Molecular Biology of Inhibin Action

Inhibins are dimeric glycoproteins that have primarily been studied for their role in antagonism of activin-mediated release of follicle-stimulating hormone (FSH) from gonadotropes of the anterior pituitary. As a member of the transforming growth factor β (TGFβ) superfamily of ligands and receptors, inhibin shares several processing and structural features with other ligands of the family. An inhibin molecule is composed of an α-subunit and a β-subunit, and two isoforms have been widely investigated, inhibin A (α/βA) and inhibin B (α/βB). Each isoform undergoes processing from a large precursor protein to a mature 32- to 34-kDa form, depending upon the degree of glycosylation. In the absence of inhibin, for example, in ovariectomized animals or postmenopausal women, serum FSH levels rise precipitously. In unilaterally ovariectomized animals the brief loss of inhibin results in a sudden rise in FSH, which induces the remaining ovary to compensate with inhibin subunit expression in a large number of antral follicles. FSH levels are restored and the cycle continues. These studies demonstrate the need for ovarian inhibin to maintain normal gonadotropin levels. Recent studies have provided a mechanism of inhibin action that is consistent with its role in reproduction and may expand inhibin function to tissues outside the reproductive axis. Betaglycan is able to bind inhibin, and in the presence of betaglycan, the affinity of inhibin for activin receptors is increased 30-fold. Through interaction with the coreceptor, inhibin can disrupt activin interaction with its receptors and can also disrupt the interaction of activin receptors with other members of the TGFβ superfamily, such as the bone morphogenetic proteins. These new studies provide evidence for inhibin activity in numerous organs throughout the body and for mediation of systems controlled by molecules other than activin.

KEYWORDS

Inhibin - TGF - pituitary - ovary - betaglycan - activin

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