The prenatally androgenized female rhesus monkey as a model for polycystic ovary syndrome

Studies contained within this thesis examined reproductive and metabolic consequences of prenatal androgen excess in adult female rhesus monkeys in order to test the hypothesis that prenatal androgen excess is the core developmental defect leading to polycystic ovary syndrome (PCOS) in women. The first study determined whether prenatal androgen excess results in ovulatory dysfunction in adult female rhesus monkeys, by measuring serum progesterone concentrations from twice-weekly blood samples obtained over 90 days. Prenatal androgen excess conferred a greater incidence of oligoovulation that was further enhanced by adiposity. Furthermore, luteal phase lengths from ovulatory cycles in prenatally androgenized females were shorter than those in controls, suggesting impaired luteal function.; The second study examined whether there was an ovarian thecal cell component to the hyperandrogenism exhibited by adult prenatally androgenized female rhesus monkeys by measuring the steroid response to a recombinant human chorionic gonadotropin (rhCG) challenge. Prenatally androgenized females exhibited an enhanced testosterone and 17α-hydroxyprogesterone response to rhCG compared to control females, suggesting ovarian hyperandrogenism. Increased serum dehydroepiandrosterone concentrations, independent of rhCG, in prenatally androgenized females suggested an adrenal component to the hyperandrogenism.; The third study examined insulin action and secretion in prenatally androgenized female rhesus monkeys using intravenous glucose tolerance testing. Androgen excess starting during early gestation impaired pancreatic β-cell function, and androgen excess starting during late gestation conferred increased sensitivity to insulin, which was negatively impacted by adiposity. The final study determined whether prenatal androgen excess during early gestation alters body fat distribution by using dual x-ray absorptiometry and computed tomography. Body fat mass was similar between prenatally androgenized and control females matched for age, body weight and BMI, however total abdominal and visceral fat mass were increased in prenatally androgenized females. Androgen excess during early gestation enhances the preferential accumulation of abdominal adiposity in these females and may contribute to their altered insulin action and secretion. These studies contributed to the establishment of the prenatally androgenized female rhesus monkey as an animal model for studying PCOS, allowing further investigation into development and pathogenesis of the syndrome, and systematic studies into its progression from prenatal life through menopause.