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Endocrinology Vol. 138, No. 9 3659-3665
Copyright © 1997 by The Endocrine Society

ARTICLES

Mothers Against Decapentaplegic-Related Protein 2 Expression in Avian Granulosa Cells Is Up-Regulated by Transforming Growth Factor ß during Ovarian Follicular Development1

Ming Li, Julang Li2, Pamela A. Hoodless, Tomoo Tzukazaki, Jeffrey L. Wrana, Liliana Attisano and Benjamin K. Tsang

Reproductive Biology Unit (M.L., J.L., B.K.T.), Department of Obstetrics and Gynaecology and Department of Physiology, University of Ottawa, Ottawa Civic Hospital Loeb Research Institute, Ottawa, Ontario, Canada K1Y 4E9; Program in Developmental Biology and Division of Gastroenterology (P.A.H., T.T., J.L.W.), Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8; and Department of Anatomy and Cell Biology (L.A.), University of Toronto, Toronto, Ontario, Canada M5S 1A8

Address all correspondence and requests for reprints to: Dr. Benjamin K. Tsang, Department of Obstetrics and Gynaecology, Ottawa Civic Hospital, 1053 Carling Avenue, Ottawa, Ontario, Canada K1Y 4E9. E-mail: ben{at}civich.ottawa.on.ca

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 ß (TGFß) superfamily, the presence and regulation of these signaling molecules in ovarian cells by TGFß 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 TGFß in vitro on their expression was assessed, particularly in the context of TGFß-induced down-regulation of cytosolic phospholipase A2 (cPLA2), 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 TGFß 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 cPLA2 system is most responsive to the growth factor. The changes in MADR2 expression were accompanied by reciprocal alterations in the expression of cPLA2. 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 TGFß and possibly in the suppression of cPLA2 gene transcription by the growth factor.




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