Endocrine Abstracts

Inhibins and activins were discovered based on their abilities to inhibit and stimulate follicle-stimulating hormone (FSH) secretion from pituitary gonadotrope cells. These ligands are members of the TGFbeta superfamily of secreted ligands. Current dogma suggests that activin B produced by gonadotropes stimulates FSH production in an autocrine/paracrine manner. Inhibins A and B from the gonads suppress FSH by competing for binding to activin receptors. This binding is aided by the co-receptor betaglycan. Recent research from our lab challenges elements of this model. First, inhibins A and B use distinct co-receptors in gonadotropes to suppress FSH. The newly discovered inhibin B co-receptor, TGFBR3L, may be a new drug target to regulate FSH levels. Second, activin B is dispensable for FSH production. Rather, another TGFbeta ligand, myostatin, which is produced in skeletal muscle, is the main driver of FSH synthesis. Myostatin shares properties with activins, including some receptors and soluble binding proteins. This explains, in part, the misattribution of activin action in FSH regulation. We will discuss the clinical significance of these findings.