1998 Fiscal Year Final Research Report Summary
Genetic analysis of hormane-producing adenoma
| Project/Area Number |
09671036
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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 | Kanazawa University |
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Principal Investigator |
TAKEDA Yoshiyu Faculty of Medcine, Kanazawa University Associate professor, 医学部, 助教授 (90242544)
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| Project Period (FY) |
1997 – 1998
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| Keywords | hormone-producing adenoma / messenger RNA / aldosterone synthase / adrenal gland / differential display |
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| Research Abstract |
The pathophysiological mechanism of hormone-producing adenoma is unknown. Recently, several researhers habe been reported abnormalities of gene for TSH receptor in thyroid hormone-producing adenoma or mutations of gene for 0-protein in growth hormone-producing pituitary adenoma. Aldosterone-producing adenoma (APA) is characterized by hypertension with excessive production of aldosterone, potassium loss, and suppression of the renin-angiotensin system. Patients with APA are frequently complicated with cardiovascular disease compared with ohter hypertensive patients.
I compared activity of aldosterone synthase and expression of CYP11B2 messenger RNA (mRNA) in mononuclear leukocytes (MNL) from patients with IRA to findings in leukocytes from patients with aldosterone-producing adenoma (APA) and normal controls. Levels of CYP11B2 mRNA were determined by competitive PCR.In the same subjects we sought the chimeric CYP1lB1/CYP11B2 that is candidate gene for glucocorticoid-remediable hyperaldos
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teronism. Southern blot analysis and a long PCR method were used to detect the chimeric gene. Direct sequencing of the CYP11B2 also was performed. No chimeric genes or no mutations in the coding region of the CYP11B2 were found in genomic DNA from these patients. However, both aldosterone synthase activity and CYP11B2 mRNA expression were greater in MNL of patients with IHA than those of patients with APA or controls.
I examined the abnormalities of gene for type I angiotensin II receptor (AT1R) or gene for menin, which is the candidate gene for multiple endocrine neoplasia, in aldosteronomas, and found no mutations in both gene gene for AT1R and menin.
In order to clarify the candidate gene in aldosteronoma, I isolated highly expressed gene in aldosteronomas compared with normal adrenal tissue or non-functioning adrenal adenomas using a fluorescent differential display method. Northern blot analysis showed that this gene was strongly expressed in aldosteronoma, but not in normal adrenal tissue. These results suggest that this gene is one of the candidate gene for aldosteronoma. Less
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Research Products
(2 results)
