Transforming growth factor beta modulates gonadotropin receptor expression in porcine and rat granulosa cells differently

Almost without exception, the studies to date describing the effects of transforming growth factor beta (TGF beta) upon various ovarian cell types have utilized the subtype TGF beta 1. Since TGF beta 1 and TGF beta 2 have been demonstrated to influence major developmental processes differentially during hematopoiesis and embryogenesis, we investigated in two species (rat and pig) whether they might also differentially modulate principal regulatory processes of ovarian cellular differentiation, specifically FSH and/or LH receptor (FSHR, LHR) expression. TGF beta 1 plus FSH significantly stimulated LHR binding levels by cultured granulosa cells (GC) from prepubertal diethylstilbestrol-treated rats. TGF beta 2 produced the same effect. In porcine GC from 1-3-mm antral follicles, TGF beta 1 and TGF beta 2 again acted similarly, but the direction of the response was opposite to that in the rat GC system. This difference could not be ascribed to the fact that the GC utilized represented different stages of follicular development in vivo because TGF beta 1 also potentiated FSH-dependent LHR induction in GC from antral follicles of cycling rats at all stages of the estrous cycle. The major effect of TGF beta 1 on FSHR expression in the rat system was to increase binding by attenuating the down-regulatory action of cholera toxin (CTX) or FSH. In the porcine system, TGF beta reduced FSHR binding at FSH or CTX concentrations that enhanced expression, and it did not attenuate the down-regulatory effect of FSH or CTX at higher doses. In summary, TGF beta up- or down-regulated LHR and FSHR binding coordinately within species.