Hyperandrogenic origins of polycystic ovary syndrome - implications for pathophysiology and therapy.

Genetic studies, while identifying at least 17 PCOS risk genes, account for <10% of women with PCOS. A number of PCOS risk genes involve regulation of gonadotropin secretion or action, suggesting a reproductive neuroendocrine basis for PCOS pathogenesis. Consistent with this notion, a number of animal models employing fetal androgen excess demonstrate epigenetic induction of PCOS-like traits, including reproductive neuroendocrine and metabolic dysfunction. Monkey models are most comprehensive, while mouse models provide molecular insight, including identifying the androgen receptor, particularly in neurons, as mediating androgen-induced PCOS-like programming. Naturally-occurring female hyperandrogenism is also demonstrated in monkeys. Animal models are poised to delineate molecular gateways to PCOS pathogenesis.