SYNERGISTIC INDUCTION OF ALPHA(2)-MACROGLOBULIN SYNTHESIS BY FIBROBLAST GROWTH FACTOR-II AND TRANSFORMING GROWTH-FACTOR BETA(1) IN BOVINE ADRENOCORTICAL-CELLS

We report here that basic fibroblast growth factor (FGF-2), a potent mitogen for adrenocortical cells, stimulates the expression of alpha(2)-macroglobulin by these cells at a transcriptional level and is synergistic with TGF beta(1) for this effect. This is supported by the following observations: (i) Treatment of adrenocortical cells by FGF-2 resulted in a time-dependent and dose-dependent increase of alpha(2)M synthesis. (ii) FGF-2 did not modify alpha(2)M secretion rate; (iii) The induction of alpha(2)M synthesis by FGF-2 was not observed in the presence of the transcription inhibitor DRB; (iv) The amount of alpha(2)M mRNA was increased by 2 to 3 fold under either FGF-2 or TGF beta(1) treatment; (v) Optimal doses of TGF beta and FGF-2 synergistically increased alpha(2)M synthesis. Since alpha(2)M is a growth factor-binding protein, its regulation by FGF-2 may represent an important feedback mechanism controlling the bioactivity of autocrine regulators (FGF-2, TFG beta) of adrenocortical functions.