Transcriptional regulation of hypothalamic corticotropin-releasing factor gene.

Corticotropin-releasing factor (CRF) plays a central role in regulating stress responses. Forskolin or pituitary adenylate cyclase-activating polypeptide stimulates adenylate cyclase and then increases intracellular cAMP levels in hypothalamic cells. Activation of the protein kinase A pathway leads to binding of cAMP response element (CRE)-binding protein (CREB) on the CRF promoter. Forskolin-stimulated CRF gene transcription is mediated by CRE on the CRF 5'-promoter region. Inducible cAMP-early repressor suppresses a stress response via inhibition of the cAMP-dependent CRF gene. Glucocorticoid-dependent repression of cAMP-stimulated CRF promoter activity is mediated by both nGRE and SRE in hypothalamic cells. Interleukin (IL)-6 produced in the hypothalamus stimulates the CRF gene. Suppressor of cytokine signaling-3, which is induced by a cAMP stimulant and IL-6, is involved in the negative regulation of CRF gene expression in hypothalamic cells. Such complex mechanisms would contribute to stress responses and homeostasis in the hypothalamus. Copyright 2010 Elsevier Inc. All rights reserved.