Vitamin D receptor as an intestinal bile acid sensor
Vitamin D receptor as an intestinal bile acid sensor
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DOI：
10.1126/science.1070477
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发表时间：
2002-05-17
期刊：
影响因子：
56.9
通讯作者：
Mangelsdorf, DJ
中科院分区：
文献类型：
--
作者：
Makishima, M;Lu, TT;Mangelsdorf, DJ
The vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1alpha-,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. We show that VDR also functions as a receptor for the secondary bile acid lithocholic acid (LCA), which is hepatotoxic and a potential enteric carcinogen. VDR is an order of magnitude more sensitive to LCA and its metabolites than are other nuclear receptors. Activation of VDR by LCA or vitamin D induced expression in vivo of CYP3A, a cytochrome P450 enzyme that detoxifies LCA in the liver and intestine. These studies offer a mechanism that may explain the proposed protective effects of vitamin D and its receptor against colon cancer.
