Epidermal growth factor rapidly stimulates prolactin gene transcription

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Abstract

Epidermal growth factor (EGF) was originally characterized as a growth factor for various cell types1,2 and was subsequently shown to affect a number of cellular and molecular processes3,4, 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 proteins7–10. 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 growth7,8. 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.

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