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

Abstract

Almost without exception, the studies to date describing the effects of transforming growth factor beta (TGFβ) upon various ovarian cell types have utilized the subtype TGFβ1. Since TGFβ1 and TGFβ2 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. TGFβ1 plus FSH significantly stimulated LHR binding levels by cultured granulosa cells (GC) from prepubertal diethylstilbestrol-treated rats. TGFβ2 produced the same effect. In porcine GC from 1-3-mm antral follicles, TGFβ1 and TGFβ2 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 TGFβ1 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 TGFβ1 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, TGFβ 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, TGFβ up- or down-regulated LHR and FSHR binding coordinately within species. This suggests that the regulation of LHR by TGFβ in turn involves TGFβ-dependent action upon the expression of FSHR. Since TGFβ elicited opposite directional responses in gonadotropin binding in rat vs. porcine GC, the results also caution against unqualified extrapolation between species with respect to mechanisms by which transforming growth factors modulate gonadotropin receptor expression.