| Project/Area Number |
09671016
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Hirosaki University |
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Principal Investigator |
SUDA Toshihiro Hirosaki University School of Medicine, Department of Medicine, Professor, 医学部, 教授 (30075452)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Cushing's disease / Pituitary adenoma / POMC / protooncogene / gene abnormality / CRF / CRF receptor / プロオピオメラノコルチン / プロトオンコジーン |
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| Research Abstract |
To clarity the mechanism of hypersecretion of ACTH and the resistance of ACTH secretion to glucocorticoid, (1) gene expression of c-fos, (2) gene expression of CRF-R1, (3) response of ACTH to DDAVP and characterization of Vi b mRNA were studied in ACTH-producing pituitary adenoma cells.
(1) c-f os Gene expression of c-fos in corticotroph adenoma cells was greater than that in non-adenoma cells. There were 2 point mutations (somatic mutation) at 5'-UTR in c-fos gene. Fos seems to bind to OR and inhibit OR-induced suppression of POMG gene expression. In addition, Fos may stimulate POMO gene expression.
(2) CRF-R1 mRNA levels were down-regulated by CRF in corticotrophs, but were up-regulated by CRF in corticotroph adenoma cells. These CRF-induced down- and up-regulation of CRF-R1 mRNA levels were mediated by cAMP.VP and glucocorticoid down-regulated CRF-RI mRNA levels in both types of ACTH cells.
(3) DDAVP, V2-agonist, stimulated ACTH secretion from corticotroph adenoma cells, but did not stimulate it in normal ACTH cells. Vib mRNA levels in corticotroph adenoma cells increased after stimulation of VP and CRF.The size of Vib mRNA in adenoma cells was similar to that of authentic V1 b mRNA.
(4) Saikosaponin and serotonin stimulated GRF gene expression in the paraventricular nucleus of the hypothalamus in rats.
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