Inhibin and related proteins: localization, regulation, and effects

Inhibin has originally been defined as a gonadal hormone that exerts a specific negative feedback action on the secretion of FSH from the gonadotropic cells of the pituitary gland. The existence of inhibin was postulated by Mottram and Cramer (15) as early as 1923. However, only after reliable and sensitive bioassay systems had been developed for detection and estimation of inhibin and an ample source of inhibin was found in the form of ovarian follicular fluid, was progress made on the isolation and characterization of the hormone. It is apparent now that inhibin, which itself consists of a dimer of two different subunits, alpha and beta, is a member of a much larger family of (glyco)protein hormones and growth factors that includes Müllerian inhibiting substance, transforming growth factor-beta, activin/erythroid differentiation factor, bone morphogenetic proteins, and an insect and a Xenopus protein. All play important roles in cell differentiation. Gonadal inhibin is produced in the Sertoli cells in the testis and in the granulosa cells in the ovary. The production of inhibin is stimulated by FSH, but controversy exists about other factors that might play a role in the regulation of the production of inhibin. It appears likely that inhibin plays an important role in the feedback regulation of peripheral concentrations of FSH during the period in which Sertoli cells and granulosa cells--the target cells for FSH--divide, i.e., during puberty in male animals and during the development of ovarian follicles in female animals. In this way, inhibin may be an important regulator of the number of developing Sertoli cells and of the length of the seminiferous tubuli in the testis and of the number of developing follicles in the ovary. Apart from its function in the pituitary-gonadal axis, inhibin and activin may be produced and act in a number of other organs such as the placenta, hypothalamus, adrenal, and bone marrow. Investigation of the role of the members of the inhibin family in these systems has only begun, but will certainly be a field of major interest in the near future.