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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.
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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4.
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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5.
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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6.
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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Stroke Risk Factors Unique to Women.
Demel, SL, Kittner, S, Ley, SH, McDermott, M, Rexrode, KM
Stroke. 2018;(3):518-523
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Sex differences, endogenous sex-hormone hormones, sex-hormone binding globulin, and exogenous disruptors in diabetes and related metabolic outcomes.
Liu, S, Sun, Q
Journal of diabetes. 2018;(6):428-441
Abstract
In assessing clinical and pathophysiological development of type 2 diabetes (T2D), the critical role of the sex steroids axis is underappreciated, particularly concerning the sex-specific relationships with many relevant cardiometabolic outcomes. In this issue of the Journal of Diabetes, we provide a comprehensive overview of these significant associations of germline variants in the genes governing the sex steroid pathways, plasma levels of steroid hormones, and sex hormone-binding globulin (SHBG) with T2D risk that have been observed in many clinical and high-quality large prospective cohorts of men and women across ethnic populations. Together, this body of evidence indicates that sex steroids and SHBG should be routinely incorporated into clinical characterization of T2D patients, particularly in screening prediabetic patients, such as those with metabolic syndrome, using plasma levels of SHBG. Given that several germline mutations in the SHBG gene have also been directly related to both plasma concentrations of SHBG and clinical manifestation of T2D, targeting signals in the sex steroid axis, particularly SHBG, may have significant utility in the prediction and treatment of T2D. Further, many of the environmental endocrine disrupting chemicals may exert their potential adverse effects on cardiometabolic outcomes via either estrogenic or androgenic signaling pathways, highlighting the importance of using the sex steroids and SHBG as important biochemical markers in both clinical and population studies in studying sex-specific mechanisms in the pathogenesis of T2D and its complications, as well as the need to equitably allocate resources in studying both men and women.
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9.
The Physiology of Childhood Growth: Hormonal Regulation.
Benyi, E, Sävendahl, L
Hormone research in paediatrics. 2017;(1):6-14
Abstract
The growth patterns of a child changes from uterine life until the end of puberty. Height velocity is highest in utero and declines after birth until puberty when it rises again. Important hormonal regulators of childhood growth are growth hormone, insulin-like growth factor 1, sex steroids, and thyroid hormone. This review gives an overview of these hormonal regulators of growth and their interplay with nutrition and other key players such as inflammatory cytokines.
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10.
Role of neuroinflammation and sex hormones in war-related PTSD.
Mendoza, C, Barreto, GE, Ávila-Rodriguez, M, Echeverria, V
Molecular and cellular endocrinology. 2016;:266-77
Abstract
The susceptibility to develop posttraumatic stress disorder (PTSD) is greatly influenced by both innate and environmental risk factors. One of these factors is gender, with women showing higher incidence of trauma-related mental health disorders than their male counterparts. The evidence so far links these differences in susceptibility or resilience to trauma to the neuroprotective actions of sex hormones in reducing neuroinflammation after severe stress exposure. In this review, we discuss the impact of war-related trauma on the incidence of PTSD in civilian and military populations as well as differences associated to gender in the incidence and recovery from PTSD. In addition, the mutually influencing role of inflammation, genetic, and sex hormones in modulating the consequences derived from exposure to traumatic events are discussed in light of current evidence.