Polypeptide hormone regulation of gene expression. Thyrotropin-releasing hormone rapidly stimulates both transcription of the prolactin gene and the phosphorylation of a specific nuclear protein.

The tripeptide hypothalamic releasing factor, thyrotropin-releasing hormone (TRH), rapidly increases prolactin gene transcription 7- to 12-fold in the GH4 rat pituitary cell line. The maximal rates of transcription are achieved within minutes and begin to attenuate within 1 h following addition of TRH. This transcriptional response appears to account for the observed effects of TRH on the accumulation of prolactin mRNA and the stimulation of prolactin biosynthesis. The rapid transcriptional effects of TRH include a large number of polymerase II-catalyzed transcription units. Addition of TRH to GH4 cell cultures also rapidly induces the phosphorylation of a 23,000-dalton chromatin-associated basic protein, distinct from known high mobility group or histone proteins and referred to as basic regulated phosphoprotein. The time course of TRH-stimulated prolactin transcription and basic regulated phosphoprotein phosphorylation demonstrates that the signal generated by TRH binding to its plasma membrane receptor rapidly reaches the cell nucleus.