Potential local regulatory functions of inhibins, activins and follistatinin the ovary

The changing pattern of granulosa cell expression of inhibin/activin subuni ts and follistatin during follicle development and their differential regul ation by extrinsic and intraovarian factors supports evidence from function al studies, mostly in vitro, that these proteins have important roles in fo lliculogenesis, oocyte maturation and corpus luteum function. Gonadal inhib ins function as negative feedback hormones to regulate the synthesis and se cretion of pituitary FSH, a key determinant of follicle development, but th ere is little supportive evidence for a peripheral endocrine role for ovary -derived activins or follistatin in this regard. However, activins and foll istatin are expressed in numerous other tissues, including anterior pituita ry, and they are firmly implicated as local intrapituitary regulators of FS H secretion. Intraovarian actions of granulosa cell-derived activins includ e the promotion of granulosa cell proliferation and upregulation of FSH rec eptors, P450arom, oestrogen synthesis, granulosa cell LH receptors and enha ncement of oocyte maturation. Through its activin-binding role, follistatin can reverse each of these activin-induced responses. In addition to their endocrine feedback role, granulosa-derived inhibins can sensitize theca cel ls to LH, thereby enhancing the production of androgens, an essential requi rement for follicular oestrogen synthesis. Activins can oppose this effect and suppress thecal androgen production. Granulosa cells overproduce inhibi n a subunit precursor relative to betaA/betaB subunit precursors and eviden ce indicates that different parts of the inhibin a subunit precursor have i ntrinsic biological activities distinct from inhibin alpha betaA/B dimer, a nd serve as additional local modulators of follicle and corpus luteum funct ion.