Vitamin D receptor as an intestinal bile acid sensor

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

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801 Scopus citations

Abstract

The vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1α,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.

Original languageEnglish (US)
Pages (from-to)1313-1316
Number of pages4
JournalScience
Volume296
Issue number5571
DOIs
StatePublished - May 17 2002

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    Makishima, M., Lu, T. T., Xie, W., Whitfield, G. K., Domoto, H., Evans, R. M., Haussler, M. R., & Mangelsdorf, D. J. (2002). Vitamin D receptor as an intestinal bile acid sensor. Science, 296(5571), 1313-1316. https://doi.org/10.1126/science.1070477