

Hamilton, Lisa Dawn; Meston, Cindy M

2013-10-01

Chronic stress is known to have negative effects on reproduction, but little is known about how it affects the sexual response cycle. The present study examined the relationship between chronic stress and sexual arousal and the mechanisms that mediate this relationship. The aim of this study is to test the relationship between chronic stress and sexual arousal and identify mechanisms that may explain this relationship. We predicted that women experiencing high levels of chronic stress would show lower levels of genital arousal and dehydroepiandrosterone (DHEAS) and higher levels of cortisol and cognitive distraction compared with women with average levels of stress. Women who were categorized as high in chronic stress (high stress group; n=15) or average in chronic stress (average stress group; n=15) provided saliva samples and watched an erotic film while having their genital and psychological arousal measured. Main outcome measures were vaginal pulse amplitude, psychological arousal, salivary cortisol, salivary DHEAS, and heart rate and compared them between women with high and average levels of chronic stress. Women in the high stress group had lower levels of genital, but not psychological arousal, had higher levels of cortisol, and reported more distraction during the erotic film than women in the average stress group. The main predictor of decreased genital sexual arousal was participants' distraction scores. High levels of chronic stress were related to lower levels of genital sexual arousal. Both psychological (distraction) and hormonal (increased cortisol) factors were related to the lower levels of sexual arousal seen in women high in chronic stress, but distraction was the only significant predictor when controlling for other variables. © 2013 International Society for Sexual Medicine.

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.

Effects of G6PD activity inhibition on the viability, ROS generation and mechanical properties of cervical cancer cells.

PubMed

Fang, Zishui; Jiang, Chengrui; Feng, Yi; Chen, Rixin; Lin, Xiaoying; Zhang, Zhiqiang; Han, Luhao; Chen, Xiaodan; Li, Hongyi; Guo, Yibin; Jiang, Weiying

2016-09-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been revealed to be involved in the efficacy to anti-cancer therapy but the mechanism remains unclear. We aimed to investigate the anti-cancer mechanism of G6PD deficiency. In our study, dehydroepiandrosterone (DHEA) and shRNA technology were used for inhibiting the activity of G6PD of cervical cancer cells. Peak Force QNM Atomic Force Microscopy was used to assess the changes of topography and biomechanical properties of cells and detect the effects on living cells in a natural aqueous environment. Flow cytometry was used to detect the apoptosis and reactive oxygen species (ROS) generation. Scanning electron microscopy was used to observe cell morphology. Moreover, a laser scanning confocal microscope was used to observe the alterations in cytoskeleton to explore the involved mechanism. When G6PD was inhibited by DHEA or RNA interference, the abnormal Young's modulus and increased roughness of cell membrane were observed in HeLa cells, as well as the idioblasts. Simultaneously, G6PD deficiency resulted in decreased HeLa cells migration and proliferation ability but increased ROS generation inducing apoptosis. What's more, the inhibition of G6PD activity caused the disorganization of microfilaments and microtubules of cytoskeletons and cell shrinkage. Our results indicated the anti-cervix cancer mechanism of G6PD deficiency may be involved with the decreased cancer cells migration and proliferation ability as a result of abnormal reorganization of cell cytoskeleton and abnormal biomechanical properties caused by the increased ROS. Suppression of G6PD may be a promising strategy in developing novel therapeutic methods for cervical cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Associations between testicular hormones at adolescence and attendance at chlorinated swimming pools during childhood

PubMed Central

Nickmilder, M; Bernard, A

2011-01-01

The goal was to evaluate the associations between testicular hormones at adolescence and the exposure to chlorination by-products when attending chlorinated swimming pools. We obtained serum samples from 361 school male adolescents (aged 14–18 years) who had visited swimming pools disinfected with chlorine or by copper–silver ionization. We analysed serum concentrations of inhibin B (two different assays), total and free testosterone, sex hormone-binding globulin, luteinizing hormone (LH), follicle stimulating hormone (FSH) and dehydroepiandrosterone sulphate (DHEAS). There were strong inverse associations between serum levels of inhibin B (both assays) or of total testosterone, adjusted or unadjusted for gonadotropins and the time adolescents had spent in indoor chlorinated pools, especially during their childhood. Adolescents having attended indoor chlorinated pools for more than 250 h before the age of 10 years or for more than 125 h before the age of 7 years were about three times more likely to have an abnormally low serum inhibin B and/or total testosterone (<10th percentile) than their peers who never visited this type of pool during their childhood (odds ratio, 95% CI, 2.83, 1.06–7.52, p = 0.04 and 3.67, 1.45–9.34, p = 0.006, respectively). Such associations were not seen with free testosterone, LH, FSH and DHEAS or with the attendance of outdoor chlorinated pools or of the copper–silver pool. Swimming in indoor chlorinated pools during childhood is strongly associated with lower levels of serum inhibin B and total testosterone. The absorption of reprotoxic chlorination by-products across the highly permeable scrotum might explain these associations. PMID:21631527

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

PubMed

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

2015-06-01

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

Effects of two estroprogestins containing ethynilestradiol 30 microg and drospirenone 3 mg and ethynilestradiol 30 microg and chlormadinone 2 mg on skin and hormonal hyperandrogenic manifestations.

PubMed

Lello, Stefano; Primavera, Grazia; Colonna, Laura; Vittori, Giorgio; Guardianelli, Francesca; Sorge, Roberto; Raskovic, Desanka

2008-12-01

Hyperandrogenic manifestation in women, such as seborrhea, acne and increased hair growth are common reasons of psychological distress. Skin appearance is very important for young women. This study evaluated the hormonal and skin effects of two estroprogestins (EPs) containing ethinyl-estradiol (EE) 30 microg associated with drospirenone (DRSP) 3 mg or chlormadinone acetate (CMA) 2 mg, respectively. Fifty-five women with signs and symptoms of hyperandrogenism (seborrhea, acne and increased hair growth) were enrolled in the study; randomly, 30 women were treated with EE 30 microg + DRSP 3 mg and 25 with EE 30 microg + CMA 2 mg. Follicle-stimulating hormone (FSH), luteinising hormone (LH), 17-hydroxyprogesterone (17OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG) and free androgen index (T x 100/SHBG, FAI) were assessed at baseline, and after 3 and 6 months of treatment with EPs. Effects on seborrhea, acne and increased hair growth (as Ferriman-Gallwey score) were also evaluated at the same time points. Finally, skin hydration, transepidermal water loss (TEWL) and skin homogeneity were studied with non-invasive technique during the study. Treatment for 6 months with both EPs decreased significantly the circulating androgen levels (A, T, DHEAS) and FAI, and increased SHBG levels; also skin pattern was improved. EP containing EE and DRSP was better than EP containing EE and CMA as for skin changes, as seborrhea, acne, increased hair, hydration, homogeneity and overall quality of the skin; moreover, hormonal changes (as FAI) under therapy were more pronounced with EE/DRSP than EE/CMA. These effects may be considered in EP choice and could be important in improving patient's compliance and quality of life in hyperandrogenic women.

Multiple hormonal dysregulation as determinant of low physical performance and mobility in older persons.

PubMed

Maggio, Marcello; Lauretani, Fulvio; De Vita, Francesca; Basaria, Shehzad; Lippi, Giuseppe; Butto, Valeria; Luci, Michele; Cattabiani, Chiara; Ceresini, Graziano; Verzicco, Ignazio; Ferrucci, Luigi; Ceda, Gian Paolo

2014-01-01

Mobility-disability is a common condition in older individuals. Many factors, including the age-related hormonal dysregulation, may concur to the development of disability in the elderly. In fact, during the aging process it is observed an imbalance between anabolic hormones that decrease (testosterone, dehydroepiandrosterone sulphate (DHEAS), estradiol, insulin like growth factor-1 (IGF-1) and Vitamin D) and catabolic hormones (cortisol, thyroid hormones) that increase. We start this review focusing on the mechanisms by which anabolic and catabolic hormones may affect physical performance and mobility. To address the role of the hormonal dysregulation to mobility-disability, we start to discuss the contribution of the single hormonal derangement. The studies used in this review were selected according to the period of time of publication, ranging from 2002 to 2013, and the age of the participants (≥65 years). We devoted particular attention to the effects of anabolic hormones (DHEAS, testosterone, estradiol, Vitamin D and IGF-1) on both skeletal muscle mass and strength, as well as other objective indicators of physical performance. We also analyzed the reasons beyond the inconclusive data coming from RCTs using sex hormones, thyroid hormones, and vitamin D (dosage, duration of treatment, baseline hormonal values and reached hormonal levels). We finally hypothesized that the parallel decline of anabolic hormones has a higher impact than a single hormonal derangement on adverse mobility outcomes in older population. Given the multifactorial origin of low mobility, we underlined the need of future synergistic optional treatments (micronutrients and exercise) to improve the effectiveness of hormonal treatment and to safely ameliorate the anabolic hormonal status and mobility in older individuals.

Cross-sectional study of the determinants and associations of sex hormone-binding globulin concentrations in first degree relatives (FDR) of patients with Type 2 Diabetes Mellitus.

PubMed

Abdella, N A; Mojiminiyi, O A

2017-11-01

This study explores the determinants of sex hormone binding globulin (SHBG) and associations with categories of glucose intolerance and undiagnosed diabetes in first-degree relatives (FDR) of patients with Type 2 Diabetes Mellitus (T2D). Anthropometric indices, fasting lipids, glucose, insulin, adiponectin, leptin, SHBG, estradiol (E2), testosterone (TT), androstenedione (AND), dehydroepiandrosterone sulphate (DHEA-S), high-sensitivity C-reactive protein (hs-CRP) and alanine aminotransferase (ALT) were measured in 584 FDR. Homeostasis model assessment-estimate of insulin resistance (HOMA-IR), beta cell function (%B), insulin sensitivity (%S) and free androgen index (FAI) were calculated. 266 subjects were normoglycemic; 237 had prediabetes and 81 had undiagnosed diabetes. SHBG decreased stepwise with worsening categories of glucose intolerance in females whereas FAI decreased stepwise with worsening categories in males only. SHBG showed significant positive correlations with adiponectin, and HDL-C and significant negative correlations with body mass index (BMI), waist circumference (WC), Waist:hip ratio (WHR), ALT, triglycerides (TG), %B, leptin and FAI. After adjustment for WHR, only HDL-C and FAI in men and FAI and HbA1c in females remained significantly associated with SHBG. Receiver Operating Characteristic (ROC) curve analysis for detection of diabetes showed that areas under the curve for FAI and SHBG were 0.711 and 0.386 for males and 0.430 and 0.660 for females respectively. Associations of SHBG with some anthropometric and metabolic variables in FDR suggests that lower levels is a marker for risk of developing T2D through obesity dependent metabolic pathways but low FAI is a better marker of state of diabetes in males. Copyright © 2017 Elsevier B.V. All rights reserved.

Dimensions of Adversity, Physiological Reactivity, and Externalizing Psychopathology in Adolescence: Deprivation and Threat

PubMed Central

Busso, Daniel S.; McLaughlin, Katie A.; Sheridan, Margaret A.

2016-01-01

Objective Dysregulation of autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis function is a putative intermediate phenotype linking childhood adversity (CA) with later psychopathology. However, associations of CAs with ANS and HPA-axis function vary widely across studies. Here, we test a novel conceptual model discriminating between distinct forms of CA (deprivation and threat) and examine their independent associations with physiological reactivity and psychopathology. Methods Adolescents (N = 169; mean age = 14.9 years; S.D.=1.4) with a range of interpersonal violence (e.g., maltreatment, community violence) and poverty exposure participated in the Trier Social Stress Test (TSST). During the TSST, electrocardiogram, impedance cardiograph, salivary cortisol and dehydroepiandrosterone-sulphate (DHEA-S) data were collected. We compared the associations of poverty (an indicator of deprivation) and interpersonal violence (an indicator of threat) on sympathetic, parasympathetic, and HPA-axis reactivity to the TSST, and assessed whether these differences mediated the association of adversity with internalizing and externalizing symptoms. Results Exposure to poverty and interpersonal violence was associated with psychopathology. Interpersonal violence, adjusting for poverty, was associated with blunted sympathetic (β=1.44, p=.050) and HPA-axis reactivity (β=−.09, p=.021). Blunted cortisol reactivity mediated the association of interpersonal violence with externalizing, but not internalizing, psychopathology. In contrast, poverty was not associated with physiological reactivity after adjusting for interpersonal violence. Conclusions We provide evidence for distinct neurobiological mechanisms through which adversity related to poverty and interpersonal violence are associated with psychopathology in adolescence. Distinguishing distinct pathways through which adversity influences mental health has implications for preventive interventions

Anti-Aging Effects of Some Selected Iranian Folk Medicinal Herbs-Biochemical Evidences

PubMed Central

Mohammadirad, Azadeh; Aghamohammadali-Sarraf, Fatemeh; Badiei, Simin; Faraji, Zakie; Hajiaghaee, Reza; Baeeri, Maryam; Gholami, Mahdi; Abdollahi, Mohammad

2013-01-01

Objective(s): In the current study, the effects of selected folk medicinal herbs were evaluated in D-galactose-induced aging in male mice. Materials and Methods: Male BALB/c mice were randomly divided into 12 groups composing sham, control, and treated groups. Aging was induced by administration of D-galactose (500 mg/kg/day for 6 weeks). A positive control group was assigned that received vitamin E (200 mg/kg/day). The extract of herbs was prepared, lyophilized, and used in this study. The herbs were administered by gavage for 4 weeks to D-galactose-aged animals at the selected doses (mg/kg/day) as follows: Zingiber officinale (250), Glycyrrhiza glabra (150), Rosmarinus officinalis (300), Peganum harmala (50), Aloe vera (150), Satureja hortensis (200), Teucrium scordium (200), Hypericum perforatum (135) and Silybum marianum (150). One group of animals was assigned as sham and not given D-galactose. Results: At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1β (IL-β), interlukine-6 (IL-6), NF-kappaB (NF-κb), total antioxidant power (TAP), thiobarbituric acid reactive substances (TBARS) as lipid peroxidation (LPO) marker and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood. Conclusion: These data for the first time indicate significant anti-aging potential of examined herbs. Results showed that D-galactose induces a significant oxidative stress and promotes proinflammatory cascade of aging while all herbs more or less recovered these changes. Among 9 herbal extracts, Silybum marianum showed the best effect in restoring aging changes. PMID:24494070

Association of baseline sex hormone levels with baseline and longitudinal changes in waist-to-hip ratio: Multi-Ethnic Study of Atherosclerosis.

PubMed

Vaidya, D; Dobs, A; Gapstur, S M; Golden, S H; Cushman, M; Liu, K; Ouyang, P

2012-12-01

Waist-to-hip ratio (WHR) is strongly associated with prevalent atherosclerosis. We analyzed the associations of baseline serum levels of testosterone (T), estradiol (E2), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA) with WHR in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Baseline data was available for 3144 men and 2038 postmenopausal women, who were non-users of hormone therapy, who were 45-84 years of age, and of White, Chinese, Black or Hispanic racial/ethnic groups. Of these, 2708 men and 1678 women also had longitudinal measurements of WHR measured at the second and/or the third study visits (median follow-up 578 days and 1135 days, respectively). In cross-sectional analyses adjusted for age, race and cardiovascular disease risk factors, T was negatively associated with baseline WHR in men, whereas in both sexes, E2 was positively associated and SHBG was negatively associated with WHR (all P<0.001). In longitudinal analyses, further adjusted for follow-up time and baseline WHR, baseline T was negatively associated with WHR at follow-up (P=0.001) in men, whereas in both sexes, E2 was positively associated (P=0.004) and SHBG was negatively associated with WHR (P<0.001). The longitudinal association of E2, but not T, was independent of SHBG. In cross-sectional or longitudinal analyses, there were no associations between DHEA and WHR in either men or women. Sex hormones are associated with WHR at baseline and also during follow-up above and beyond their baseline association. Future research is needed to determine if manipulation of hormones is associated with changes in central obesity.

Hydroxylative activity of Aspergillus niger towards androst-4-ene and androst-5-ene steroids.

PubMed

Świzdor, Alina; Panek, Anna; Milecka-Tronina, Natalia

2017-10-01

Aspergillus niger, one of fungal species most frequently used for experimental and industrial-scale biotransformations of various organic compounds, is generally known to transform steroids at 16β position. In this work, application of the strain A. niger KCH910 to bioconversion of dehydroepiandrosterone (DHEA), androstenediol and testosterone is described, with emphasis on the metabolic steps leading to the products. Evidence from this study indicated that incubated 5-ene steroids underwent bioconversion within two metabolic pathways: oxidation by the action of 3β-HSD (3β-hydroxysteroid dehydrogenase) to 4-ene steroids, and minor allylic hydroxylation to epimeric 7-alcohols. Further transformation of the 3-oxo-4-ene metabolites resulted in non-selective 16-hydroxylation. It is the first report on an A. niger strain able to introduce not only 16β- but also 16α-hydroxyl function into steroids. Copyright © 2017. Published by Elsevier Inc.

Adrenal androgen secretion and dopaminergic activity in anorexia nervosa.

PubMed

Devesa, J; Pérez-Fernández, R; Bokser, L; Gaudiero, G J; Lima, L; Casanueva, F F

1988-01-01

The aim of the present study was to investigate if the postulated deficient adrenal androgen secretion in Anorexia Nervosa (AN), could be associated with a status of sustained dopaminergic hyperactivity. The adrenal responses to ACTH and PRL response to dopaminergic receptor blockade were studied in seven patients with Anorexia Nervosa and seven regularly menstruating women. AN patients showed lower baseline DHEA-sulphate (DHEA-S), androstenedione (Adione) and prolactin (PRL) levels than controls. The response to ACTH revealed evidences of significantly decreased 17-20 desmolase activity in AN, with apparent predominance of glucocorticoid over androgenic pathways relative to controls. Because dopaminergic receptor blockade with Domperidone (DOM) showed intense dopaminergic hyperactivity in AN, we postulate that the adrenal regression seen in the disease is the consequence of a reduced zona reticularis as a consequence of the lack of trophic support by PRL and/or intermediate lobe proopiomelanocortin (IL-POMC). This is consistent with our previous results in pre-adrenarchal dogs and rabbits.

Healthy community-living older men differ from women in associations between myostatin levels and skeletal muscle mass.

PubMed

Peng, Li-Ning; Lee, Wei-Ju; Liu, Li-Kuo; Lin, Ming-Hsien; Chen, Liang-Kung

2018-04-13

Myostatin is a negative regulator of muscle growth but the relationship between serum myostatin levels and muscle mass is unclear. This study investigated the association between serum myostatin levels and skeletal muscle mass among healthy older community residents in Taiwan, to evaluate the potential of serum myostatin as a biomarker for diagnosing sarcopenia and/or evaluating the effect of its treatment. Study data were excerpted from a random subsample of the I-Lan Longitudinal Aging Study population. Serum myostatin levels were determined and categorized into tertiles (low, medium, high). Relative appendicular skeletal muscle mass (RASM) was calculated as appendicular lean body mass by dual-energy X-ray absorptiometry divided by height squared (kg/m 2 ). Low muscle mass was defined as recommended by the Asian Working Group for Sarcopenia. The analytic study sample comprised 463 adults (mean age: 69.1 years; 49.5% men). Compared with subjects with normal RASM, those with lower RASM were older and frailer, with significantly higher prevalence of malnutrition, lower serum dehydroepiandrosterone (DHEA) levels, and were more likely to have low serum myostatin status. Multivariable logistic regression analysis showed that male sex (OR 3.60, 95% CI 1.30-9.92), malnutrition (OR 4.39, 95% CI 1.56-12.36), DHEA (OR 0.99, 95% CI 0.99-1.00), and low myostatin (OR 3.23, 95% CI 1.49-7.01) were all independent risk factors for low RASM (all P < 0.05). In men, DHEA (OR 0.99, 95% CI 0.98-1.00) and low myostatin (OR 4.89, 95% CI 1.79-13.37) were significantly associated with low RASM (both P < 0.05); however, only malnutrition was associated with low RASM in women (OR 13.59, 95% CI 2.22-83.25, P < 0.05). Among healthy community-living older adults, low serum myostatin levels were associated with low skeletal muscle mass in men, but not in women. Our results do not support using serum myostatin levels to diagnose sarcopenia, or to monitor how it responds to treatments

Psychophysiological correlates of cognitive deficits in family caregivers of patients with Alzheimer Disease.

PubMed

Corrêa, M S; Vedovelli, K; Giacobbo, B L; de Souza, C E B; Ferrari, P; de Lima Argimon, I I; Walz, J C; Kapczinski, F; Bromberg, E

2015-02-12

The progressive loss of memory and autonomy of Alzheimer's Disease (AD) patients, together with their characteristic behavioral and psychological symptoms, subjects their family caregivers to chronic stress. Several studies indicate that these caregivers are predisposed to cognitive impairments, but the physiological correlates of these alterations remain to be elucidated. Analyze the effects of chronic stress of family caregivers of AD patients on cognition, cortisol/DHEA ratios and BDNF levels and investigate the relation between these variables. Seventeen family caregivers (64.83 ± 3.64 years) of patients with AD and eighteen non-caregivers (58.29 ± 3.16 years) completed stress, depression and anxiety inventories. Exclusion criteria were current neurological disorders, major unstable medical illnesses, use of medications that could interfere with cognitive or HPA axis function and dementia. Attention, working memory and executive function were assessed with Digit Span and Trail Making tests, and declarative memory was analyzed with the Logical Memory test. Saliva was collected at 8 AM and 10 PM and its cortisol and DHEA levels determined by radioimmunoassay. Serum BDNF levels were measured by sandwich-ELISA. Results were analyzed with independent samples t test, covariance analysis and linear regressions. The statistical significance was set at p<0.05 and all p values were adjusted with Holm's Method. Caregivers showed more stress, depression and anxiety symptoms than non-caregivers, as well as significantly worse performances on attention, working memory and executive function tests. Caregivers also had higher cortisol/DHEA ratios and lower BDNF levels than non-caregivers. Cortisol/DHEA ratios, especially at 10 PM, were negatively related with all cognitive tasks in which caregivers showed impaired performance. On the other hand, the only cognitive task that related with the BDNF level was digit span. This study showed that caregivers' cognitive impairment is

[Androgen levels, parenting styles and aggressive behavior in 5-6-year-old boys and girls].

PubMed

Sánchez-Martín, José R; Azurmendi Imaz, Aitziber; Fano Ardanaz, Eduardo; Braza Lloret, Francisco; Muñoz Sánchez, José M; Carreras de Alba, María R

2009-02-01

Androgen levels, parenting styles and aggressive behavior in 5-6-year-old boys and girls. This study explores the relationship between androgen levels, parenting styles, and physical, verbal, and indirect aggression measures in 5-6-year-old children. 129 children (60 boys and 69 girls) were assessed in relation to their aggression levels using a peer-rating technique. Parents completed the Parenting Styles and Dimensions Questionnaire, from which the different parenting styles were obtained. Testosterone, androstenedione and dehydroepiandrosterone (DHEA) were measured using an enzymoimmunoassay technique in saliva samples. A regression analysis indicated that the directive mother-androstenedione interaction at the age of 5 was predictive of physical aggression at the age of 6. In specific terms, the results showed that, in boys with high androstenedione levels, directive maternal behavior is associated with physical aggression. The results are subsequently discussed in light of postulates related to parenting characteristic of developmental psychology and we suggest a potential link of our results with the hypothesis of maternal dominance.

The relation of plasma androgen levels to sexual behaviors and attitudes of women.

PubMed

Persky, H; Dreisbach, L; Miller, W R; O'Brien, C P; Khan, M A; Lief, H I; Charney, N; Strauss, D

1982-09-01

Four androgens: dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T), and dihydrotestosterone (DHT), a variety of sexual behaviors and attitudes, and several moods were determined regularly in two groups of healthy, married women who differed by three decades in age. The younger women exhibited significantly higher levels of each androgen, the differences being almost entirely attributable to ovarian failure in the older group. Although the older women reported the same levels of sexual desire and sexual arousal as the younger women, their intercourse frequencies and self-rated sexual gratification scores were significantly lower than the values obtained for the younger wives. One or more of the androgen levels related significantly and in the expected direction to each stage of the four-stage sexual response process. Global measures of so-called "sexual adjustment" and estimates of anxiety, depression, and hostility feelings experienced by these women did not relate significantly to any of the four androgen levels.

Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome.

PubMed

Razavi, M; Jamilian, M; Kashan, Z Fakhrieh; Heidar, Z; Mohseni, M; Ghandi, Y; Bagherian, T; Asemi, Z

2016-03-01

Selenium supplementation could be effective on reproductive outcomes, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS). The aim of the study was to determine the effects of selenium supplementation on reproductive outcomes, biomarkers of inflammation, and oxidative stress in PCOS patients. The present randomized double-blind, placebo-controlled trial was conducted on 64 women aged 18-40 years old with PCOS at the clinic affiliated to Ardabil University of Medical Sciences, Ardabil, Iran. The participants were randomly assigned to 2 groups receiving either 200 μg selenium daily (n=32) or placebo (n=32) for 8 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were measured and compared both before and after the treatment. After 8 weeks of intervention, pregnancy rate in the selenium group was higher than in the placebo group: 18.8 (6/32) vs. 3.1% (1/32), p=0.04. In addition, alopecia (40.6 vs. 9.4%, p=0.004) and acne (46.9 vs. 12.5 %, p=0.003) decreased following the consumption of selenium supplements compared with placebo. Additionally, patients who received selenium supplements had significantly decreased serum dehydroepiandrosterone (DHEA) levels (p=0.02), hirsutism (modified Ferriman-Gallwey scores) (p<0.001), serum high sensitivity C-reactive protein (hs-CRP) (p=0.02), and plasma malondialdehyde (MDA) levels (p=0.01) compared with placebo. We did not observe any significant effects of taking selenium supplements on other hormonal profiles, nitric oxide (NO), and other biomarkers of oxidative stress. Taken together, selenium supplementation for 8 weeks among PCOS women had beneficial effects on reproductive outcomes, DHEA, hs-CRP, and MDA levels. Supporting Information for this article is available online at http://www.thieme-connect.de/products. © Georg Thieme Verlag KG Stuttgart · New York.

Hyperandrogenism in adolescent girls: relationship with the somatotrophic axis.

PubMed

Hernandez, María Isabel; López, Patricia; Gaete, Ximena; Villarroel, Claudio; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Cassorla, Fernando

2017-05-01

During puberty there is a physiologic increase in adrenal and ovarian androgens. It has been suggested that the somatotrophic axis may be related to the development of hyperandrogenism and anovulation in non-obese adult women with polycystic ovarian syndrome (PCOS). The objective of the study was to investigate whether ovarian androgen secretion in young postmenarchal girls is related to the function of their somatotropic axis. This was a cross-sectional study of adolescent girls. We studied non-obese adolescent girls with hyperandrogenism (HA; n = 21) matched with control girls (C; n = 25) for chronological age, age at menarche and body mass index. We obtained a fasting blood sample for measurement of serum glucose, insulin, 17-hydroxyprogesterone (17OH-Prog), dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, sex hormone-binding globulin (SHBG), total testosterone, IGF-I, IGF-II, IGFBP-1, IGFBP-3, ghrelin, leptin, AMH (antiMüllerian hormone), luteinizing hormone (LH) and follicle stimulating hormone (FSH) during the follicular phase of the menstrual period. We performed an oral glucose tolerance test to determine blood glucose, insulin and ghrelin levels and urine samples to measure urinary GH (growth hormone) levels. As expected, the hyperandrogenic girls had significantly higher Ferriman scores, basal total testosterone, free androgen index (FAI), androstenedione, AMH, and basal LH levels compared with the girls in controls. Serum IGF-I, IGF-II, IGFBP-3 and urinary GH did not differ between HA and C. There was a correlation between urinary GH and FAI in all girls (r 0.29, p < 0.05). In addition, in HA girls FAI correlated with insulin, homeostasis model assessment (HOMA) and ghrelin. We observed a correlation between urinary GH and FAI in the hyperandrogenic and control girls, suggesting that the function of the somatotrophic axis may influence the secretion of androgens in adolescent girls.

Multiple latent viruses reactivate in astronauts during Space Shuttle missions.

PubMed

Mehta, S K; Laudenslager, M L; Stowe, R P; Crucian, B E; Sams, C F; Pierson, D L

2014-10-01

Latent virus reactivation and diurnal salivary cortisol and dehydroepiandrosterone were measured prospectively in 17 astronauts (16 male and 1 female) before, during, and after short-duration (12-16 days) Space Shuttle missions. Blood, urine, and saliva samples were collected during each of these phases. Antiviral antibodies and viral load (DNA) were measured for Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and cytomegalovirus (CMV). Three astronauts did not shed any virus in any of their samples collected before, during, or after flight. EBV was shed in the saliva in all of the remaining 14 astronauts during all 3 phases of flight. Seven of the 14 EBV-shedding subjects also shed VZV during and after the flight in their saliva samples, and 8 of 14 EBV-shedders also shed CMV in their urine samples before, during, and after flight. In 6 of 14 crewmembers, all 3 target viruses were shed during one or more flight phases. Both EBV and VZV DNA copies were elevated during the flight phase relative to preflight or post-flight levels. EBV DNA in peripheral blood was increased preflight relative to post-flight. Eighteen healthy controls were also included in the study. Approximately 2-5% of controls shed EBV while none shed VZV or CMV. Salivary cortisol measured preflight and during flight were elevated relative to post-flight. In contrast DHEA decreased during the flight phase relative to both preflight and post-flight. As a consequence, the molar ratio of the area under the diurnal curve of cortisol to DHEA with respect to ground (AUCg) increased significantly during flight. This ratio was unrelated to viral shedding. In summary, three herpes viruses can reactivate individually or in combination during spaceflight. Copyright © 2014 Elsevier Inc. All rights reserved.

Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment.

PubMed

Kushnir, Mark M; Naessén, Tord; Wanggren, Kjell; Hreinsson, Julius; Rockwood, Alan L; Meikle, A Wayne; Bergquist, Jonas

2016-09-01

Steroid concentrations in stimulated follicular fluid (sFF) samples have been linked to the quality of oocytes used in IVF treatments. Most of the published studies focused on evaluating the association of the IVF outcomes with only a few of the steroids, measured by immunoassays (IA). We performed a treatment outcome, prospective cohort study using stimulated FF sampled from 14 infertile women undergoing IVF treatment; single oocyte was used per IVF cycle. Fourteen endogenous steroids were analyzed in 22 ovarian follicle aspirations, which corresponded to the embryos used in the IVF. Ten oocytes were associated with live birth (LB) and 12 with no pregnancy (NP). Steroids were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Differences in distribution of concentrations in association with the pregnancy outcome (LB or NP), and receiver operating characteristic (ROC) curves analysis were performed for the entire cohort and for within-women data. The predominant androgen and estrogen in stimulated sFF were androstenedione (A4) and estradiol (E2), respectively. Lower concentrations of pregnenolone (Pr), lower ratios of A4/ dehydroepiandrosterone (DHEA), testosterone (Te)/DHEA, and greater ratios of E2/Te, and estrone/A4 were observed in sFF samples associated with LB. Among the oocytes associated with NP, in four out of 12 samples total concentration of androgens was above the distribution of the concentrations in the oocytes corresponding to the LB group. Observations of the study indicated increased consumption of precursors and increased biosynthesis of estrogens in the follicles associated with LB. Our data suggest that potentially steroid profiles in sFF obtained during oocyte retrieval may serve as biomarkers for selection of the best embryo to transfer after IVF. Copyright © 2015 Elsevier Ltd. All rights reserved.

Androgen and glucocorticoid production in the male killer whale (Orcinus orca): influence of age, maturity, and environmental factors.

PubMed

O'Brien, J K; Steinman, K J; Fetter, G A; Robeck, T R

2017-01-01

Circulating concentrations of testosterone and its precursor androstenedione, as well as dehydroepiandrosterone (DHEA) and the adrenal hormones cortisol and corticosterone were measured at monthly intervals in 14 male killer whales (Orcinus orca) aged 0.8-38 years. Analyses were performed for examination of the relationships of age, sexual maturation status (STATUS), season, and environmental temperature (monthly air ambient temperature, A-TEMP) with hormone production using a mixed effects linear regression model with animal ID as the random variable. Hormone profiles, derived from enzyme immunoassay procedures validated herein, established that simultaneous up-regulation of androstenedione and testosterone production occurs at puberty, when males are aged 8-12 years. Androgen (testosterone and androstenedione) production in pubertal and adult males was influenced by season, with highest (p < 0.01) concentrations observed in spring and summer months. A significant effect of STATUS and season on DHEA production was also documented, with higher (p < 0.05) concentrations in pubertal and adult males compared to juvenile males, and higher (p < 0.05) concentrations in the months of summer than the fall. Among adult males (≥13 years), those classified as aged (≥31 years) had concentrations of testosterone and both glucocorticoids that were lower (p < 0.05), and those of androstenedione that were higher (p < 0.05) than their younger counterparts. The cortisol:corticosterone ratio for adult males was 7 : 1, and both glucocorticoids were affected by STATUS (p < 0.05), but not season or A-TEMP. Results of this research enhance our understanding of reproductive and adrenocortical function in healthy male killer whales and provide baseline profiles of hormone production for use in the species' health assessment and conservation. © 2016 American Society of Andrology and European Academy of Andrology.

Higher Circulating Leukocytes in Women with PCOS is Reversed by Aerobic Exercise

PubMed Central

Covington, Jeffrey D.; Tam, Charmaine S.; Pasarica, Magdalena; Redman, Leanne M.

2014-01-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, elevated circulating leukocytes, and hypothesized to have higher adipose tissue inflammation. Aerobic exercise reduces circulating leukocytes and improves insulin sensitivity in obese individuals, but the effect of exercise on inflammation in PCOS is not known. We investigated circulating leukocytes, insulin sensitivity by euglycemic-hyperinsulinemic clamp, serum pro- and anti-inflammatory markers (hsCRP, TNF-α, total and high molecular weight adiponectin), and abdominal subcutaneous adipose tissue (SAT) gene expression of proinflammatory markers in 8 PCOS women and 8 obese control females matched for BMI. Additionally, in a prospective study, the 8 women with PCOS underwent a 16-week aerobic exercise regimen with the same measures performed post-intervention. Compared to controls, white blood cell counts (WBC) were 30% higher (p = 0.04) and circulating total adiponectin levels were 150% lower (p = 0.03) in women with PCOS at baseline/pre-exercise conditions. SAT gene expression of macrophage migration inhibitory factor (MIF, p < 0.01) and interleukin-6 (IL-6, p < 0.05) were also lower in women with PCOS. In response to 16 weeks of aerobic exercise, insulin sensitivity improved (p < 0.01) and WBC counts decreased (p = 0.02). The exercise-induced change in WBC and circulating neutrophils correlated inversely with changes in glucose disposal rate (r= -0.73, p=0.03; and r= -0.82, p=0.01, respectively). Aerobic exercise reduced serum leptin (p < 0.05) after 4 weeks, trended to reduce the ratio of leptin-to-high molecular weight adiponectin (p < 0.1) by the 8th week, and significantly increased serum dehydroepiandrosterone sulfate (DHEA-S, p < 0.001) after 16 weeks. In conclusion, women with PCOS have higher circulating leukocytes compared to controls, which can be reversed by aerobic exercise and is associated with improvements in insulin sensitivity. PMID:25446648

The effect of vitamin D supplementation in combination with low-calorie diet on anthropometric indices and androgen hormones in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial.

PubMed

Jafari-Sfidvajani, S; Ahangari, R; Hozoori, M; Mozaffari-Khosravi, H; Fallahzadeh, H; Nadjarzadeh, A

2018-05-01

Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in reproductive age women. The aim of this studywas to evaluate the effects of vitamin D supplementation in combination with low-calorie diet on anthropometric indices, reproductive hormones and menstrual regularity in overweight and obese PCOS women. In this randomized controlled clinical trial, 60 PCOS women with vitamin D insufficiency were randomly assigned to 12 weeks of either (1) weight-loss intervention + 50,000 IU/week oral vitamin D3 or (2) weight-loss intervention + placebo. At the beginning and end of the study, the anthropometric indices, body composition, 25-hydroxyvitamin D, total testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were measured and regularity of menses was compared among the two groups. After 12-week intervention, median of serum 25-hydroxyvitamin D3 significantly increased from 18.5 (10.75-20) ng/ml to 42.69 (34-53.25) ng/ml in vitamin D group compared to placebo group (p < 001). Moreover, there was a significant improvement in frequency regular menstrual cycle (p = 0.01). Mean of weight, body mass index, fat mass, waist and hip circumference and waist-to-hip ratio significantly decreased in both groups, but was not different between two groups. Mean of total testosterone insignificantly decreased from 0.7 to 0.5 ng/ml in vitamin D group (p = 0.18). In addition, we did not observe significant differences regarding DHEAS, FAI and SHBG between two groups. In women with PCOS, androgen profile did not change with vitamin D supplementation when combined with low-calorie diet, but menstrual frequency significantly improved. IRCT2016062710826N19.

Profiling Coping Strategies in Male and Female Rats: Potential neurobehavioral markers of increased resilience to depressive symptoms

PubMed Central

Kent, Molly; Bardi, Massimo; Hazelgrove, Ashley; Sewell, Kaitlyn; Kirk, Emily; Thompson, Brooke; Trexler, Kristen; Terhune-Cotter, Brennan; Lambert, Kelly

2018-01-01

Coping strategies have been associated with differential stress responsivity, perhaps providing a valuable neurobiological marker for susceptibility to the emergence of depressogenic symptoms or vulnerability to other anxiety-related disorders. Rats profiled with a flexible coping phenotype, for example, exhibit increased neurobiological markers of emotional regulation compared to active and passive copers (Bardi et al., 2012; Lambert et al., 2014). In the current study, responses of male and female rats to prediction errors in a spatial foraging task (dry land maze; DLM) were examined after animals were exposed to chronic unpredictable stress (CUS). Brains were processed following the DLM training/assessment for fos-activation patterns and several measures of neuroplasticity in relevant areas. Behavioral responses observed during both the CUS and DLM phases of testing suggested that males and females employ different means of gathering information such as increased ambulatory exploration in males and rear responses in females. Fecal samples collected during baseline and following CUS swim exposure revealed higher corticosterone (CORT) in active copers, whereas flexible copers had higher dehydroepiandrosterone (DHEA) and DHEA/CORT ratios, both indications of enhanced emotional regulation. Focusing on the neural analysis, flexible copers exhibited fewer fos-immunoreactive cells in the basolateral amygdala and a trend toward lower activation in the insula while encountering the prediction error associated with the DLM probe trial. Coping profiles also differentially influenced markers of neuroplasticity; specifically, flexible copers exhibited higher levels nestin-immunoreactivity (ir). Further, less hippocampal glucocorticoid receptor-ir was observed in the flexible copers than the active and passive copers. In sum, flexible coping rats exhibited evidence of emotional resilience as indicated by several neurobiological measures; however, despite increased rates of

Androgen deficiency and dry eye syndrome in the aging male.

PubMed

Azcarate, Patrick M; Venincasa, Vincent D; Feuer, William; Stanczyk, Frank; Schally, Andrew V; Galor, Anat

2014-07-03

To evaluate the relationship between androgen levels and subjective and objective measures of dry eye syndrome (DES). A total of 263 male patients from the Miami Veterans Affairs Medical Center eye clinic aged ≥50 were recruited for this prospective cross-sectional study. Patients completed Dry Eye Questionnaire 5, underwent tear film evaluation, and had serum androgen levels measured. The correlations between androgen levels, DES composite scores, DES symptoms, and global, lipid, and aqueous tear film parameters were evaluated. Two hundred sixty-three patients with a mean age of 69 (50-95) were examined. There was no linear association between composite DES scores (generated using latent class analysis) and androgen levels. However, eyes with high DES scores (0.95-1.0) had higher levels of sex hormone-binding globulin (P = 0.03) and lower levels of dehydroepiandrosterone sulfate (DHEAS) (P = 0.02), androstenedione (A) (P = 0.02), and androstane-3α,17β-diol glucuronide (P = 0.03) compared to eyes with intermediate (0.05-0.95) or low (0-0.05) scores. There were no strong correlations between tear film measures and androgen levels. Regarding global parameters, a weak inverse correlation was found between corneal staining and A (r = -0.17, P = 0.009). For lipid parameters, a weak correlation existed between tear breakup time (TBUT) and A (r = 0.15, P = 0.02). When considering aqueous and lipid deficiency independently, the association between TBUT and A existed only with aqueous tear deficiency (r = 0.66, P = 0.002). Regarding aqueous parameters, a weak correlation existed between Schirmer test and DHEAS (r = 0.13, P = 0.047) and A (r = 0.21, P = 0.001). There was a weak correlation between higher levels of androstenedione and healthier global, lipid, and aqueous tear film parameters. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Effects of combined stress during intense training on cellular immunity, hormones and respiratory infections.

PubMed

Gomez-Merino, Danielle; Drogou, Catherine; Chennaoui, Mounir; Tiollier, Eve; Mathieu, Jacques; Guezennec, Charles Yannick

2005-01-01

This study was designed to determine immune and hormonal changes and their relationship with the incidence of upper respiratory tract infections (URTIs) during an extremely stressful military training (3 weeks of physical conditioning followed by a 5-day combat course with energy restriction, sleep deprivation and psychological stress). Blood samples were collected from 21 cadets (21 +/- 2 years old) before training and after the combat course for analysis of leukocyte and lymphocyte subpopulations, serum cytokines [interleukin-6 (IL-6), IL-1beta and IL-10], and hormones [catecholamines, cortisol, leptin, total insulin-like growth factor I (IGF-I), prolactin, dehydroepiandrosterone sulfate (DHEAS) and testosterone]. Symptoms of URTI were recorded from health logs and medical examinations during training. After the combat course, total leukocyte and neutrophil counts were significantly increased while total lymphocytes were unchanged. In lymphocyte subsets, NK cells were reduced (p < 0.01), while CD4+ and CD19+ (B) cells were increased. Levels of IL-6 were increased (p < 0.01), while those of IL-1beta and IL-10 were unchanged. Norepinephrine and dopamine levels were increased, while those of cortisol were reduced. Levels of leptin, testosterone, prolactin and total IGF-I were reduced, while those of DHEAS were increased. The incidence of URTI increased during the training (chi(2) = 53.48, p < 0.05). After training data analysis showed a significant correlation between URTIs and NK cells (p = 0.0023). Training-induced changes in immune and hormonal parameters were correlated. Blood NK cell levels are related to increased respiratory infections during physical training in a multistressor environment. The training-induced decreases in immunostimulatory hormone levels may have triggered immunosuppression. Copyright (c) 2005 S. Karger AG, Basel.

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

PubMed

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

2014-03-01

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

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

PubMed

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

2012-12-01

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

Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces.

PubMed

Taylor, Marcus K; Carpenter, Jennifer; Stone, Michael; Hernandez, Lisa M; Rauh, Mitchell J; Laurent, Heidemarie K; Granger, Douglas A

2015-11-01

The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic-pituitary-adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high < SS/low = L/high < L/low). Thus, 5HTTLPR and prior trauma exposure demonstrated counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings. Copyright © 2015. Published by Elsevier Inc.

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

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.

Inhibitory effects of Cheongsangbangpoong-tang on both inflammatory acne lesions and facial heat in patients with acne vulgaris: A randomized controlled trial protocol.

PubMed

Kim, Kyuseok; Kim, Kwan-Il; Lee, Junhee

2016-01-22

Due to increasing interest from acne patients concerned about the side effects associated with conventional therapies, complementary and alternative medicine (CAM) has been suggested as a new therapeutic modality for acne vulgaris. Herbal medicine is one of these CAM treatments. Cheongsangbangpoong-tang (CBT) is a common herbal formula used in patients with acne vulgaris in the clinical practice of Korean Medicine (KM). However, despite the common use of CBT in clinical practice, the current level of evidence is insufficient to support an inhibitory effect of CBT on inflammatory acne lesions and facial heat. Therefore, this study was designed to assess the inhibitory effect of CBT on both inflammatory acne lesions and facial heat. A randomized, double-blind, parallel-group, and placebo-controlled trial will be conducted. Fifty-six participants with acne vulgaris will be randomized into one of two groups: the CBT or placebo groups. After randomization, participants will be prescribed either CBT or placebo three times a day at a dose of 5 g after meals for 8 weeks. The following outcome measurements will be used in the examination of subjects: the mean percentage change and the count change of the inflammatory and non-inflammatory acne lesions, the temperature of facial points on digital infrared thermal imaging (DITI), serum cortisol, serum dehydroepiandrosterone-sulfate (DHEA-S), visual analogue scale (VAS), investigator global assessment (IGA), and severity score on the Korean Acne Grading System (KAGS) from baseline to the end of the trial. This trial will provide evidence regarding the inhibitory effect of CBT on inflammatory acne lesions and facial heat. The findings of this trial may have important implications for the more widespread use of CBT for the treatment of acne vulgaris. The trial is registered with the Clinical Research Information Service (CRiS), Republic of Korea: KCT0001468 .

Fetuin-A levels in lean and obese women with polycystic ovary syndrome.

PubMed

Kozakowski, Jarosław; Jeske, Wojciech; Zgliczyński, Wojciech

2014-01-01

The aim of this study was to estimate serum fetuin-A levels in lean and obese women with polycystic ovary syndrome (PCOS) and to find possible relationships between fetuin-A, metabolic factors and androgens in these patients. In 25 lean (18-38 years, BMI 17.5-25.0 kg/m2) and 15 obese women (20-41 years, BMI 28.1-53.2 kg/m2) with PCOS, anthropometric indices and body composition were measured. Fasting serum fetuin-A, adiponectin, leptin, glucose, lipids, hsCRP, insulin, androgens and SHGB levels were estimated. There was no significant difference in serum fetuin-A levels between lean and obese patients: 0.54 ± 0.13 g/L and 0.60 ± 0.14 g/L, respectively. We noted a correlation between BMI and leptin levels (r = 0.88; p < 0.0001) and a nearly significant negative correlation between BMI and adiponectin levels (r = -0.53; p = 0.11) in all subjects. In lean patients, we found a correlation between fetuin-A levels and ALT activity (r = 0.44; p < 0.05). In all participants, fetuin-A correlated directly with DHEA-S levels (r = 0.44; p < 0.03). Serum fetuin-A levels were similar in lean and obese women with PCOS. We found an association between fetuin-A levels and ALT activity in lean patients and between fetuin-A levels and DHEA-S in all women. The role of fetuin-A in the mechanisms of insulin resistance, and its potential impact on androgenic hormones production in women with PCOS, need to be tested in further studies.

Plasma fatty acid ethanolamides are associated with postprandial triglycerides, ApoCIII and ApoE in humans consuming high fructose corn syrup-sweetened beverage.

PubMed

Allister Price, Candice; Argueta, Donovan A; Medici, Valentina; Bremer, Andrew A; Lee, Vivien; Nunez, Marinelle V; Chen, Guoxia X; Keim, Nancy L; Havel, Peter J; Stanhope, Kimber L; DiPatrizio, Nicholas V

2018-04-10

Epidemiological and clinical research studies have provided ample evidence demonstrating that consumption of sugar-sweetened beverages (SSB) increases risk factors involved in the development of obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD). Our previous study demonstrated that when compared to aspartame (Asp), two weeks of high-fructose corn syrup (HFCS)-sweetened beverages provided at 25% of daily energy requirement (Ereq) was associated with increased body weight, postprandial (pp) triglycerides (TG), and fasting and pp CVD risk factors in young adults. The fatty acid ethanolamide, anandamide (AEA), and the monoacylglycerol, 2-arachidonoyl-sn-glycerol (2-AG), are two primary endocannabinoids (ECs) that play a role in regulating food intake, increasing adipose storage, and regulating lipid metabolism. Therefore, we measured plasma concentrations of ECs and their analogs, oleoylethanolamide (OEA), docosahexaenoyl ethanolamide (DHEA), and docosahexaenoyl glycerol (DHG), in participants from our previous study who consumed HFCS- or Asp-sweetened beverages to determine associations with weight gain and CVD risk factors. Two-week exposure to either HFCS- or Asp-sweetened beverages resulted in significant differences in the changes in fasting levels of OEA and DHEA between groups after the testing period. Subjects who consumed Asp, but not HFCS, displayed a reduction in AEA, OEA and DHEA after the testing period. In contrast, there were significant positive relationships between AEA, OEA, and DHEA versus ppTG, ppApoCIII and ppApoE in those consuming HFCS, but not in those consuming Asp. Our findings reveal previously unknown associations between circulating ECs and EC-related molecules with markers of lipid metabolism and CVD risk after HFCS-consumption.

Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6.

PubMed

Cutolo, Maurizio; Straub, Rainer H; Foppiani, Luca; Prete, Camilla; Pulsatelli, Lia; Sulli, Alberto; Boiardi, Luigi; Macchioni, Pierluigi; Giusti, Massimo; Pizzorni, Carmen; Seriolo, Bruno; Salvarani, Carlo

2002-04-01

To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH

In vitro effects of brominated flame retardants and metabolites on CYP17 catalytic activity: A novel mechanism of action?

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

Canton, Rocio F.; Sanderson, J. Thomas; Nijmeijer, Sandra

2006-10-15

Fire incidents have decreased significantly over the last 20 years due, in part, to regulations requiring addition of flame retardants (FRs) to consumer products. Five major classes of brominated flame retardants (BFRs) are hexabromocyclododecane isomers (HBCDs), tetrabromobisphenol-A (TBBPA) and three commercial mixtures of penta-, octa- and deca-polybrominated diphenyl ether (PBDE) congeners, which are used extensively as commercial FR additives. Furthermore, concentrations of PBDEs have been rapidly increasing during the 1999s in human breast milk and a number of endocrine effects have been reported. We used the H295R human adrenocortical carcinoma cell line to assess possible effects of some of thesemore » BFRs (PBDEs and several of their hydroxylated (OH) and methoxylated (CH{sub 3}O) metabolites or analogues), TBBPA and brominated phenols (BPs) on the combined 17{alpha}-hydroxylase and 17,20-lyase activities of CYP17. CYP17 enzyme catalyzes an important step in sex steroidogenesis and is responsible for the biosynthesis of dehydroepiandrosterone (DHEA) and androstenedione in the adrenals. In order to study possible interactions with BFRs, a novel enzymatic method was developed. The precursor substrate of CYP17, pregnenolone, was added to control and exposed H295R cells, and enzymatic production of DHEA was measured using a radioimmunoassay. In order to avoid pregnenolone metabolism via different pathways, specific chemical inhibitor compounds were used. None of the parent/precursor BFRs had a significant effect (P < 0.05) on CYP17 activity except for BDE-183, which showed significant inhibition of CYP17 activity at the highest concentration tested (10 {mu}M), with no signs of cytotoxicity as measured by mitochondrial toxicity tests (MTT). A strong inhibition of CYP17 activity was found for 6-OH-2,2',4,4'-tetrabromoDE (6-OH-BDE47) with a concentration-dependent decrease of almost 90% at 10 {mu}M, but with a concurrent decrease in cell viability at the higher

Profiling intact steroid sulfates and unconjugated steroids in biological fluids by liquid chromatography-tandem mass spectrometry (LC-MS-MS).

PubMed

Galuska, Christina E; Hartmann, Michaela F; Sánchez-Guijo, Alberto; Bakhaus, Katharina; Geyer, Joachim; Schuler, Gerhard; Zimmer, Klaus-Peter; Wudy, Stefan A

2013-07-07

Within the combined DFG research project "Sulfated Steroids in Reproduction" an analytical method was needed for determining sulfated and unconjugated steroids with highest specificity out of different biological matrices such as aqueous solution, cell lysate and serum. With regard to this analytical challenge, LC-MS-MS presents the technique of choice because it permits (1) analysis of the intact steroid conjugate, (2) allows for simultaneous determination of multiple analytes (profiling, targeted metabolomics approach) and (3) is independent of phenomena such as cross-reactivity. Sample work up consisted of incubation of sample with internal standards (deuterium labeled steroids) followed by solid phase extraction. Only serum samples required a protein precipitation step prior to solid phase extraction. The extract was divided in two parts: six steroid sulfates (E1S, E2S, AS, 16-OH-DHEAS, PREGS, DHEAS) were analyzed by C18aQ-ESI-MS-MS in negative ion mode and eleven unconjugated steroids (E3, 16-OH-DHEA, E1, E2, (4)A, DHEA, T, 17-OH-PREG, Prog, An, PREG) were analyzed by C18-APCI-MS-MS in positive ion mode. For steroid sulfates, we found high sensitivities with LoQ values ranging from 0.08 to 1 ng mL(-1). Unconjugated steroids showed LoQ values between 0.5 and 10 ng mL(-1). Calibration plots showed excellent linearity. Mean intra- and inter-assay CVs were 2.4% for steroid sulfates and 6.4% for unconjugated steroids. Accuracy - determined in a two-level spike experiment - showed mean relative errors of 5.9% for steroid sulfates and 6.1% for unconjugated steroids. In summary, we describe a novel LC-MS-MS procedure capable of profiling six steroid sulfates and eleven unconjugated steroids from various biological matrices.

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

The Association between Androgenic Hormone Levels and the Risk of Developing Coronary Artery Disease (CAD).

PubMed

Allameh, Farzad; Pourmand, Gholamreza; Bozorgi, Ali; Nekuie, Sepideh; Namdari, Farshad

2016-01-01

The aim of the study was to evaluate the relationship between the serum levels of androgens and Coronary Artery Disease (CAD) in an Iranian population. Male individuals admitted to Tehran Heart Center and Sina Hospital, Tehran, Iran from 2011-2012 were categorized into CAD and control groups based on selective coronary angiography. Baseline demographic data, including age, BMI, diabetes, and a history of hypertension were recorded. Patients were also assessed for their serum levels of total testosterone, free testosterone, estradiol, dehydroepi and rosterone sulfate (DHEA-S), and Sex Hormone Binding Globulin (SHBG). Data analysis was carried out chi-square and ANOVA tests as well as logistic regression analysis. Two hundred patients were in the CAD group and 135 individuals in control group. In the CAD group, 69 had single-vessel disease, 49 had two-vessel diseases, and 82 had three-vessel diseases. Statistically significant differences were observed between the individuals in the two groups with respect to age (P<0.0001), diabetes (P<0.0001), and a history of hypertension (P=0.018). The serum levels of free testosterone (P=0.048) and DHEA-S (P<0.0001) were significantly higher in the control group than in the CAD group; however, the serum level of SHBG was higher in the CAD group than in the control group (P=0.007). Results of the logistic regression analysis indicated that only age (P=0.042) and diabetes (P=0.003) had significant relationships with CAD. Although the serum levels of some of the androgens were significantly different between the two groups, no association was found between androgenic hormone levels and the risk of CAD, due mainly to the effect of age and diabetes.

The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines.

PubMed

Sandra, Niro; Ester, Pereira; Marie-Agnès, Pélissier; Robert, Morfin; Olivier, Hennebert

2012-04-01

7β-Hydroxy-epiandrosterone (7β-OH-EpiA), an endogenous androgenic derivative of dehydroepiandrosterone, has previously been shown to exert anti-inflammatory action in vitro and in vivo via a shift from prostaglandin E2 (PGE2) to 15-deoxy-Δ(12,14)-PGJ2 production. This modulation in prostaglandin production was obtained with low concentrations of 7β-OH-EpiA (1-100nM) and suggested that it might act through a specific receptor. Inflammation and prostaglandin synthesis is important in the development and survival of estrogen-dependent mammary cancers. Estrogen induced PGE2 production and cell proliferation via its binding to estrogen receptors (ERs) in these tumors. Our objective was to test the effects of 7β-OH-EpiA on the proliferation (by counting with trypan blue exclusion), cell cycle and cell apoptosis (by flow cytometry) of breast cancer cell lines MCF-7 (ERα+, ERβ+, G-protein coupled receptor 30: GPR30+) and MDA-MB-231 (ERα-, ERβ+, GPR30+) and to identify a potential target of this steroid in these cell lineages (by transactivations) and in the nuclear ER-negative SKBr3 cells (GPR30+) (by proliferation assays). 7β-OH-EpiA exerted anti-estrogenic effects in MCF-7 and MDA-MB-231 cells associated with cell proliferation inhibition and cell cycle arrest. Moreover, transactivation and proliferation with ER agonists assays indicated that 7β-OH-EpiA interacted with ERβ. Data from proliferation assays on the MCF-7, MDA-MB-231 and SKBr3 cell lines suggested that 7β-OH-EpiA may also act through the membrane GPR30 receptor. These results support that this androgenic steroid acts as an anti-estrogenic compound. Moreover, this is the first evidence that low doses of androgenic steroid exert antiproliferative effects in these mammary cancer cells. Further investigations are needed to improve understanding of the observed actions of endogenous 7β-OH-EpiA. Copyright © 2012 Elsevier Inc. All rights reserved.

Reconfigurable Carbon Nanotube Multiplexed Sensing Devices.

PubMed

Xu, Xinzhao; Clément, Pierrick; Eklöf-Österberg, Johnas; Kelley-Loughnane, Nancy; Moth-Poulsen, Kasper; Chávez, Jorge L; Palma, Matteo

2018-06-26

Here we report on the fabrication of reconfigurable and solution processable nanoscale biosensors with multisensing capability, based on single-walled carbon nanotubes (SWCNTs). Distinct DNA-wrapped (hence water-soluble) CNTs were immobilized from solution onto different prepatterned electrodes on the same chip, via a low-cost dielectrophoresis (DEP) methodology. The CNTs were functionalized with specific, and different, aptamer sequences that were employed as selective recognition elements for biomarkers indicative of stress and neuro-trauma conditions. Multiplexed detection of three different biomarkers was successfully performed, and real-time detection was achieved in serum down to physiologically relevant concentrations of 50 nM, 10 nM, and 500 pM for cortisol, dehydroepiandrosterone-sulfate (DHEAS), and neuropeptide Y (NPY), respectively. Additionally, the fabricated nanoscale devices were shown to be reconfigurable and reusable via a simple cleaning procedure. The general applicability of the strategy presented, and the facile device fabrication from aqueous solution, hold great potential for the development of the next generation of low power consumption portable diagnostic assays for the simultaneous monitoring of different health parameters.

Callous-unemotional traits and early life stress predict treatment effects on stress and sex hormone functioning in incarcerated male adolescents.

PubMed

Johnson, Megan; Vitacco, Michael J; Shirtcliff, Elizabeth A

2018-03-01

The stress response system is highly plastic, and hormone rhythms may "adaptively calibrate" in response to treatment. This investigation assessed whether stress and sex hormone diurnal rhythms changed over the course of behavioral treatment, and whether callous-unemotional (CU) traits and history of early adversity affected treatment results on diurnal hormone functioning in a sample of 28 incarcerated adolescent males. It was hypothesized that the treatment would have beneficial effects, such that healthier diurnal rhythms would emerge post-treatment. Diurnal cortisol, testosterone, and dehydroepiandrosterone (DHEA) were sampled two weeks after admission to the correctional/treatment facility, and again approximately four months later. Positive treatment effects were detected for the whole sample, such that testosterone dampened across treatment. CU traits predicted a non-optimal hormone response to treatment, potentially indicating biological preparedness to respond to acts of social dominance and aggression. The interaction between CU traits and adversity predicted a promising and sensitized response to treatment including increased cortisol and a steeper testosterone drop across treatment. Results suggest that stress and sex hormones are highly receptive to treatment during this window of development.

Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate: Anabolic, Neuroprotective, and Neuroexcitatory Properties in Military Men

DTIC Science & Technology

2013-01-01

in olfactory bulbectomized mice. J Neurochem 2011; 117(5); 879-91. 14. Gubba EM Fawcett JW, Herbert J; The effects of corticosterone and...Newman AE, MacDougall-Shackleton SA, An YS, Kriengwatana B. Soma KK: Corticosterone and dehydroepiandrosterone have opposing effects on adult...supports nerve cell proliferation), and salivary alpha amylase (sAA; a proxy of sympathetic nervous system function). Separate regression analyses were

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

Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome.

PubMed

Dogan, Bercem Aycicek; Arduc, Ayse; Tuna, Mazhar Muslum; Karakılıc, Ersen; Dagdelen, Iffet; Tutuncu, Yasemin; Berker, Dilek; Guler, Serdar

2014-10-01