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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.
↵* Present address: Department of Organismal Biosystems, Osaka University, Suita, Osaka 565-0871, Japan.
↵† Present address: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA.
↵‡ To whom correspondence should be addressed. E-mail: davo.mango{at}utsouthwestern.edu
