2ND MESSENGER REGULATION OF MESSENGER-RNA FOR CORTICOTROPIN-RELEASING FACTOR

An understanding of how second messengers and their ligands are coupled to CRF gene activation is necessary if we are to understand the regulation of the CRF gene in physiological and pathological states. The protein kinase A, protein kinase C and glucocorticoid second messenger systems mediate most of the regulation of the CRF gene. In in vitro systems, CRF gene expression is stimulated 20-30-fold by activation of either the protein kinase A or the protein kinase C system. Glucocorticoid is able to inhibit stimulation via both pathways, but appears to be more effective in repressing activation mediated by protein kinase C. Glucocorticoid negative regulation requires the presence of glucocorticoid receptor possessing an intact DNA-binding domain, suggesting that this effect involves binding of the receptor to the CRF promoter. These in vitro studies should serve to guide investigators towards the possible mechanisms underlying CRF gene regulation in vivo.