Roles of inhibins, activins, and follistatin in the female reproductive system.

Some 10 years have elapsed since inhibins were first isolated from ovarian follicular fluid and characterized as disulphide-linked dimeric glycoproteins capable of selectively suppressing the synthesis and secretion of follicle-stimulating hormone (FSH) by pituitary gonadotropes. There have been numerous surprises subsequent to this break-through, including the discovery and molecular characterization of activins and follistatins, proteins which share with inhibin an ability to modulate pituitary FSH secretion. It has also emerged that (i) inhibins and activins are members of the diverse but structurally related transforming growth factor beta (TGF beta) peptide family; (ii) follistatin, although structurally unrelated to the TGF beta family, modulates activin bioactivity by acting as a specific high-affinity binding protein; (iii) inhibins, activins, and follistatin function as intragonadal autocrine/paracrine regulators of follicle cell differentiation and steroidogenesis; (iv) inhibins, activins, and follistatin are expressed and subserve local regulatory roles in numerous extragonadal tissues, including brain, adrenal, bone marrow, and placenta but perhaps most notably in anterior pituitary--the classical target tissue for inhibin; (v) the activin-follistatin system may play a key role in early embryogenesis. This article focuses on these developments of the past decade with particular reference to the distribution and functional roles of inhibins, activin, and follistatin in tissues related to the female reproductive system, including hypothalamus, anterior pituitary, ovary, and placenta.