THE EFFECTS OF FOLLISTATIN, ACTIVIN AND INHIBIN ON STEROIDOGENESIS BY BOVINE THECAL CELLS

The paracrine actions of bovine follistatin (FS), human recombinant activin A and bovine inhibin on progesterone (P), androstenedione (A(4)) and inhibin production, were investigated using LH-stimulated immature bovine thecal cells. The presence of FS (3-100 ng/ml) alone caused a dose-dependent stimulation of P production by thecal cells induced by bovine LH (10 ng/ml). The stimulatory effect of FS on P production at 10 or 30 ng/ml was reversed to control levels with the addition of activin (10 or 30 ng/ml). Treatment with FS did not significantly effect on A(4) production. Activin alone had no consistent effect on A(4) production (measured using two different antibodies), but had a dose-dependent inhibitory effect on P production. Treatments of cells with inhibin had no significant effect on the LH-induced production of either P or A(4). Testosterone production in FS; activin- or inhibin-treated cells was not different from controls. Northern analysis showed that inhibin beta subunit was not detected in thecal mRNA, whereas there were very faint bands of inhibin alpha subunit and FS which were attributed to contamination of granulosa cells (GC). We conclude that FS in vitro has a stimulatory effect on P production by bovine thecal cells, and that activin has the ability to reverse the stimulatory effect of P production. Unlike the rat and human thecal cells, activin and inhibin had no significant effect on LH-induced androgen synthesis by bovine thecal cells. We propose that FS secreted by the GC acts as a paracrine modulator upon thecal cells to directly stimulate the production of P independently of activin. In addition, activin by binding to FS or by direct action on thecal cells can antagonise the increase in P production.