Glucocorticoids and the TGF-β family of cytokines can act as opposing regulators of certain physiological processes. A potential mechanism underlying this antagonistic relationship is now reported by Song et al. The glucocorticoid receptor (GR) appears to directly interact with and inhibit Smad3, an intracellular signaling component of the TGF-β pathway. The Smad3-Smad4 complex translocates into the nucleus where it binds to a recognition sequence in the promoter region of gene targets. Cells that overexpressed the GR responded to exogenous glucocorticoid by inhibiting Smad3 and repressing TGF-β induced expression of a reporter construct. Glucocorticoid repression of TGF-β was not reciprocal in that the cytokine did not inhibit glucocorticoid signaling. The study suggests an important role for the GR in mediating the biological effects of TGF-β.
Song, C-Z., Tian, X., and Gelehrter, T.D. (1999) Glucocorticoid receptor inhibits transforming growth factor-β signaling by directly targeting the transcriptional activation function of Smad3. Proc. Natl. Acad. Sci. U.S.A. 96: 1176-11781. [Abstract] [Full Text]