The insulin-like growth factor system in normal and abnormal human ovarian follicle development.

Intraovarian peptides synergize with and potentiate gonadotropin actions in ovarian follicular development. The insulin-like growth factor system is one of several growth factor systems that regulate a variety of processes in ovarian granulosa and theca cells. Insulin-like growth factor binding proteins, which generally inhibit insulin-like growth factor action, are high in androgen-dominant but not estrogen-dominant follicles, and these insulin-like growth factor binding proteins may limit the co-gonadotropic actions of insulin-like growth factors within the follicle. Evidence is accumulating that insulin-like growth factor binding proteins within estrogen-dominant follicles are regulated by decreased production and by increased degradation. In polycystic ovary syndrome, in which follicles are at an arrested stage of maturation, insulin-like growth factor I and follicle stimulating hormone levels are normal and yet there is an accumulation of androstenedione substrate. Aromatase activity can be activated when granulosa are isolated from the polycystic ovary syndrome follicle but is not active in the follicle in situ. High levels of insulin-like growth factor binding proteins are present and likely inhibit insulin-like growth factor action in this arrested stage of development. Whether they contribute to it directly or reflect the androgen-dominant state of the follicle is not known at this time. Insulin resistance in polycystic ovary syndrome may result from insulin acting on surrogate receptors, like the insulin-like growth factor receptor, although the precise roles of insulin and the insulin-like growth factor system in the pathogenesis of polycystic ovary syndrome and associated states of hyperandrogenism remain to be defined.