DEVELOPMENTALLY-REGULATED RESPONSES OF HUMAN GRANULOSA-CELLS TO INSULIN-LIKE GROWTH-FACTORS (IGFS) - IGF-I AND IGF-II ACTION MEDIATED VIA THE TYPE-I IGF RECEPTOR

In experimental animal models, insulin-like growth factors (IGFs) have been found to be more potent stimulators of ovarian function than ins ulin. In human theca cells, however, insulin, IGF-I, and IGF-II have s imilar effects on androgen production. The relative effects of insulin and IGFs on human granulosa cell. steroidogenesis is unknown. Further more, it is unclear whether effects of IGF-II on steroidogenesis are m ediated by the type-I or type-Il IGF receptor. The effects of insulin, IGF-I, and IGF-II on human granulosa cell steroidogenesis mere compar ed in vitro. As expected, insulin, IGF-I, and IGF-II enhanced steroido genesis. Previously, IGF-II has been shown to enhance granulosa cell s teroid production after insulin pre-incubation. In this study, an effe ct of IGF-II, independent of insulin priming, also was observed. In gr anulosa cell cultures from small antral follicles (less than or equal to 13 mm), insulin and IGF-I stimulated steroid production to a simila r degree, whereas IGF-II was less effective. In contrast, IGFs were mo re effective than insulin (IGF-I > IGF-II > insulin) in granulosa cell s isolated from preovulatory follicles. IGF-I and IGF-II actions were mediated via the type-1 IGF receptor. The increased responsiveness of mature granulosa cells to IGFs may be an important mechanism by which granulosa cells increase their steroidogenic output in the preovulator y follicle.