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1.
Steroidogenic Acute Regulatory Protein: Structure, Functioning, and Regulation.
Tugaeva, KV, Sluchanko, NN
Biochemistry. Biokhimiia. 2019;(Suppl 1):S233-S253
Abstract
Steroidogenesis takes place mainly in adrenal and gonadal cells that produce a variety of structurally similar hormones regulating numerous body functions. The rate-limiting stage of steroidogenesis is cholesterol delivery to the inner mitochondrial membrane, where it is converted by cytochrome P450scc into pregnenolone, a common precursor of all steroid hormones. The major role of supplying mitochondria with cholesterol belongs to steroidogenic acute regulatory protein (STARD1). STARD1, which is synthesized de novo as a precursor containing mitochondrial localization sequence and sterol-binding domain, significantly accelerates cholesterol transport and production of pregnenolone. Despite a tremendous interest in STARD1 fueled by its involvement in hereditary diseases and extensive efforts of numerous laboratories worldwide, many aspects of STARD1 structure, functioning, and regulation remain obscure and debatable. This review presents current concepts on the structure of STARD1 and other lipid transfer proteins, the role of STARD1 in steroidogenesis, and the mechanism of its functioning, as well as identifies the most controversial and least studied questions related to the activity of this protein.
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2.
Stress-induced disturbances along the gut microbiota-immune-brain axis and implications for mental health: Does sex matter?
Audet, MC
Frontiers in neuroendocrinology. 2019;:100772
Abstract
Women are roughly twice as likely as men to suffer from stress-related disorders, especially major depression and generalized anxiety. Accumulating evidence suggest that microbes inhabiting the gastrointestinal tract (the gut microbiota) interact with the host brain and may play a key role in the pathogenesis of mental illnesses. Here, the possibility that sexually dimorphic alterations along the gut microbiota-immune-brain axis could play a role in promoting this female bias of mood and anxiety disorders will be discussed. This review will also analyze the idea that gut microbes and sex hormones influence each other, and that this reciprocal crosstalk may come to modulate inflammatory players along the gut microbiota-immune-brain axis and influence behavior in a sex-dependent way.
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3.
Effect of synbiotic pomegranate juice on glycemic, sex hormone profile and anthropometric indices in PCOS: A randomized, triple blind, controlled trial.
Esmaeilinezhad, Z, Babajafari, S, Sohrabi, Z, Eskandari, MH, Amooee, S, Barati-Boldaji, R
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2019;(2):201-208
Abstract
BACKGROUND AND AIMS Polycystic Ovarian Syndrome is a common reproductive, endocrine, and metabolic disease in women. Pomegranate juice, known as a rich source of phytochemicals with high antioxidant activity, enriched with probiotic may improve PCOS. METHODS AND RESULTS A randomized, controlled, triple-blinded, parallel trial study was performed in PCOS patients (n = 92). Three treatment groups (23 patients each) received 2 L of synbiotic pomegranate juice (SPJ), pomegranate juice (PJ), and synbiotic beverage (SB) weekly. The control group (23 patients) received 2 L of placebo beverage weekly. Primary outcome was any change in insulin resistance and secondary outcomes were fasting blood sugar (FBS), insulin sensitivity, testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), body mass index (BMI), waist and hip circumference, from baseline to the end of the trial. At the end of the study, 86 patients were analyzed. There was significant change in insulin resistance in the SPJ and SB groups. Insulin sensitivity increased significantly in the SPJ and SB groups. Insulin also changed significantly in the SPJ and SB groups. BMI, weight and waist circumference decreased significantly in the SPJ and SB groups. Testosterone level also decreased significantly in the SPJ and SB groups. There was no significant change in FPG, LH and FSH in any of the groups. CONCLUSION SPJ in the form of a new beverage can improve insulin resistance, insulin, testosterone level, BMI, weight and waist circumference in PCOS. This trial was registered in Iranian Registry of Clinical Trials, with number: 25272.
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4.
Green Tea Catechin Extract Supplementation Does Not Influence Circulating Sex Hormones and Insulin-Like Growth Factor Axis Proteins in a Randomized Controlled Trial of Postmenopausal Women at High Risk of Breast Cancer.
Samavat, H, Wu, AH, Ursin, G, Torkelson, CJ, Wang, R, Yu, MC, Yee, D, Kurzer, MS, Yuan, JM
The Journal of nutrition. 2019;(4):619-627
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Abstract
BACKGROUND Consumption of green tea has been associated with reduced risk of breast cancer. Hormonal modulation has been suggested as one of the potential underlying mechanisms; however, it has yet to be fully elucidated in large, long-term human clinical trials. OBJECTIVE We investigated the effects of decaffeinated green tea extract (GTE) on circulating sex hormones and insulin-like growth factor (IGF) proteins. METHODS We conducted a placebo-controlled double-blind randomized clinical trial recruiting from 8 clinical centers in Minnesota. Participants were 538 healthy postmenopausal women randomly assigned to the GTE group (463 completed the study; mean age = 60.0 y) and 537 to the placebo group (474 completed; mean age = 59.7 y). Women in the GTE group orally took 4 decaffeinated capsules containing 1315 mg total catechins including 843 mg epigallocatechin-3-gallate daily for 1 y, whereas women in the placebo group took similar capsules containing no tea catechins. Blood sex hormones (estrone, estradiol, androstenedione, testosterone, and sex hormone-binding globulin) and IGF proteins (IGF-1 and IGF binding protein-3) were quantified at baseline and months 6 (for IGF proteins only) and 12, and were assessed as secondary outcomes of the study using a mixed-effect repeated-measures ANOVA model. RESULTS Women in the GTE group had significantly higher blood total estradiol (16%; P = 0.02) and bioavailable estradiol (21%; P = 0.03) than in the placebo group at month 12. There was a statistically significant interaction between GTE supplementation and duration of treatment on estradiol and bioavailable estradiol (both Ps for interaction = 0.001). The catechol-O-methyltransferase genotype did not influence blood sex hormones before or after GTE supplementation. The circulating concentrations of IGF proteins were comparable between GTE and placebo groups at all 3 time points. CONCLUSION These results suggest that a 12-mo GTE supplementation significantly increases circulating estradiol concentrations in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00917735.
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5.
Steroid secretion in healthy aging.
Fiacco, S, Walther, A, Ehlert, U
Psychoneuroendocrinology. 2019;:64-78
Abstract
Nowadays, people spend a considerable amount of their lives as older adults, but this longer lifespan is often accompanied by an increase in chronic conditions and disease, resulting in reduced quality of life and unprecedented societal and economic burden. Healthy aging is therefore increasingly recognized as a healthcare priority. Physical and mental adaptations to changes over the life course, and the maintenance of well-being, represent pivotal challenges in healthy aging. To capture the complexity of healthy aging, we propose a specific phenotype based on body composition, cognition, mood, and sexual function as indicators of different dimensions of healthy aging. With increasing age, sex hormones as well as glucocorticoids undergo significant alterations, and different patterns emerge for women and men. This review describes age-related patterns of change for women and men, and sheds light on the underlying mechanisms. Furthermore, an overview is provided of the challenges for healthy aging resulting from these age-related steroid alterations. While clinical practice guidelines recommend hormonal treatment only in the case of consistently low hormone levels and symptoms of hormone deficiency, physical exercise and a healthy lifestyle emerge as preventive strategies which can counter age-related hormonal changes and at best prevent chronic conditions.
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A decade in female reproduction: an endocrine view of the past and into the future.
Macut, D, Milutinović, DV, Rašić-Marković, A, Nestorov, J, Bjekić-Macut, J, Stanojlović, O
Hormones (Athens, Greece). 2018;(4):497-505
Abstract
Over the last decade, huge achievements have been made in the fields of neurophysiology, molecular endocrinology, and biochemistry, as well as in the successful translation of clinical research into diseases into clinical practice. As regards female reproduction, most of the advances made in this area were achieved in gonadal axis regulation, regulation of behavior through sex steroids, reproductive genetics, preservation of ovarian reproductive function, steroid profiling, and metabolic and overall reproductive outcomes. The coming years are expected to bring further understanding of the relationships between nutrition, energy metabolism, and reproductive function and to succeed in identifying new genetic markers linked to adverse metabolic and unfavorable cardiovascular outcomes in women. From our perspective, future research in the field of female reproduction should be directed toward doing research into genetic reproductive abnormalities and neuroendocrine diseases, pathophysiology, long-term health outcomes for oligo/amenorrhea, hyperandrogenism, and ovulatory dysfunction. It is additionally expected that a better understanding will be gained of the endocrinology of the placenta and of pregnancy, the role of the microbiome in female reproduction, the role of insulin sensitizers, anti-obesity and anti-diabetic drugs, and various advances in the prevention of ovarian damage caused by various oncology therapies, while new therapeutic options for the treatment of infertility, including kisspeptin, will be developed.
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Regulation of sex hormone receptors in sexual dimorphism of human cancers.
Zheng, D, Williams, C, Vold, JA, Nguyen, JH, Harnois, DM, Bagaria, SP, McLaughlin, SA, Li, Z
Cancer letters. 2018;:24-31
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Abstract
Gender differences in the incidences of cancers have been found in almost all human cancers. However, the mechanisms that underlie gender disparities in most human cancer types have been under-investigated. Here, we provide a comprehensive overview of potential mechanisms underlying sexual dimorphism of each cancer regarding sex hormone signaling. Fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of precision medicine. Our discussions of potential mechanisms underlying sexual dimorphism in each cancer will be instructive for future cancer research on gender disparities.
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Targeting hypothalamic-pituitary-adrenal axis hormones and sex steroids for improving cognition in major mood disorders and schizophrenia: a systematic review and narrative synthesis.
Soria, V, González-Rodríguez, A, Huerta-Ramos, E, Usall, J, Cobo, J, Bioque, M, Barbero, JD, García-Rizo, C, Tost, M, Monreal, JA, et al
Psychoneuroendocrinology. 2018;:8-19
Abstract
Cognitive deficits are a core feature of serious mental illnesses such as schizophrenia, major depressive disorder (MDD) and bipolar disorder (BD) and are a common cause of functional disability. There is limited efficacy of pharmacological interventions for improving the cognitive deficits in these disorders. As pro-cognitive pharmacological treatments are lacking, hormones or drugs that target the endocrine system may become potential candidates for 'repurposing' trials aiming to improve cognition. We aimed to study whether treatment with drugs targeting the hypothalamic-pituitary-adrenal (HPA) axis and sex steroids can improve cognition in patients with schizophrenia, MDD or BD. A systematic search was performed using PubMed (Medline), PsychInfo and clinicaltrials.gov, and a narrative synthesis was included. The systematic review identified 12 studies dealing with HPA-related drugs (mifepristone [n = 3], cortisol synthesis inhibitors [ketoconazole, n = 2], dehydroepiandrosterone [n = 5], fludrocortisone [n = 2]) and 14 studies dealing with sex steroids (oestradiol [n = 2], selective oestrogen receptor modulators [raloxifene, n = 7], pregnenolone [n = 5]). Positive trials were found for BD (mifepristone), MDD (dehydroepiandrosterone and fludrocortisone) and schizophrenia (dehydroepiandrosterone, raloxifene and pregnenolone). A replication of positive findings by at least two clinical trials was found for mifepristone in BD and raloxifene and pregnenolone in schizophrenia. The use of drugs targeting hormones related to the HPA axis and sex steroids is a promising field of research that might help to improve the cognitive outcome of patients with schizophrenia, bipolar disorder and major depressive disorder in the near future.
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Effect of exercise and/or reduced calorie dietary interventions on breast cancer-related endogenous sex hormones in healthy postmenopausal women.
de Roon, M, May, AM, McTiernan, A, Scholten, RJPM, Peeters, PHM, Friedenreich, CM, Monninkhof, EM
Breast cancer research : BCR. 2018;(1):81
Abstract
BACKGROUND Physical inactivity and being overweight are modifiable lifestyle risk factors that consistently have been associated with a higher risk of postmenopausal breast cancer in observational studies. One biologic hypothesis underlying this relationship may be via endogenous sex hormone levels. It is unclear if changes in dietary intake, physical activity, or both, are most effective in changing these hormone levels. OBJECTIVE This systematic review and meta-analysis examines the effect of reduced caloric dietary intake and/or increased exercise levels on breast cancer-related endogenous sex hormones. METHODS We conducted a systematic literature search in MEDLINE, Embase, and Cochrane's Central Register of Controlled Trials (CENTRAL) up to March 2017. Main outcome measures were breast cancer-related endogenous sex hormones. Randomized controlled trials (RCTs) reporting effects of reduced caloric intake and/or exercise interventions on endogenous sex hormones in healthy, physically inactive postmenopausal women were included. Studies including women using hormone therapy were excluded. The methodological quality of each study was assessed by the Cochrane's risk of bias tool. RESULTS From the 2599 articles retrieved, seven articles from six RCTs were included in this meta-analysis. These trials investigated 1588 healthy postmenopausal women with a mean age ranging from 58 to 61 years. A combined intervention of reduced caloric intake and exercise, with durations ranging from 16 to 52 weeks, compared with a control group (without an intervention to achieve weight loss) resulted in the largest beneficial effects on estrone treatment effect ratio (TER) = 0.90 (95% confidence interval (CI) = 0.83-0.97), total estradiol TER = 0.82 (0.75-0.90), free estradiol TER = 0.73 (0.66-0.81), free testosterone TER = 0.86 (0.79-0.93), and sex hormone biding globulin (SHBG) TER = 1.23 (1.15-1.31). A reduced caloric intake without an exercise intervention resulted in significant effects compared with control on total estradiol TER = 0.86 (0.77-0.95), free estradiol TER = 0.77 (0.69-0.84), free testosterone TER = 0.91 (0.84-0.98), and SHBG TER = 1.20 (1.06-1.36). Exercise without dietary change, versus control, resulted in borderline significant effects on androstenedione TER = 0.97 (0.94-1.00), total estradiol TER = 0. 97 (0.94-1.00), and free testosterone TER = 0. 0.97 (0.95-1.00). CONCLUSIONS AND RELEVANCE This meta-analysis of six RCTs demonstrated that there are beneficial effects of exercise, reduced caloric dietary intake or, preferably, a combination of exercise and diet on breast cancer-related endogenous sex hormones in physically inactive postmenopausal women.
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Circulating steroid levels as correlates of adipose tissue phenotype in premenopausal women.
Marchand, GB, Carreau, AM, Laforest, S, Côté, JA, Daris, M, Cianflone, K, Prehn, C, Adamski, J, Tchernof, A
Hormone molecular biology and clinical investigation. 2018;(1)
Abstract
Background Obesity-related alterations in the circulating steroid hormone profile remain equivocal in women. Our objective was to identify circulating steroid levels that relate to increased adiposity and altered adipose phenotype in premenopausal women. Materials and methods In a sample of 42 premenopausal women [age 46 ± 3 years; body mass index (BMI) 27.1 ± 4.2 kg/m2], 19 plasma steroids were quantified by electrospray ionization-liquid chromatography-tandem mass spectroscopy (ESI-LC-MS/MS). Body composition and fat distribution were assessed by dual-energy X-ray absorptiometry (DXA) and computed tomography (CT), respectively. Markers of adipose tissue function including adipocyte size distributions, radiological attenuation and macrophage infiltration were also analyzed in surgically obtained visceral and subcutaneous fat samples. Results Many negative correlations were observed between adiposity measurements such as BMI, body fat percentage or total abdominal adipose tissue area and plasma levels of androstenedione (Δ4) (r = -0.33 to -0.39, p ≤ 0.04), androsterone (ADT) (r = -0.30 to -0.38, p ≤ 0.05) and steroid precursor pregnenolone (PREG) (r = -0.36 to -0.46, p ≤ 0.02). Visceral adipocyte hypertrophy was observed in patients with low PREG concentrations (p < 0.05). Visceral adipose tissue radiologic attenuation, a potential marker of adipocyte size, was also positively correlated with PREG levels (r = 0.33, p < 0.05). Low levels of PREG were related to increased number of macrophages infiltrating visceral and subcutaneous adipose tissue (p < 0.05). Conclusion Plasma levels of androgens and their precursors are lower in women with increased adiposity and visceral adipocyte hypertrophy. Low circulating PREG concentration may represent a marker of adipose tissue dysfunction.