Corticotropin-releasing hormone gene expression in primary placental cellsis modulated by cyclic adenosine 3 ',5 '-monophosphate

CRH, the principal neuropeptide regulator of pituitary ACTH secretion, is a lso expressed in placenta. Placental CRH has been linked to the process of human parturition. However, the mechanisms regulating transcription of the CRH gene in placenta remain unclear. cAMP signaling pathways play important roles in regulating the expression of a diverse range of endocrine genes i n the placenta. Therefore, we have explored the effect of cAMP on CRH promo ter activity in primary cultures of human placental cells. Both forskolin a nd 8-bromo-cAMP, activators of protein kinase A, can increase CRH promoter activity B-fold in transiently transfected human primary placental cells, i n a manner that parallels the increase in endogenous CRH peptide. Maximal s timulation of CRH promoter activity occurs at 500 mu mol/L 8-bromo-cAMP and 10 mu mol/L forskolin. Electrophoretic mobility shift assay and mutation a nalysis combined with transient transfection demonstrate that in placental cells cAMP stimulates CRH gene expression through a cAMP regulatory element in the proximal CRH promoter region and involves a placental nuclear prote in interacting specifically with the cAMP regulatory element.