Medical therapy for Cushing's disease using 11β-HSD2 inhibitor
| Project/Area Number |
15590975
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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 |
Endocrinology
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| Research Institution | Kochi University (2004)
Nagoya University (2003) |
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Principal Investigator |
IWASAKI Yasumasa Kochi University, Kochi Medical School Hospital, Assistant Professor, 医学部附属病院, 講師 (30303613)
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| Co-Investigator(Kenkyū-buntansha) |
SUDA Toshihiro Hirosaki University, Internal Medicine, Professor, 医学部, 教授 (30075452)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | ACTH / Proopiomelanocortin / Cushing's disease / pituitary adenoma / glucocorticoid / apoptosis / glucocorticoid / Cushing病 / 11β-hydroxysteroid dehydrogenase / SF1 / corticoroph / ステロイド代謝酵素 |
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| Research Abstract |
Cushing's disease is characterized by persistent adrenocorticotropin secretion under hypercortisolemia. To clarify the molecular mechanism, we examined the effect of 11b-hydroxysteroid dehydrogenase (11β-HSD) inhibition on glucocorticoid suppression of ACTH release using murine corticotroph tumor cells. We found that 11β-HSD2 as well as -HSD1 was expressed in the cells, and that its inhibition by carbenoxolone (CBX) significantly improved the negative feedback effect of glucocorticoid. CBX also enhanced apoptosis induced by cortisol. These effects are most likely attributable to inhibition of 11-HSD2, because only cortisol, a substrate of 11β-HSD2, was present in these experimental conditions. We conclude that ectopic expression of 11β-HSD2 is, at least in part, responsible for the impaired glucocorticoid suppression in corticotroph adenoma. Inhibition of 11β-HSD2 may be applicable to the medical therapy for Cushing's disease.
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Report
(3 results)
Research Products
(7 results)
