Insulin-Like Growth Factor-Binding Proteins and Ovarian Folliculogenesis

In the ovary, insulin-like growth factors (IGFs) enhance both proliferation and differentiation of follicular cells by potentiating gonadotropin's actions. The biological effects of IGFs are strikingly modulated by IGF-binding proteins (IGFBPs), whose levels in follicular fluid dramatically change during folliculogenesis. Indeed, in most mammalian species, follicular growth and atresia are characterized by an increase and a great decrease in the IGFBP-3/IGFBPs < 40 kD (IGFBP-2, -4 and -5) ratio in follicular fluid, respectively. These variations result from both changes in expression of these IGFBPs by follicular cells, and in local degradation by specific intrafollicular proteases. Such changes in IGFBP levels lead to great decrease and increase in IGF bioavailability in atretic and growing healthy follicles, respectively. Hence intrafollicular IGFBPs play a key role in the regulation of follicular development by modulating IGFs and therefore gonadotropin's actions.