Interaction between activin and follicle-stimulating hormone-suppressing protein/follistatin in the regulation of basal inhibin production by cultured rat granulosa cells

There is evidence that FSH-suppressing protein (FSP) antagonizes the action of activin on the differentiation of rat granulosa cells by binding activin in vitro. We tested the interaction of activin and FSP in this in vitro system by examining the effects of FSP on activin dose-related stimulation of immunoreactive inhibin release by rat granulosa cells. Granulosa cells (2 x 10(5) viable cells/well) from diethylstilbestrol-treated immature rats were cultured for 48 h in McCoy's 5a serum-free medium with additives and increasing doses of bovine FSP (0-30 nM) and human recombinant activin (0-20 nM). Inhibin was measured in the medium by RIA. Activin caused a dose-related increase in basal inhibin production, which was maximal between 4-10 nM activin (ED50, 0.6 nM). With the addition of FSP, an apparent increase in the ED50 of the activin dose-response curves was observed, but there were no changes in the maximum response. This pattern closely resembled that of chemical antagonism of an agonist by an agent t...