The effects of follistatin, activin and inhibin on steroidogenesis by bovine thecal cells

Abstract

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 β subunit was not detected in thecal mRNA, whereas there were very faint bands of inhibin α 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. Correspondence to: Prof. J.K. Findlay, Prince Henry's Institute of Medical Research, P.O. Box 152, Clayton, 3168 Victoria, Australia. Tel.: +61-3-5504396; Fax: +61-3-5506125.