EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA(1) AND ACTIVIN-A ON IN-VITRO PORCINE GRANULOSA-CELL STEROIDOGENESIS

The mammalian ovarian cycle is a strictly regulated process that is de pendent on the intimate interactions among the 3 cell types in the fol licle - theca, granulosa, and oocyte. The cycle has been shown to be c ontrolled by gonadotropins as well as locally produced peptide factors . In this study, an in vitro culture system was used to study the role s of 2 locally produced ovarian peptide factors, transforming growth f actor-beta(1) (TGF-beta(1)) and activin-A, on porcine granulosa cell s teroidogenesis. Gonadotropin-stimulated cultured porcine granulosa cel ls (from medium-sized follicles) were pretreated with 100 ng/ml follic le-stimulating hormone (FSH) for 48 h and then treated with 1 ng/ml TG F-beta(1), 100 ng/ml activin-A, TGF-beta(1) plus activin-A, or receive d no treatment (control) for 48 h. From our previous studies, the conc entrations of the 2 growth factors were determined to produce maximal antisteroidogenic effects in porcine granulosa cells. Progesterone (P- 4) production, estradiol-17 beta (E(2)) production, and aromatase acti vity for gonadotropin-stimulated porcine granulosa cells treated with TGF-beta(1), activin-A, and TGF-beta(1) plus activin-A were significan tly (P < 0.05) reduced from that of the control. The same procedures w ere conducted on basal steroidogenesis studies in which no pretreatmen t with FSH was performed. Both P-4 and E(2) production and aromatase a ctivity for porcine granulosa cells treated with TGF-(beta 1), activin -A and TGF-(beta 1) plus activin-A were significantly (P < 0.05) inhib ited compared with the control. Our results indicate that both TGF-P, and activin-A can inhibit FSH-stimulated and basal steroidogeneses in porcine granulosa cells and, thus, may act as local atretic factors du ring follicular development, When the 2 growth factors were given in c ombination at concentrations that would produce maximal steroidogenic inhibition, they were not able to produce a synergistic effect. These results are consistent with the current theory that TGF-(beta 1) and a ctivin-A may act via the same messenger system, a serine-threonine kin ase.