Potential Functions of IGFBP-2 for Ovarian Folliculogenesis and Steroidogenesis

Ovarian follicles, as transient structural and functional complexes with the oocyte and the associated cells, determine the female reproductive cycle and thus fertility. Ovarian function is subject to the strict control of hormones and growth factors and thus regulated by auto-, para-, and endocrine mechanisms but influenced also by endogenous factors. During the waves of follicular growth and development, one follicle (monoovulatory) or a limited number of them (polyovulatory) are selected under hypothalamic-gonadal control for maturation until ovulation, resulting in the fertile oocyte. Subordinate follicles inevitably enter different stages of atresia. A number of studies have observed species-specific alterations of IGFBP-2 levels during the phases of growth and development or selection and atresia of follicles. IGFBP-2 is thus probably involved in the process of follicle growth, differentiation, and degeneration. This may occur on the levels of IGF-dependent and -independent growth control but also due to the control of steroidogenesis, e.g., via induction of aromatase expression. In mice, IGFBP-2 delayed reproductive development most probably by IGF-independent mechanisms. Because reproductive development is closely linked to the control of life-or health-span and energy metabolism, we feel that the time is right now to resume research on the effects of IGFBP-2 in the ovarian follicular compartment.