MODULATION BY INSULIN OF FOLLICLE-STIMULATING-HORMONE AND LUTEINIZING-HORMONE ACTIONS IN HUMAN GRANULOSA-CELLS OF NORMAL AND POLYCYSTIC OVARIES

Anovulation in polycystic ovary syndrome (PCOS) is associated with hyp erinsulinemia and insulin resistance, but it has been unclear whether the ovary is insulin resistant in women with PCOS. The aims of this st udy were, firstly, to determine whether human granulosa cells respond to physiological concentrations of insulin and, secondly, to investiga te insulin and gonadotropin interactions in vitro in granulosa cells o btained from normal (N) and polycystic ovaries (PCO). Granulosa cells were incubated with insulin with or without gonadotropins for 48 h. In sulin augmented not only basal production of estradiol and progesteron e, but also LH-stimulated steroid accumulation in granulosa cell cultu res from N and PCO. Insulin enhanced FSH-stimulated progesterone produ ction by granulosa cells from N and PCO, but the effect on FSH-stimula ted estradiol production was variable, ranging from no effect for gran ulosa cells from N to synergistic for granulosa cells from PCO of anov ulatory subjects. Preincubation with insulin for 48 h increased subseq uent basal and LH-induced, but not FSH-stimulated, steroid production. These data demonstrate that granulosa cells from PCO respond to insul in despite the association, in vivo, of PCOS with peripheral insulin r esistance. Insulin preincubation enhances the subsequent response of h uman granulosa cells to LH. We propose that in anovulatory women with PCOS, elevated levels of insulin interacting with LH may contribute to the mechanism of anovulation.