Mothers against decapentaplegic-related protein 2 expression in avian granulosa cells is up-regulated by transforming growth factor beta during ovarian follicular development

Although mothers against dpp (MAD) and its related proteins (MADR) are believed to be important components of the cell signaling pathway for the transforming growth factor beta (TGF beta) superfamily, the presence and regulation of these signaling molecules in ovarian cells by TGF beta is not known. In the present studies, we have examined the presence of MADR2 and MADR1, two members of the MADR family, in hen granulosa cells at different stages of follicular development. The influence of TGF beta in vitro on their expression was assessed, particularly in the context of TGF beta-induced down-regulation of cytosolic phospholipase A(2) (cPLA(2)), a key enzyme in the biosynthesis of eicosanoids. We have demonstrated for the first time the presence of MADR2 and MADR1 in hen granulosa cells at different stages of Follicular development. The expression of MADR2, but not of MADR1, was up-regulated by TGF beta in vitro in a concentration-and time-dependent manner. Granulosa cell MADR2 expression was maximal during early stages of follicular development, when the granulosa cell cPLA(2) system is most responsive to the growth factor. The changes in MADR2 expression were accompanied by reciprocal alterations in the expression of cPLA(2). These findings are consistent with the hypothesis that homologous up-regulation of MADR2 in granulosa cells may be an important determinant in its follicular stage-specific responsiveness to TGF beta and possibly in the suppression of cPLA(2) gene transcription by the growth factor.