Activin, Inhibin, and Follistatin in Ovarian Physiology

This chapter describes the roles of activin, inhibin, and follistatin in ovary. Activin and inhibin are members of the transforming growth factor-β (TGF-β) superfamily of ligands, which also includes the bone morphogenic proteins (BMPs), mullerian inhibiting substance (MIS; antimullerian hormone [AMH]), and growth differentiation factor 9 (GDF-9). Members of this family are assembled from large precursor proteins that are processed and assembled into mature dimers containing a common cysteine-knot motif. The activins are dimers of two β-subunits, βA or βB, assembled into three possible activin dimers: activin A (βAβA), activin B (βBβB),or activin AB (βAβB).The inhibins are heterodimers of one activin β-subunit complexed to a unique α-subunit to produce two isoforms of inhibin: inhibin A (αβA) and inhibin B (αβB). Within the normal female reproductive axis, the inhibins act at two main sites: the pituitary gonadotrope and the ovary. The inhibin α-subunit and mature inhibin dimers are exclusively produced by the granulosa cells of the ovary, whereas the β-subunits and activins are produced by and have actions on a large variety of tissues, including the ovary, the pituitary, the placenta, nervous tissue, and mammary tissue.