The cyclic process of ovarian folliculogenesis is an exponential rather than a linear process marked by dramatic proliferation and differentiation of the developing granulosa cell. Although the central role(s) of gonadotropins and of gonadal steroids in this explosive agenda is well accepted, the variable fate of follicles afforded comparable gonadotropic stimulation suggests the existence of additional intraovarian modulatory systems. Amongst potential novel intraovarian regulators, Somatomedin-C/Insulin-like growth factor I (referred to herein as IGF-I) has been the subject of increasingly intense investigation. Considered in aggregate, these studies strongly suggest the existence of an intraovarian autocrine control mechanism, wherein IGF-I may serve as the central signal, and the granulosa cell its site of production, reception, and action. In this capacity, IGF-I may promote the replication and/or cytodifferentiation of the developing granulosa cell, acting largely (but not exclusively) as an amplifier of gonadotropin action. To further evaluate the potential relevance of IGF- I to ovarian physiology, a series of studies are proposed on the developmental control, hormonal regulation, and cellular localization of ovarian IGF-I and its receptor. In this connection, parallel measurements of the corresponding gene transcripts as well as of their presumptive protein products will be carried out. Continued attention will be paid to the cellular mechanism(s) and site(s) of IGF-I action in the granulosa cell, concentrating on the role(s) of G proteins of the adenylate cyclase complex as well as on the involvement of cAMP-dependent protein kinase. Lastly, we propose, for the first time, to study the characteristics, role and regulation of a functional granulosa cell- generated IGF-I binding protein, an exciting development concerned with the amplification of IGF-I and hence gonadotropin action. The long term goal of this investigation is to develop an understanding of the molecular mechanism(s) by which IGF-I may participate in the organization of the follicular apparatus and in the control of its growth and differentiation. Such studies should include an evaluation of the significance of IGF-I to intraovarian paracrine interactions and the provision of irrefutable in vivo evidence for its role in normal ovarian physiology.
Showing the most recent 10 out of 80 publications
