Androgens stimulate early stages of follicular growth in the primate ovary

Abstract

The concept that androgens are atretogenic, derived from murine ovary studies, is difficult to reconcile with the fact that hyperandrogenic women have more developing follicles than normal-cycling women. To evaluate androgen's effects on primate follicular growth and survival, normal-cycling rhesus monkeys were treated with placebo-, testosterone-(T), or dihydrotestosterone-sustained release implants, and ovaries were taken for histological analysis after 3-10 d of treatment. Growing preantral and small antral follicles up to 1 mm in diameter were significantly and progressively increased in number and thecal layer thickness in T-treated monkeys from 3-10 d. Granulosa and thecal cell proliferation, as determined by immunodetection of the Ki67 antigen, were significantly increased in these follicles. Preovulatory follicles (> 1 mm), however, were not increased in number in androgen-treated animals. Follicular atresia was not increased and there were actually significantly fewer apoptotic granulosa cells in the T-treated groups. Dihydrotestosterone treatment had identical effects, indicating that these growth-promoting actions are mediated by the androgen receptor. These findings show that, over the short term at least, androgens are not atretogenic and actually enhance follicular growth and survival in the primate. These new data provide a plausible explanation for the pathogenesis of "polycystic" ovaries in hyperandrogenism.