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Involvement of a negative glucocorticoid response element on corticotropin-releasing factor gene promoter in hypothalamic cells Kageyama, Kazunori Hanada, Komaki Iwasaki, Yasumasa Sakihara, Satoru Nigawara, Takeshi Kasckow, John Suda, Toshihiro 491.4 基礎医学 cyclic AMP corticotropin-releasing factor receptor glucocorticoids hypothalamus promoter application/pdf Corticotropin-releasing factor （CRF） plays a central role in controlling the hypothalamic-pituitary-adrenalaxis during stressful periods. CRF, produced in the hypothalamic paraventricular nucleus （PVN） in response tostress, stimulates adrenocorticotropic hormone （ACTH） release in the anterior pituitary. ACTH then stimulatesglucocorticoid release from the adrenal glands. Glucocorticoid in turn inhibits hypothalamic PVN production of CRFand pituitary production of ACTH. We previously demonstrated that protein kinase A（ PKA） pathway takes a mainpart in producing CRF in the hypothalamus. A functional cAMP-response element（ CRE） on the 5’-promoter region isimportant to increase CRF gene expression. Glucocorticoids inhibit CRF promoter activity in the pituitary cells, whilein the placenta and the bed nucleus of the stria terminalis, glucocorticoids stimulate it. The eff ect of glucocorticoids onCRF gene, therefore, would be tissue specifi c. Although to study the mechanism regulating CRF transcription in thePVN has been the lack of availability of a representative cell line, a rat fetal hypothalamic cell line has been recentlyavailable. We found that forskolin-stimulated CRF gene transcription is mediated by CRE on the CRF 5’-promoterregion in the hypothalamic cells. Both PKA and, in part, p38 mitogen-activated protein kinase pathways contribute tothe forskolin-induced CRF promoter activity. Glucocorticoid-dependent repression of forskolin-stimulated CRF promoteractivity was localized to promoter sequences between －278 and －249 bp. Taken together, these fi ndings indicate thata negative glucocorticoid regulatory element is critical for the repression of CRF gene in the hypothalamic cells. 弘前医学. 59(Suppl.), 2007, p.S62-S66 弘前大学大学院医学研究科・弘前医学会 2007-11-29 eng journal article VoR http://hdl.handle.net/10129/2218 https://hirosaki.repo.nii.ac.jp/records/3624 AN00211444 0439-1721 弘前医学 59 Supplement S62 S66 https://hirosaki.repo.nii.ac.jp/record/3624/files/HirosakiMedJ_59_S62.pdf application/pdf 218.6 kB 2018-03-13