THE INSULIN-LIKE GROWTH-FACTOR SYSTEM IN NORMAL AND ABNORMAL HUMAN OVARIAN FOLLICLE DEVELOPMENT

Intraovarian peptides synergize with and potentiate gonadotropin actio ns in ovarian follicular development. The insulin-like growth factor s ystem is one of several growth factor systems that regulate a variety of processes in ovarian granulosa and theca cells. Insulinlike growth factor binding proteins, which generally inhibit insulin-like growth f actor action, are high in androgen-dominant but not estrogen-dominant follicles, and these insulin-like growth factor binding proteins may l imit the co-gonadotropic actions of insulinlike 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 a re normal and yet there is an accumulation of androstenedione substrat e. Aromatase activity can be activated when granulosa are isolated fro m the polycystic ovary syndrome follicle but is not active in the foll icle in situ. High levels of insulin-like growth factor binding protei ns are present and likely inhibit insulin-like growth factor action in this arrested stage of development. Whether they contribute to it dir ectly or reflect the androgen-dominant state of the follicle is not kn own at this time. Insulin resistance in polycystic ovary syndrome may result from insulin acting on surrogate receptors, like the insulin-li ke growth factor receptor, although the precise roles of insulin and t he insulin-like growth factor system in the pathogenesis of polycystic ovary syndrome and associated states of hyperandrogenism remain to be defined.