Using primary cultures of dispersed rat fetal hypothalami, we studied the effect of forskolin and the phorbol ester 12-o-tetradecanoyl phorbol 13-acetate, activators of protein kinase A and C, respectively, on corticotropin-releasing hormone (CRH) regulation. CRH mRNA accumulation and peptide release were stimulated by both agents, indicating that the protein kinase A and protein kinase C messenger systems are involved in the regulation of CRH gene expression and are functional in hypothalamic neurons isolated from fetal brain. © 1990 by The Endocrine Society.