DOWN-REGULATION OF TGF-BETA-1 GENE-EXPRESSION IN ANTERIOR-PITUITARY-CELLS TREATED WITH FORSKOLIN

Transforming growth factor beta 1 (TGF-beta 1) has recently been shown to inhibit the growth of lactotropes by an autocrine/paracrine mechan ism. Because the growth and function of lactotropic cells in the anter ior pituitary are under control by hormones that modulate intracellula r cAMP levels, the effect of a cAMP elevating agent forskolin on TGF-b eta 1 and TGF-beta 1 gene expressions in primary cultures of anterior pituitary cells was tested, Treatment with a dose of forskolin (5 mu M ), known to induce PRL gene transcription, significantly inhibited TGF -beta 1 levels in culture medium and TGF-beta 1 mRNA levels in cellula r extracts, Nuclear run-off transcription analysis revealed that the f orskolin effect on TGF-beta 1 mRNA expression is due to reduced transc ription initiation rates. These data suggest that the transcription of TGF-beta 1 may be regulated by cAMP dependent mechanisms in anterior pituitary cells. (C) 1997 Academic Press Limited.