Epidermal growth factor and phorbol ester regulate prolactin gene expression via distinct pathways.

Previous studies, involving phosphorylation of cytoplasmic proteins and localization of DNA regulatory elements, have suggested that epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) have similar actions on prolactin (PRL) gene expression by pituitary (GH) cells. However, little is presently known about whether the actions of these two factors involve common gene-distal intermediates. In the present study, we have employed two approaches to examine this question. Chronic exposure of GH3 cells to TPA, which strongly down-regulates protein kinase C activity, completely inhibited acute TPA stimulation of transient expression of a transfected PRL promoter construct ((-187)PRL-CAT), but did not inhibit EGF stimulation of either accumulation of endogenous PRL mRNA or of expression of (-187)PRL-CAT. Furthermore, the acute stimulatory effects of EGF and TPA on expression of (-187)PRL-CAT were additive. Each of these observations implies that EGF and TPA have gene-distal actions on PRL gene expression that are at least partially non-overlapping.