Anovulation in
polycystic ovary syndrome (PCOS) is associated with
hyperinsulinemia and
insulin resistance, but it has been unclear whether the ovary is
insulin resistant in women with PCOS. The aims of this study were, firstly, to determine whether human granulosa cells respond to physiological concentrations of
insulin and, secondly, to investigate
insulin and
gonadotropin interactions in vitro in granulosa cells obtained from normal (N) and polycystic ovaries (PCO). Granulosa cells were incubated with
insulin with or without
gonadotropins for 48 h.
Insulin augmented not only basal production of
estradiol and
progesterone, but also LH-stimulated
steroid accumulation in granulosa cell cultures from N and PCO.
Insulin enhanced FSH-stimulated
progesterone production by granulosa cells from N and PCO, but the effect on FSH-stimulated
estradiol production was variable, ranging from no effect for granulosa cells from N to synergistic for granulosa cells from PCO of anovulatory subjects. Preincubation with
insulin for 48 h increased subsequent basal and LH-induced, but not FSH-stimulated,
steroid production. These data demonstrate that granulosa cells from PCO respond to
insulin despite the association, in vivo, of PCOS with peripheral
insulin resistance.
Insulin preincubation enhances the subsequent response of human 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.