Inhibin and Activin Production in Human Placenta

IN 1985 and 1986, inhibin and activin, respectively, were successfully isolated from follicular fluid of the ovary (1, 2). Since then, our understanding of the important roles of these two new hormones in the reproductive endocrine system has rapidly advanced (3–6). The physiological significance and relationship between inhibin and activin or its related peptides represents one of the most challenging and interesting research areas in reproductive endocrinology. Inhibin is a 32-kDa heterodimer glycoprotein composed of an α-subunit and one of two related β-subunits, termed inhibin A (α-βA) or inhibin B(α-βB). Activin is a 24-kilodalton (kDa) homodimer consisting of two inhibin β-subunits. Three iso forms of activins have been found with different combinations of the subunits, including activin A (βA-βA), activin B(βB-βB), and activin AB (βA-B) (1–4). These structurally related peptides display distinct functions in the regulation of the release of FSH: inhibin selectively suppresses FSH secretion from the pituitary gland, whereas activin stimulates the FSH production (4, 5, 7, 8). Inhibin and activin also manifest many other biological activities. In women, these peptides play roles in the regulation of hormonal production, folliculogenesis and oocyte maturation in the ovary, and embryofetal development (4–6, 9). It has been found that theprimary structures of inhibin β-subunits are homologous, particularly with regard to the distribution of cysteine residues, to a family of growth factors including transforming growth factor-β (TGFβ), Müllerian duct inhibiting substance, and a protein encoded in the decapentaplegic gene complex in Drosophila (5,10). Furthermore, activin A can potentiate the differentiation of cells such as erythroid progenitor cells inbone marrow cultures (11). Therefore, inhibin and activin should not be considered solely as FSH-releasing regulators. This class of molecules may serve as important autocrine and paracrine factors in the modulation of cellular proliferation and differentiation in different tissues (12). In addition, follistatin, a single-chain glycosylated polypeptide with no structural relationship to inhibin or activin, was also isolated from follicular fluid (3,4). It binds to inhibin and activin and helps to regulate FSH release in the pituitary.