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.
Kageyama
Kazunori
K
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
Suda
Toshihiro
T
D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism*; D051786:Cyclic AMP Response Element Modulator / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1
D017362:Cyclic AMP Response Element-Binding Protein; D004967:Estrogens; D011965:Receptors, Glucocorticoid; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D018808:Transcription Factor AP-1; D051786:Cyclic AMP Response Element Modulator; D003346:Corticotropin-Releasing Hormone