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Transforming Growth Factor-β (TGFβ) Inhibits TGF Expression in Bovine Anterior Pituitary-Derived Cells

Department of Clinical Biochemistry, University of Toronto Toronto, Ontario, Canada
Department of Medicine, Division of Endocrinology, University of Alabama Birmingham, Alabama 35294

Address requests for reprints to: Jeffrey E. Kudlow, Department of Medicine, Division of Endocrinology and Metabolism, University of Alabama, UAB Station, Birmingham, Alabama 35294.

Abstract

Transforming growth factor-β1 (TGFβ1) is a multifunctional regulator of cell growth and differentiation. We report here that TGFβ1 decreased the proliferation of nontransformed bovine anterior pituitary-derived cells grown in culture. We have previously demonstrated that these cells express both TGF and its receptor [the epidermal growth factor (EGF) receptor] and that expression can be stimulated by phorbol ester (TPA) and EGF. TGFβ1 treatment over a 2-day period decreased the proliferation of pituitary cells. This decreased growth rate was accompanied by a decrease in the TGF mRNA level. The effect of TGFβ1 on TGF mRNA downregulation was both dose dependent (maximal effect observed at 1.0 ng/ml TGFβ1) and time dependent (minimum of 2-day treatment with TGFβ1 was required before a decrease in TGF mRNA was observed). Studies on TGF mRNA stability indicated that TGFβ1 did not alter the TGF mRNA half-life. Treatment of the TGFβ1 down-regulated cells with EGF resulted in the stimulation of TGF mRNA levels; thus, the TGFβ1-treated cells remained responsive to EGF. The decreased proliferation in response to TGFβ1 could be only partially reversed by simultaneous treatment of the cells with EGF (10^–9 M) and TGFβ1 (3.0 ng/ml). Qualitatively, the TGFβ1-induced reduction of TGF mRNA content was independent of cell density. TGFβ1 treatment of the anterior pituitary-derived cells also reduced the levels of c-myc and EGF receptor mRNA. These results represent the first demonstration of the down-regulation of TGF synthesis by a polypeptide growth factor and suggest that TGFβ1 may be a physiological regulator of TGF production in vivo.

FOOTNOTES

This work was supported by a grant (to J.E.K.) and a graduate student award (to S.G.M.) from the Medical Research Council of Canada.

Received for publication April 3, 1991. Revision received June 13, 1991. Accepted for publication March 7, 1991.

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