Synergistic induction of alpha 2-macroglobulin synthesis by fibroblast growth factor-2 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 2M synthesis, (ii) FGF-2 did not modify alpha 2M secretion rate; (iii) The induction of alpha 2M synthesis by FGF-2 was not observed in the presence of the transcription inhibitor DRB; (iv) The amount of alpha 2M 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 2M synthesis. Since alpha 2M 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.
Savona
C
C
INSERM Unité 244, CEA, Biochemie des Régulations Cellulaires Endocrines, DBMS, CEN/G, Grenoble, France.
Keramidas
M
M
Chambaz
E M
EM
Feige
J J
JJ
D000818:Animals; D002417:Cattle; D004357:Drug Synergism; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015383:Zona Fasciculata / Q000187:drug effects*; D000511:alpha-Macroglobulins / Q000096:biosynthesis*
D011994:Recombinant Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000511:alpha-Macroglobulins; D005346:Fibroblast Growth Factors