| Project/Area Number |
07671298
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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 |
General surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
FUNAHASHI Hiroomi Nagoya Univ.School of Medicine Lecturer, 医学部, 講師 (50135357)
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| Co-Investigator(Kenkyū-buntansha) |
MOROHASHI Kenichiro Kyushu Univ.School of Medicine Research Associate, 大学院医学系研究科, 助手 (30183114)
IMAI Tsuneo Nagoya Univ.School of Medicine Research Associate, 環境医学研究所, 助手 (80252245)
SEO Hisao Nagoya Univ.Res.Inst.Environ.Med.Professor, 環境医学研究所, 教授 (40135380)
TAKAGI Hiroshi Nagoya Univ.School of Medicine Professor, 医学部, 教授 (70154755)
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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 |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Transcription factors / Adrenal Cortex / ACTH (adrenocorticotropic hormone) / Steroidogenesis / ACTH Receptor / ACTH(andrenocorticotropic hormone) / ACTH |
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| Research Abstract |
1) REGULATION OF THE EXPRESSION OF TRANSCRPTION FACTORS BY ACTH IN RAT
Transcription factors such as Ad4BP,NGFI-B and COUP-TF have been shown to bind with the promoter region of the steroidogenic cytochrome P450c21 gene. We thus investigated whether ACTH increses adrenal steroidogenesis through regulation of the expression of these transcription factors. Rats were treated with pharmacological doses of dexamethasone to completely suppress the endogenous secretion of ACTH.At intervals after ACTH administration, expression of Ad4BP、NGFI-B and COUP-TF was evaluated by Northern blot analysis and electrophoretic mobility shift assay (EMSA).
Administration of ACTH resulted in a transient increase in NGFI-B mRNA with a peak at 60 min post-stimulation. No change was observed in the levels of Ad4BP and COUP-TF mRNA.EMSA revealed that ACTH transiently increases DNA binding activity of Ad4BP,indicating that ACTH activates Ad4BP through post-translational modification such as phosphorylation.Futhermo
… More
re, it is demonstrated that ACTH may regulate steroidogenesis through modulation of these transcription factors.
2) EXPRESSION OF Ad4BP、NGFI-B、COUP-TF IN HUMAN ADRENOCORTICAL ADENOMAS
Expression of Ad4Bp、NGFI-B、COUP-TF was studied in the adrenocortical adenomas obtained from 3 patients with Cushing's syndrome and 1 with aldosterone producing adenoma. Adenoma and adjacent non-tumor tissue were carefully separated and kept frozen at-80ﾟC.Total RNA extrated from each tissue was used for the Northern blot analysis. In patients with Cushing's syndrome, the expression of Ad4BP and COUP-TF mRNA was equally observed in the tumors and in the adjacent normal tissues. However, the expression of NGFI-B mRNA was more in the normal tissues than in the tumors. In the patients with aldosterone producing adenoma, Ad4BP mRNA was not detected in the tumor tissue, while it was present in the normal adjacent tissue. NGFI-B and COUP-TF mRNAs were equally detected in the tumor as well as in the normal tissue.
These findings suggest that altered expression of the transcription factors involved in the regulation of steroidogenic P450 genes may be responsible for the multiplicity of steroidogenesis in adrenocortical tumors.
3) EXPRESSION OF ACTH RECEPTOR (ACTH-R) GENES IN ADRENOCORTICAL ADENOMAS
Seven patients with Cushing's syndrome were studied. In normal tissues, ACTH-R mRNA was almost undetectable while it was invariabley detected in tumor tissues. Since ACTH is required for the expression of ACTH-R mRNA in rats, no expression of the mRNA in normal tissue is due to the inhibition of ACTH secretion in the patients with Cushing's synddrome. Expression of the receptor mRNA in the tumor tissue suggest that it may be involved in the pathogenesis of abnormal synthesis of glucocorticoid in the tumor. Less
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