Perinatal androgen exposure and adipose tissue programming: Is there an impact on body weight fate?

© 2015 Informa UK, Ltd. Obesity is a major concern in public health because it is one of the main risk factors for the development of non-transmissible chronic diseases. The fact that there is a clear sex dimorphism in normal body fat distribution points out the role of sex steroids as key factors in the regulation and function of the adipose cell. Androgens affect adipogenesis and fat metabolism in the adipose tissue of males and females. Hormonal disorders during pregnancy may affect the fetal tissues, with long-term implications leading to the development of pathologies during adult life. Obesity and metabolic disease are among these. In this regard, animal models have demonstrated an abnormal fat distribution and modifications in the size and function of adipose cells in the female and male offspring of mothers exposed to androgen excess during pregnancy

Metabolic Features Across the Female Life Span in Women with PCOS

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine metabolic disorder and is presently considered a family pathology. It is associated with obesity, insulin resistance and metabolic syndrome. Racial, ethnic and environmental factors may be important in determining the clinical manifestations of this syndrome. Polycystic ovary syndrome is an exclusion diagnosis and, therefore, should be distinguished from the physiological changes typical for the age and from other hyperandrogenic disorders. Early diagnosis is important since this syndrome is associated with reproductive, oncologic and metabolic risks. Interestingly, the clinical features of this disorder may change throughout the lifespan of a PCOS woman, starting from adolescence to postmenopausal age. During the first decades of life the main features are in the reproductive area, while later in life metabolic abnormalities are more evident. While the assessment of insulin resistance is not part of the diagnosis of PCOS, it has been demonstrated that this metabolic component appears early in life and persists over time. Moreover during puberty and pregnancy, insulin resistance is exacerbated. Pregnancy represents an important stage, as the offspring of these patients may be reprogrammed and inherit some of the metabolic and reproductive features of their mothers. In the present review, we will focus on several metabolic aspects of the PCOS condition at different stages of life in a Chilean populationFondo Nacional de Desarrollo Cientifico y Tecnologico (National Fund for Scientific and Technological Research) Fondecyt 1970291 1030487 1050915 1071007 1110864 1151531 SOCHED (Chilean Society of Endocrinology and Diabetes) 2009-48 05 Alexander von Humboldt Foundatio

Obesity during pregnancy affects sex steroid concentrations depending on fetal gender

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Background/Objective:It is not clear whether maternal obesity along with fetal gender affect sex steroid metabolism during pregnancy. Therefore, we compared sex steroid concentrations and placental expression of steroidogenic enzymes between non-obese and obese pregnant women with non-pathological pregnancies, and investigated the influence of fetal gender on these parameters.Methods:In 35 normal weight (body mass index (BMI) 20-24.9 kg m - 2) (controls) and 36 obese women (BMI 30-36 kg m - 2) (obese), a fasting blood sample was obtained at first and at third trimester of gestation to measure progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione, testosterone and estradiol by liquid chromatography-tandem mass spectrometry and estrone by radioimmunoassay. In a subset of women, placental mRNA and protein expression of steroidogenic enzymes was measured by quantitative PCR and western

Testosterone increases CCL-2 expression in visceral adipose tissue from obese women of reproductive age

© 2017 Elsevier B.V. Context Hyperandrogenic states and obesity in women are associated with insulin-resistance. Androgens reduce glucose uptake in adipose cells and increase TNFα production in peripheral monocytes. Inflammatory cytokines have a known detrimental effect on insulin resistance. The aim of the present study was to explore the role of testosterone in local cytokine production in visceral adipose tissue from women of reproductive age. Design Twenty-four women 18–40 years old, undergoing elective abdominal surgery for benign and non-inflammatory conditions, were recruited for the study. Women with clinical hyperandrogenism, diabetes, hepatic or renal dysfunction, hypothyroidism, BMI> 40 or drugs known to interfere with hormonal levels or fat metabolism were excluded. Women were classified into two groups according to BMI, non-obese (N–O; BMI < 30) and obese (O; BMI 30–40). A basal blood sample was drawn at the time of surgery for the measurement of glucose, insulin, total t

Testosterone-induced downregulation of anti-Mü llerian hormone expression in granulosa cells from small bovine follicles

Polycystic ovary syndrome (PCOS) is characterized by the presence of hyperandrogenism and an increased follicular mass probably determined by deregulation of locally produced factors. Anti-Müllerian hormone (AMH) is a glycoprotein that inhibits follicular recruitment and determines the size of the follicular pool. To evaluate the role of androgens in the regulation of AMH expression in bovine granulosa cells from small follicles, granulosa cells from 3 to 4 mm follicles were isolated and incubated in basal culture media, or in media containing testosterone (T) at 10-5M, T 10-8M, or estradiol (E2) at 150 ng/ml for 48 h. AMH mRNA levels of these cells were determined using real-time PCR (RT PCR). AMH protein levels and E 2 were determined in cell-conditioned media. A 3.4-fold decrease in AMH mRNA levels was observed in granulosa cells exposed to T 10-5M (P = 0.03, n = 5), but not in cells exposed to T 10-8M. AMH protein levels showed a 1.8-fold reduction in cell-conditioned media from c

Effects of pregnancy and changes in body weight on polycystic ovary syndrome phenotypesaccording to the Rotterdam criteria Clasificación de los fenotipos de síndrome de ovario poliquístico de acuerdo a los criterios de Rotterdam: ¿una condición estática o

© 2014, Sociedad Medica de Santiago. All rights reserved. Background: Polycystic Ovary Syndrome (PCOS) is tightly associated with insulin resistance and obesity and characterized by hyperandrogenism, chronic oligo-anovulation and polycystic ovarian morphology when fully expressed. The 2003 Rotterdam consensus proposed that two or three of these features were necessary to make the diagnosis, which generated four phenotypes. Several studies have suggested that these phenotypes could differ in their metabolic and endocrine characteristics and that they could vary in the same patient when analyzed throughout life. Aim: To determine if the initial classification of PCOS phenotypes is modified by different physiological conditions. Material and Methods: We performed a non-concurrent prospective analysis of 88 women with PCOS according to the Rotterdam criteria. The effect of physiological conditions such as changes in body weight, pregnancy and ageing more than five years on PCOS phenotype

CAG repeat polymorphism of androgen receptor gene and X-chromosome inactivation in daughters of women with polycystic ovary syndrome (PCOS): Relationship with endocrine and metabolic parameters

Background: The polycystic ovary syndrome (PCOS) is a hyperandrogenic disorder that arise from a combination of genetic and environmental factors. Aim: To assess the role of the androgen receptor (AR) CAG repeat polymorphism in the metabolic and reproductive features in daughters of women with PCOS (PCOSd). Methods: Sixty-seven PCOSd and 60 daughters of control women (Cd) were studied in early stages of sexual development. Sex steroids, glucose, insulin and lipids were determined. The AR CAG repeat sizes and X-chromosome inactivation (XCI) were analyzed. Results: PCOSd and Cd had similar mean number of CAG repeats and XCI pattern. In PCOSd and Cd, methylation-weighted biallelic means CAGn (mwCAGn) was not associated with androgen levels. In infants and pubertal PCOSd, mwCAGn was associated with a low concentration of HDL-cholesterol. Conclusions: AR CAG repeat polymorphism appears to be unrelated with serum androgen levels. However, the short mwCAGn variant may have a possible impact

Enlarged adipocytes in subcutaneous adipose tissue associated to hyperandrogenism and visceral adipose tissue volume in women with polycystic ovary syndrome

Context Polycystic ovary syndrome (PCOS) is an androgen excess disorder associated with obesity and adipose tissue disturbances. Our aim was to evaluate gene expression of adipocytokines and adipocyte characteristics in abdominal subcutaneous adipose tissue (SAT) of PCOS women. Design: Twelve PCOS (PCOSw) and 12 control (Cw) premenopausal women (BMI 20-35 kg/m(2)) were included, with measurements of whole-body composition assessed by dual-energy X-ray absorptiometry, and abdominal subcutaneous and visceral adipose tissue (VAT) volume, by magnetic resonance imaging. An oral glucose tolerance test was performed with measurements of glucose and insulin, and sex steroids, lipid profile and serum adipocytokines were determined in the fasting sample. Adipocytokine gene expression, mean adipocyte area and macrophage infiltration were evaluated in SAT biopsies. Results: Both groups were comparable in, age and BMI. Trunk fat mass amount (p = .043), serum and SAT leptin/adiponectin ratio (p = .034 and p = .028, respectively) and adipocyte area (p = .015) were higher in PCOSw compared to Cw. Interestingly, trunk fat mass was positively correlated with adipocyte area in PCOSw (r = 0.821, p = .028), while the inverse correlation was found in. Cw (r = -0.786, p = .021). Only in PCOSw, adipocyte area was positively correlated with serum testosterone (r = 0.857, p = .014) and visceral adipose tissue volume (r = 0.857, p = .014). Conclusions: Our results indicate that PCOS women present adipose tissue dysfunction in the subcutaneous compartment, characterized by an alteration in adipocyte size and leptin/adiponectin expression and secretion, probably associated with higher androgen concentrations.Fondo Nacional de Desarrollo Cientifico y Tecnologico (National Fund for Scientific and Technological Research) 1110864 115153

Adrenal function during childhood and puberty in daughters of women with polycystic ovary syndrome

Context: In some patients, PCOS may develop as a consequence of an exaggerated adrenarche during pubertal development. Objective: The aim of the study was to assess adrenal function during childhood and pubertal development in daughters of women with PCOS (PCOSd). Design: We included 98 PCOSd [64 during childhood (ages 4-8 yr) and 34 during the peripubertal period (ages 9-13 yr)] and 51 daughters of controlwomen(Cd) [30 during childhood and 21 during the peripubertal period]. In both groups, an acute ACTH-(1-24) stimulation test (0.25 mg) and an oral glucose tolerance test were performed. Bone age and serum concentrations of cortisol, androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), glucose, and insulin were determined. Results: PCOSd and Cd were similar in age and body mass index. During the peripubertal period, basal and poststimulated DHEAS concentrations were higher in PCOSd compared to Cd. Among PCOSd, 12.5% of girls in childhood and 3

Early metabolic derangements in daughters of women with polycystic ovary syndrome

Context: Polycystic ovary syndrome (PCOS) is a familial endocrine-metabolic dysfunction, increasingly recognized in adolescent girls with hyperandrogenism. However, it is difficult to establish whether the metabolic abnormalities described in PCOS are present before the onset of hyperandrogenism. In children, a strong association of adiponectin levels with metabolic parameters of insulin resistance has been described. Objective: The objective of the study was to evaluate adiponectin serum concentrations and metabolic parameters in prepubertal and pubertal daughters of women with PCOS to identify girls with increased metabolic risk. Design: Fifty-three prepubertal and 22 pubertal (Tanner stages II-V) daughters of PCOS women (PCOSd) and 32 prepubertal and 17 pubertal daughters of control women (Cd) were studied. In both groups, an oral glucose tolerance test was performed with measurement of glucose and insulin. Adiponectin, leptin, C-reactive protein, SHBG, sex steroids, and lipids wer