Project/Area Number |
04670374
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
内科学一般
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Research Institution | University of Tokyo |
Principal Investigator |
NAKAO Akihide University of Tokyo, lst Department of Internal Medicine, Assistant Professor, 医学部(病), 助手 (10159056)
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Co-Investigator(Kenkyū-buntansha) |
野入 英世 東京大学, 医学部(病), 助手
KWATA Shoji University of Tokyo, lst Department of Internal Medicine, Assistant Professor, 医学部(病), 助手 (00241993)
TANIGUCHI Shigeo University of Tokyo, lst Department of Internal Medicine, Assistant Professor, 医学部(病), 助手 (50188380)
FUKAGAWA Masafumi University of Tokyo, lst Department of Internal Medicine, Assistant Professor, 医学部(病), 助手 (00211516)
EISE Noiri University of Tokyo, lst Department of Internal Medicine, Assistant Professor
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Project Period (FY) |
1992 – 1993
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Project Status |
Completed (Fiscal Year 1993)
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Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
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Keywords | Uremic hyperparathyroidism / PTH / Vitamine D receptor / Reduced phosphorus diet / VitaminD受容体 / 二次性副甲腺機能亢進症 / 1,25(OH)_2ビタミンD受容体 / 副甲状腺細胞増殖調節機構 |
Research Abstract |
The resistance of parathyroid cells to 1,25-dihydroxyvitamin D3(1,25(OH)2D3) in uremic hyperparathyroidism is thought to be caused, in part, by a 1,25(OH)2D3 receptor (VDR) deficiency in the parathyroids. However, results of biochemical studies addressing VDR numbers in the parathyroids are controversial. Several studies have found VDR content to be decreased in the parathyroids in uremic patients and animals, while others have found no such decrease in the parathyroids of uremic animals. To clarify the role of VDR, we investigated VDR distribution in surgically-excised parathyroids obtained from chronic dialysis patients by immunohistochemistry. We classified the parathyroids as exhibiting nodular or diffuse hyperplasia. Our studies demonstrated a lower density of VDR in the parathyroids showing nodular hyperplasia than in those showing diffuse hyperplasia. Even in the parathyroids showing diffuse hyperplasia, nodule-forming areas were present ; these areas were virtually negative for VDR staining. A significant negative correlation was found between VDR density and the weight of the parathyroids. These findings indicate that the conflicting results of biochemical studies may be caused by the heterogeneous distribution of VDR ; the decreased VDR density in parathyroids may contribute to the progression of secondary hyperparathyroidism and to the proliferation of parathyroid cells that is seen in uremia. Next we tried to clarify the effects of the reduced phosphorus diet on secondary hyperparathyroidism using 5/6 kidney ablation rats. The diet containing phosphorus less than 0.3% decreased serum PTH concentration and the expression of mRNA of PTH in parathyroid glands to the level of control animals without affecting serum Ca and vitamin D3 concentration. Thus, it was shown that phosphorus had a direct effects on parathyroid glands in rats of chronic renal failure.
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