Inhibition of prolactin gene transcription by transforming growth factor-# in GH3 cells

Abstract

Transforming growth factor-# (TGF#) is a member of a large family of growth factors, several of which regulate pituitary function. TGF# has recently been reported to reduce PRL production by GH4 cells. We have examined the effect of TGF# on PRL gene expression in rat pituitary tumor GH3 cells. TGF#I or TGF#2 reduced both basal and Ca2+-stimulated PRL mRNA levels. This inhibition was specific, as the mRNA levels for GH, glucose-regulated protein 78, and histone-3 were unaffected by TGF#. Inhibition of PRL gene expression by TGF# was dose dependent in the range of 0.5-10 ng/ml. TGF# inhibited run-on PRL gene transcription in nuclei from treated cells to the same extent that it reduced PRL mRNA levels, indicating a transcriptional mechanism of action. However, TGF# did not affect Pit-1 mRNA levels or run-on transcription of the Pit-1 gene. Thus, TGF# does not appear to act through modification of Pit-1 gene expression. The PRL promotor contains two regions of homology, with a consensus sequence found in the promotors of other TGF#-inhibited genes. These findings are consistent with other studies that have demonstrated transcriptional repression by TGF#. The potency and specificity of the effects of TGF# on PRL gene expression suggest that it may be a physiological regulator of lactotroph function.