Extinction of prolactin gene expression in somatic cell hybrids is correlated with the repression of the pituitary-specific trans-activator GHF-1/Pit-1.

The tissue-specific expression of the PRL and GH genes is dependent on the presence of a pituitary-specific trans-activator, GHF-1/Pit-1. Previous studies indicate that somatic cell hybridization of rat pituitary GH3 cells with LB82 mouse fibroblasts frequently results in the extinction of GH and PRL expression. The extinction of the GH gene occurs at the transcriptional level, and is accompanied by repression of GHF-1/Pit-1 synthesis. To elucidate the mechanism of PRL extinction we further characterized these same somatic cell hybrid lines as well as the parental GH3 and LB82 cells. The pattern of PRL extinction and reexpression paralleled that of GH in the three hybrid lines that were examined. Two of these lines extinguished both GH and PRL synthesis, while a third displayed reexpression of both genes, apparently due to the loss of mouse chromosomal material. These studies revealed that the extinction of PRL expression in these hybrid lines occurs at the level of mRNA accumulation and is strongly correlated with the loss of GHF-1/Pit-1 mRNA and protein synthesis. These data suggest that in pituitary x fibroblast hybrids repression of the trans-activator GHF-1/Pit-1 is a primary mechanism for the extinction of PRL and GH gene expression.