Inhibition of Prolactin Gene Transcription by Transforming Growth Factor-β in GH₃Cells

Transforming growth factor-β (TGFβ) is a member of a large family of growth factors, several of which regulate pituitary function. TGFβ has recently been reported to reduce PRL production by GH4 cells. We have examined the effect of TGFβ on PRL gene expression in rat pituitary tumor GH3 cells. TGFβ1 or TGFβ2 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 TGFβ. Inhibition of PRL gene expression by TGFβ was dose dependent in the range of 0.5–10 ng/ml. TGFβ inhibited runon 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, TGFβ did not affect Pit-1 mRNA levels or run-on transcription of the Pit-1 gene. Thus, TGFβ 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 TGFβ-inhibited genes. These findings are consistent with other studies that have demonstrated transcriptional repression by TGFβ. The potency and specificity of the effects of TGFβ on PRL gene expression suggest that it may be a physiological regulator of lactotroph function.