Novel demonstration of a physiologic/pharmacologic role of insulin-like growth factor-1 in ovulation in rats and action on cumulus oophorus.

Gonadotropins are well known to be the most important stimulus for ovarian follicular development. More recently, there is indirect evidence that insulin-like growth factor-1 (IGF-1) is also a very important autocrine/paracrine factor in folliculogenesis. We had access to an analog of IGF-1, LR3IGF-1, which binds very poorly to IGF-1 binding proteins and therefore was shown by previous investigators to have biologic effects. We studied rats that were superovulated with the use of gonadotropins. We showed that the addition of LR3IGF-1 by infusion further increased the ovulation rate (statistically significant) and increased the ovarian weight in two of three strains of rats. We demonstrated that infusion of LR3IGF-1 or injection of equine chorionic gonadotropin or a combination of these two were associated with oocytes with reduced number of cumulus cells (statistically significant). We conducted an experiment to determine whether in vitro culturing with varying dosage of IGF-1 may stimulate cumulus cell replication to improve the quality of oocyte cumulus complex. IGF-1 did not show any change in this respect. Through these physiologic (pharmacologic) studies, we have shown that IGF-1 (analog) can further increase the ovulation rate induced by gonadotropins.