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

Transforming growth factor-beta (TGF beta) is a member of a large family of growth factors, several of which regulate pituitary function. TGF beta has recently been reported to reduce PRL production by GH4 cells. We have examined the effect of TGF beta on PRL gene expression in rat pituitary tumor GH3 cells. TGF beta 1 or TGF beta 2 reduced both basal and Ca(2+)-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 beta. Inhibition of PRL gene expression by TGF beta was dose dependent in the range of 0.5-10 ng/ml. TGF beta 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 beta did not affect Pit-1 mRNA levels or run-on transcription of the Pit-1 gene. Thus, TGF beta 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 promoters of other TGF beta-inhibited genes. These findings are consistent with other studies that have demonstrated transcriptional repression by TGF beta. The potency and specificity of the effects of TGF beta on PRL gene expression suggest that it may be a physiological regulator of lactotroph function.