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. 2002 May 17;296(5571):1313-6.
doi: 10.1126/science.1070477.

Vitamin D receptor as an intestinal bile acid sensor

Makoto Makishima  1 , Timothy T Lu, Wen Xie, G Kerr Whitfield, Hideharu Domoto, Ronald M Evans, Mark R Haussler, David J Mangelsdorf
Affiliations

Vitamin D receptor as an intestinal bile acid sensor

Makoto Makishima et al. Science. .

Abstract

The vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 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.

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