Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome

• Published in: International Journal of Obesity Vol. 31; no. 10; pp. 1579 - 1585
• Main Authors: Bruns, C.M, Baum, S.T, Colman, R.J, Dumesic, D.A, Eisner, J.R, Jensen, M.D, Whigham, L.D, Abbott, D.H
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01-10-2007; Nature Publishing Group
• Subjects: Abdomen; Absorptiometry, Photon; Androgens; Androgens - administration & dosage; Androgens - adverse effects; animal models; Animals; Biological and medical sciences; blood chemistry; Body composition; Body Composition - drug effects; Body Composition - physiology; body conformation; Body fat; Body Fat Distribution; Body mass index; Case-Control Studies; Computed tomography; Diabetes; Exposure; Feeding. Feeding behavior; Female; Female genital diseases; Females; Fundamental and applied biological sciences. Psychology; Genetic aspects; glucose tolerance; Glucose Tolerance Test - methods; Gynecology. Andrology. Obstetrics; Health aspects; Heterogeneity; insulin; Insulin Resistance; Laboratory animals; Macaca mulatta; Measurement; Medical sciences; Metabolic diseases; Metabolism; Monkeys & apes; Non tumoral diseases; Obesity; ovarian cysts; Ovaries; Polycystic ovary syndrome; Polycystic Ovary Syndrome - complications; Pregnancy; prenatal development; Prenatal Exposure Delayed Effects; Research centers; Risk factors; somatometrics; Stein-Leventhal syndrome; Testosterone; Tomography; Tomography, X-Ray Computed; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; visceral fat; United States; United States > US; Endocrinopathy; Type 2 diabetes; Pancreatic hormone; Adipose tissue; Polycystic ovary; Fat mass; Body composition; polycystic ovary syndrome; Prenatal; Cyst; Primates; Testicular hormone; Benign neoplasm; Nutritional status; Obesity; Androgen; Nutrition; Nonhuman primate; Nutrition disorder; Female sterility; Metabolic diseases; Insulin; Female genital diseases; Ovarian diseases; Target tissue resistance; Testosterone; Vertebrata; Mammalia; Distribution; Insulin resistance; Sex steroid hormone
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0803638

Introduction: Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in common with polycystic ovary syndrome (PCOS) women. Early gestation exposure (E) results in insulin resistance, impaired pancreatic beta-cell function and type 2 diabetes, while late gestation exposure (L) results in supranormal insulin sensitivity that declines with increasing body mass index (BMI). Objective: To determine whether PA females have altered body fat distribution. Design: Five early-treated PA (EPA), five late-treated PA (LPA) and five control adult female monkeys underwent somatometrics, dual-X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Five control and five EPA females underwent an intravenous glucose tolerance test to assess the relationship between body composition and glucoregulation. Results: There were no differences in age, weight, BMI or somatometrics. LPA females had approximately 20% greater DXA-determined total fat and percent body fat, as well as total and percent abdominal fat than EPA or control females (P less than or equal to 0.05). LPA females also had approximately 40% more CT-determined non-visceral abdominal fat than EPA or control females (P less than or equal to 0.05). The volume of visceral fat was similar among the three groups. EPA (R2=0.94, P less than or equal to 0.01) and LPA (R2=0.53, P=0.16) females had a positive relationship between visceral fat and BMI, although not significant for LPA females. Conversely, control females had a positive relationship between non-visceral fat and BMI (R2=0.98, P less than or equal to 0.001). There was a positive relationship between basal insulin and total body (R2=0.95, P less than or equal to 0.007), total abdominal (R2=0.81, P less than or equal to 0.04) and visceral (R2=0.82, P less than or equal to 0.03) fat quantities in EPA, but not control females. Conclusions: Prenatal androgenization in female rhesus monkeys induces adiposity-dependent visceral fat accumulation, and late gestation androgenization causes increased total body and non-visceral fat mass. Early gestation androgenization induces visceral fat-dependent hyperinsulinemia. The relationship between the timing of prenatal androgen exposure and body composition phenotypes in this nonhuman primate model for PCOS may provide insight into the heterogeneity of metabolic defects found in PCOS women.