Growth differentiation factor-9 stimulates rat theca-interstitial cell androgen biosynthesis

Growth differentiation factor-9 (GDF-9) was shown recently to be essential for early follicular development, including the appearance of the theca lay er. Theca cells provide the androgen substrate for aromatization and estrog en production by granulosa cells. Using biologically active recombinant CDF -9 (rGDF-9) and an androgen-producing immortalized theca-interstitial cell (TIC) line or primary TIG, we have examined the action of this paracrine ho rmone on theca cell steroidogenesis. The effect of GDF-9 on TIC progesteron e synthesis was marginal and inconsistent in the primary cultures. In immor talized theca cells, CDF-9 attenuated the forskolin-stimulated progesterone accumulation. More significantly, this oocyte-derived growth factor enhanc ed both basal and stimulated androstenedione accumulation in the primary an d transformed TIC cultures. The effects of GDF-9 on steroidogenesis by preo vulatory follicles were relatively modest. Likewise, it did not affect the maturation of follicle-enclosed oocytes. The effect of GDF-9, an oocyte pro duct, on TIC androgen production suggests a regulatory role of the oocyte o n theca cell function and hence on follicle development and differentiation . This direct effect of CDF-9 on thecal steroidogenesis is consistent with its recently demonstrated actions on thecal cell recruitment and differenti ation.