Downregulation 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 mechanism. Because the growth and function of lactotropic cells in the anterior pituitary are under control by hormones that modulate intracellular cAMP levels, the effect of a cAMP elevating agent forskolin on TGF-beta 1 and TGF-beta 1 gene expression in primary cultures of anterior pituitary cells was tested. Treatment with a dose of forskolin (5 microM), known to induce PRL gene transcription, significantly inhibited TGF-beta 1 levels in culture medium and TGF-beta 1 mRNA levels in cellular extracts. Nuclear run-off transcription analysis revealed that the forskolin effect on TGF-beta 1 mRNA expression is due to reduced transcription initiation rates. These data suggest that the transcription of TGF-beta 1 may be regulated by cAMP dependent mechanisms in anterior pituitary cells.