4 Activins and Inhibins

Activins and the structurally and functionally related inhibins belong to the transforming growth factor-β (TGF-β) family of growth factors. Activins and inhibins have central roles in regulating follicle-stimulating hormone (FSH) release and in coordinating reproductive physiology. Inhibins function as classical endocrine hormones, whereas both activins and inhibins have localized autocrine and paracrine roles. Activins have additional functions outside of the reproductive systems as regulators of cell growth and differentiation, particularly in response to injury and inflammation. This chapter discusses the mechanisms involved in activin and inhibin activities and the roles of these factors in reproductive and other tissues. STRUCTURES AND SYNTHESIS OF ACTIVINS AND INHIBINS A hormone termed “inhibin” was proposed to exist in 1932 (McCullagh 1932). Inhibin was defined as a nonsteroidal, water-soluble factor in gonadal extracts that prevents stereotypical changes in the morphology of the pituitary that appeared after castration. After the identification of the pituitary cell types and their corresponding hormones, this definition was refined: Inhibin exerts a direct effect on pituitary gonadotrope cells, leading to a specific suppression of FSH release, without altering the release of luteinizing hormone (LH) (de Kretser et al. 1988; Vale et al. 1988). Biochemical purification of inhibin was undertaken using this activity on pituitary cells as an assay. Secretions of various gonadal fluids were found to be rich sources of inhibin and were thus used as source material for purification. Inhibins—and in the process, activins—were eventually purified to apparent homogeneity from these sources based on their effects on FSH...