Recent discoveries in physiology of insulin-like growth factor-1 and its interaction with gonadotropins in folliculogenesis.

Ovarian follicular development is under the influence of gonadotrophins. The manner by which gonadotrophins achieve their role in cell replication and hormone production is through other specialized molecules. Insulin-like growth factor-1 (IGF-1) is considered to be one of the most important of these molecules. IGF-1 is present in relatively large amounts in the ovary and the IGF-1 gene is expressed in the graafian follicle. IGF-1 binding proteins modulate the action of IGF-1 and are influenced by gonadotrophins. Null mutations of genes encoding IGF-1 and type-1 IGF receptor have demonstrated the obligatory role of IGF-1 in folliculogenesis. It was proposed that IGF-1 may be an obligatory mediator of gonadotrophin-induced folliculogenesis and that the interaction is synergistic. From this point, one group embarked on a series of physiological studies to further elucidate the interaction of these molecules. We discovered that, according to circumstances, follicle stimulating hormone (FSH) may act with IGF-1 synergistically (as was postulated before), additively, independently, or even antagonistically. We discovered that granulosa cells must first be exposed to FSH and then they respond well to IGF-1. All previous studies of granulosa cells were done on mural granulosa cells. We subsequently showed that cumulus type of granulosa cells (adjacent to the oocyte) behave differently in their responses to gonadotrophins and IGF-1.