Inhibins, activins and follistatins.

Inhibins are proteins consisting of two subunits, 18 K alpha- and 14 K beta-subunits, linked by disulfide bonds. Two forms of inhibins A and B consisting of a common alpha-subunit and a similar but distinguishable beta-subunit specifically suppress the secretion and cell content of FSH in a delayed action. The production of inhibin is regulated mainly by FSH; therefore, a reciprocal relation between FSH and inhibin is established. Each subunit (alpha-, beta A- or beta B-) is encoded by a different mRNA species. Inhibin secreted in response to FSH from the pituitary originates primarily in the granulosa cells of the ovary and the Sertoli cells or testes. Two beta-subunits, beta A beta A, beta A beta B, or beta B beta B form a new molecule, activin, that has opposite endocrine function to inhibin, but in the presence of inhibin, the activity of inhibin overrode that of activin. Follistatin, a single-chain polypeptide with no structurally similarity to inhibin, also specifically inhibits the release of FSH, approximately one third potency of inhibin. This probably is due to the fact that inhibin suppresses both FSH secretion and cell content of FSH whereas follistatin primarily inhibits the release of FSH. In addition to the endocrine function, these gonadal proteins also exert paracrine function on gonadotropin-mediated steroidogenesis. Outside the reproductive system, inhibin and activin also play a role in hemoglobin production, erythroid cell differentiation; all three proteins, together with TGF beta, are involved in immunosuppresion.