Epidermal growth factor rapidly stimulates prolactin gene transcription

Abstract

Epidermal growth factor (EGF) was originally characterized as a growth factor for various cell types^1,2 and was subsequently shown to affect a number of cellular and molecular processes^3,4, of which many might be considered as a part of the pleiotropic growth response (enhanced uptake of glucose, uridine and amino acids and stimulated synthesis of protein, RNA and DNA). Very early responses to EGF, such as increased sodium fluxes⁵ and stimulation of tyrosine phosphorylation⁶, have been proposed to mediate some or all of EGF's effects. In a number of tissues, EGF has been shown to increase the synthesis of specific proteins^7–10. We have investigated the effects of EGF on prolactin synthesis in the GH₄ rat pituitary cell line to gain further insight into the mechanism of EGF's actions on cellular functions. Addition of EGF to GH₄ cells results in a three- to sixfold stimulation of prolactin synthesis, as well as a partial inhibition of cell growth^7,8. In this report, we demonstrate that the increased prolactin synthesis appears to be the result of a rapid stimulation of prolactin gene transcription by EGF. It is tempting to speculate that very early transcriptional effects on specific genes, such as reported here in the case of the prolactin gene in GH₄ cells, may mediate some or all of the later effects of EGF on cell cycle regulation in those cells for which it serves as a growth factor.