| Project/Area Number |
07671157
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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 Third Department of Medicine Professor, 医学部, 教授 (30075452)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | CRF / Receptor / ACTH / Vasopressin / Pituitary / Hypothalamus / Cortisol / Cushing's disease / PDMC / レセプター / 遺伝子 / ネルソン症候群 |
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| Research Abstract |
To clarify the pathophysiology of ACTH insufficiency and Cushing's disease, the difference of the regulatory mechanism of CRF type 1 receptor (CRF-R) gene and protein levels between rat anterior pituitary (AP) and human pituitary corticotroph adenoma cells were studied.
AP CRF-R mRNA levels temporarily decreased 1-7 days after bilateral adrenalectomy, and these levels returned to the control level 14 days after surgery. In the rat anterior pituitary cells in vitro, CRF-R mRNA levels were down-regulated 1 hr after incubation with CRF,cAMP,VP and dexamethasone. On the other hand, these levels were up-regulated by CRF and cAMP,but were down-regulated by VP and dexamethasone in corticotroph adenoma cells. Changes in CRF-R protein levels in rat AP in vivo and in vitro were also determined by CRF-R RIA using rat CRF-R C-terminal antiserum and CRF-R C-terminal fragment as a tracer and a standard. CRF-R protein levels also decreased after adrenalectomy and incubation with CRF and cAMP.
These results indicate that the CRF-cAMP system down-regulates CRF-R at mRNA and protein levels and also suggest that the CRF-cAMP system is involved in the mechanism of the development of pituitary microadenoma of Cushing's disease to macroadenoma of Nelson syndrome. Effects of the CRF-cAMP system, VP and dexamethasone on the stability of CRF-R mRNA should be clarified in the near future.
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