Role of vitamin D and parathyroid hormone on vitamin D metabolism in the kidney.

维生素 D 和甲状旁腺激素对肾脏维生素 D 代谢的作用。

• 批准号: 06454527
• 负责人: SHINKI Toshimasa
• 金额: $ 4.48万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454527/
• 关键词: vitamin D; parathyroid hormone; vitamin D receptor; 1alpha-hydroxylase; 24-hydroxylase; kidney; mRNA; RT-PCR; カルシウム

It is well established that vitamin D_3 is first metabolized in the liver to 25-hydroxyvitamin D_3 and then in the kidney to 1alpha, 25-dihydroxyvitamin D_3.1alpha, 25-Dihydroxyvitamin D_3 synthesized by 25-hydroxyvitamin D_3-1alpha-hydroxylase is biologically the most active metabolite of the vitamin D, and vitamin D receptors mediate its effects by controlling transcription of vitamin D-responsive genes. 24, 25-Dihydroxyvitamin D_3 synthesized by 25-hydroxyvitamin D_3-24-hydroxylase is thought to be an inactive metabolite. The vitamin D endocrine system is regulated reciprocally by renal 25-hydroxyvitamin D_3-1alpha-and 24-hydroxylases. Previously, we reported that renal proximal convoluted tubules, the major site of 1alpha, 25-dihydroxyvitamin D_3 production, have vitamin D receptors. In the presence of vitamin D receptors, renal proximal convoluted tubules cannot maintain the state of enhanced production of 1alpha, 25-dihydroxyvitamin D_3. To clarify this discrepancy, we proposed a … More working hypothesis for the reciprocal control of renal 25-hydroxyvitamin D_3-1alpha-and 24-hydroxylase activities. In the rat models of enhanced renal production of 1alpha, 25-dihydroxyvitamin D_3, expression of vitamin D receptors and 25-hydroxyvitamin D_3-24-hydroxylase mRNAs was strikingly suppressed in renal proximal convoluted tubules, but not in the cortical collecting ducts. In vitamin D deficient rats with up-regulated renal 25-hydroxyvitamin D_3-1alpha-hydroxylase activity, expression of vitamin D receptor mRNA in renal proximal convoluted tubules was also down-regulated, indicating that the down-regulation of vitamin D receptor mRNA is not the result of the enhanced production of 1alpha, 25-dihydroxyvitamin D_3. In Japanese quail models with up-regulated renal 25-hydroxyvitamin D_3-1alpha-hydroxylase activity by sex steroids, expression of vitamin D receptor mRNA was also down-regulated in the kidney, but not in the duodenum. These results suggest that the down-regulation of vitamin D receptors plays a critical role in the production of 1alpha, 25-dihydroxyvitaminD_3 in renal proximal convoluted tubules. Less

维生素D_3首先在肝脏中代谢为25-羟基维生素D_3，然后在肾脏中代谢为1 α，25-二羟基维生素D_3。由25-羟基维生素D_3- 1 α-羟化酶合成的1 α，25-二羟基维生素D_3是维生素D最具生物活性的代谢产物，维生素D受体通过控制维生素D应答基因的转录来介导其作用。24，25-二羟基维生素D_3是由25-羟基维生素D_3-24-羟化酶合成的一种无活性代谢产物。维生素D内分泌系统受肾脏25-羟维生素D_3- 1 α-和24-羟化酶的双重调节。在此之前，我们曾报道，肾近曲小管是1 α，25-二羟维生素D_3产生的主要场所，它含有维生素D受体。在维生素D受体存在的情况下，肾近曲小管不能维持1 α，25-二羟维生素D_3产生增强的状态。为了澄清这种差异，我们提出了一个 ...更多信息 肾25-羟维生素D_3- 1 α-和24-羟化酶活性相互控制的工作假说。在1 α，25-二羟维生素D_3（1alpha，25-hydroxyvitamin D_3，25-hydroxyvitamin D_3，24-hydroxylase，25-hydroxylase，24-hydroxylase，维生素D缺乏大鼠肾25-羟维生素D_3- 1 α-羟化酶活性升高，肾近曲小管维生素D受体mRNA表达也降低，提示维生素D受体mRNA表达的降低不是1 α，25-羟维生素D_3产生增加的结果。在性类固醇上调肾脏25-羟维生素D_3- 1 α-羟化酶活性的日本鹌鹑模型中，肾脏中维生素D受体mRNA的表达也下调，但在十二指肠中没有。结果提示，维生素D受体的下调在近曲小管1 α，25-二羟维生素D_3的产生中起重要作用。少

项目成果

Suda T.,et al.: "The mechanisms of regulation of vitamin D metabolism in the kidney." Current Opinion in Nephrology and Hypertension. 3. 59-64 (1994)

Suda T. 等人：“肾脏维生素 D 代谢的调节机制”。

Ohyma, Y. et al.: "Identification of a vitamin D-responsive element in the 5'-flanking region of the rat 25-hydroxyvitamin D_3 24-hydroxylase gene." J. Biol. Chem.269. 10545-10550 (1994)

Ohyma, Y. 等人：“鉴定大鼠 25-羟基维生素 D_3 24-羟化酶基因 5 侧翼区域中的维生素 D 响应元件。”

Imae Y.,et al.: "Biological activities of 24-fluoro-1α,25-dihydroxyvitamin D_2 and its 24-epimer." Biochem.Biophys.Acta.1213. 302-308 (1994)

Imae Y. 等人：“24-氟-1α,25-二羟基维生素 D_2 及其 24-差向异构体的生物活性。”Biochem.Biophys.Acta.1213 (1994)。

Nishimura, A.et al.: "Regulation of messenger ribonucleic acid expression of 1alpha, 25-dihydroxyvitamin D_3." J.Cell Biol.127. 1755-1766 (1994)

Nishimura, A. 等人：“1α, 25-二羟基维生素 D_3 信使核糖核酸表达的调节。”

Suda, T.et al.: "The mechanism of regulation of vitamin D metabolism in the kidney." Current Opinion in Nephrology and Hypertension. 3. 59-64 (1994)

Suda, T.et al.：“肾脏维生素 D 代谢的调节机制。”