Involvement of a negative glucocorticoid response element on corticotropin-releasing factor gene promoter in hypothalamic cells
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概要
- 論文の詳細を見る
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.
- 弘前大学の論文
著者
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Suda T
Department Of Endocrinology And Metabolism Hirosaki University Graduate School Of Medicine
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Suda Toshihiro
Department Of Endocrinology And Metabolism Hirosaki University Graduate School Of Medicine
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Kageyama Kazunori
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine
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IWASAKI YASUMASA
Departments of Endocrinology, Metabolism, and Nephrology, and Neurosurgery, Kochi Medical School, Ko
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Iwasaki Yasumasa
Department Of Endocrinology Metabolism And Nephrology Kochi Medical School Kochi University
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Iwasaki Yasumasa
Departments Of Endocrinology Metabolism And Nephrology Kochi Medical School Kochi University
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Iwasaki Yasumasa
Department Of Clinical Laboratory Medicine Nagoya University School Of Medicine
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Suda Toshihiro
The Third Department Of Internal Medicine Hirosaki University School Of Medicine
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NIGAWARA TAKESHI
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine
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SAKIHARA SATORU
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine
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Sakihara Satoru
Department Of Endocrinology And Metabolism Hirosaki University Graduate School Of Medicine
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Hanada Komaki
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine
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Kasckow John
Department of Psychiatry, University of Cincinnati School of Medicine
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Kageyama Kazunori
Department Of Endocrinology And Metabolism Hirosaki University Graduate School Of Medicine
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Hanada Komaki
Department Of Endocrinology And Metabolism Hirosaki University Graduate School Of Medicine
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Nigawara Takeshi
Department Of Endocrinology And Metabolism Hirosaki University Graduate School Of Medicine
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Kasckow John
Department Of Psychiatry University Of Cincinnati School Of Medicine
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Kageyama Kazunori
Dep. Of Endocrinology And Metabolism Hirosaki Univ. Graduate School Of Medicine Hirosaki Jpn
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