Pituitary FSH is released by a heterodimer of the β-subunits from the two forms of inhibin

Abstract

Inhibin is a gonadal protein that specifically inhibits the secretion of pituitary follicle-stimulating hormone (FSH). Two forms of inhibin (A and B) have been purified from porcine follicular fluid¹ and characterized as heterodimers of relative molecular mass (M_r) 32,000 (ref. 2). Each inhibin is comprised of an identical α-subunit of M_r 18,000 and a distinct but related β-subunit of M_r 13,800–14,700 linked by interchain disulphide bond(s). Throughout the purification of inhibins, we consistently observed two fractions which stimulated the secretion of pituitary FSH. We report here the isolation of one of the FSH-releasing proteins; it has a M_r of 24,000 and its N-terminal sequences up to residue 32 are identical to those of each β-subunit of inhibins A and B. In the presence of reducing agents, SDS-polyacrylamide gel electrophoresis resolves the FSH-releasing substance into two subunits which are identical in their migration behaviour to the reduced β-subunits of inhibins A and B. Based on the N-terminal sequence data and M_r of the intact and reduced molecules, we propose that the FSH-releasing substance, which is active in picomolar concentrations, is a heterodimeric protein composed of the two β-subunits of inhibins A and B linked by interchain disulphide bond(s). The structural organization of the FSH-releasing substance is homologous to that of transforming growth factor-β (TGF-β)³, which also possesses FSH-releasing activity in the same bioassay⁴. We suggest that the substance be called activin to signify the fact that it has opposite biological effects to inhibin.