Inhibin--a non-steroidal regulator of pituitary follicle stimulating hormone

Inhibin is a gonadal glycoprotein produced by the granulosa and Sertoli cell under the influence of FSH and acts to specifically suppress pituitary FSH secretion. Recently, ovarian inhibin has been purified from several species and its amino acid sequence deduced using cloning techniques. Inhibin consists of two disulphide-linked heterologous subunits of which the smaller may exist in two different forms accounting for two different forms of inhibin in humans and pigs. Heterogeneity of inhibin also exists as a result of proteolytic processing of the molecule during its passage into the circulation. Significant homology exists between the subunits of inhibin and the dimeric peptides TGF-beta and Mullerian inhibitory substance (MIS), suggesting they are all derived from a common ancestral gene. Furthermore, dimers of the smaller subunit of inhibin (FSH-releasing protein (FRP) or activin) have now been found in follicular fluid (FF) and, along with TGF-beta, shown to be potent and specific stimulators of FSH secretion. These proteins may be involved in controlling FSH by another as yet unknown pathway and may prove to be the FSH-releasing factor, analogous to LHRH, which has been postulated to exist for some years. Inhibin can no longer be simply considered as an isolated FSH-suppressing protein. The physiological significance and relationship between inhibin and its related proteins represent one of the most challenging and interesting areas in reproductive endocrinology. Further studies, particularly with the development and use of sensitive assays for both the FSH releasing hormone and inhibin will clarify their role in reproduction and their usefulness in monitoring or treating fertility.