The precursor peptide of TRH (prepro-TRH) contains five copes of pro-TRH linked by other peptide sequences. In a heterologous TSH expression assay, we found that prepro-TRH- (160-169) stimulated TSH beta gene promoter activity in a time- and dose-dependent manner, moreover, the effect of prepro-TRH-(160-169) was more rapid and of greater magnitude than that of TRH on TSH beta- directed chloramphenicol acetyltransferase synthesis. In the same cells, we found that prepro-TRH-(160-169) stimulated PRL synthesis and secretion, but the effect was similar in magnitude and duration to that of TRH. The effect of prepro-TRH-(160-169) appears to be additive to that of TRH, suggesting that prepro-TRH-(160-169) may act through a mechanism separate from that of TRH. Thus, prepro-TRH-(160-169) has potent endocritic effects at the level of the genome.