Insulin-Like Growth Factor Binding Proteins and IGFBP Proteases: A Dynamic System Regulating the Ovarian Folliculogenesis

The aim of the present article is to update our understanding of the expression of the insulin-like growth factor binding proteins (IGFBPs), IGFBP proteases and their implication in the different processes of ovarian folliculogenesis in mammals. In the studied species, IGFs and several small-molecular weight IGFBPs (in particular IGFBP-2 and IGFBP-4) are considered, respectively, as stimulators and inhibitors of follicular growth and maturation. IGFs play a key role in sensitizing ovarian granulosa cells to FSH action during terminal follicular growth. Concentrations of IGFBP-2 and IGFBP-4 in follicular fluid strongly decrease during follicular growth, leading to an increase in IGF bioavailability. Inversely, atresia is characterized by an increase of IGFBP-2 and IGFBP-4 levels, leading to a decrease in IGF bioavailability. Changes in intrafollicular IGFBPs content are due to variations in mRNA expression and/or proteolytic degradation by the pregnancy-associated plasma protein-A (PAPP-A), and likely participates in the selection of dominant follicles. The identification of PAPP-A2, as an IGFBP-3 and -5 protease, and stanniocalcins (STCs) as inhibitors of PAPP-A activity extends the IGF system. Studies on their implication in folliculogenesis in mammals are still in the early stages.