{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:42:26Z","timestamp":1792392146443,"version":"4.4.0"},"reference-count":26,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5571","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2002,5,17]]},"abstract":"<jats:p>\n                    The vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1\u03b1,25-dihydroxyvitamin D\n                    <jats:sub>3<\/jats:sub>\n                    [1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    ]. 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.\n                  <\/jats:p>","DOI":"10.1126\/science.1070477","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:54:32Z","timestamp":1027749272000},"page":"1313-1316","source":"Crossref","is-referenced-by-count":1085,"title":["Vitamin D Receptor As an Intestinal Bile Acid Sensor"],"prefix":"10.1126","volume":"296","author":[{"given":"Makoto","family":"Makishima","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390\u20139050, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy T.","family":"Lu","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390\u20139050, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Xie","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, Post Office Box 85800, San Diego, CA 92186\u20135800, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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Mice were killed and mRNA from the intestine and liver were isolated for Northern blot analysis (24) using the indicated gene-specific cDNA probes."},{"key":"e_1_3_1_27_2","unstructured":"We thank J. Repa K. Gauthier and N. Kalaany for assistance in animal experiments; C. Wu and A. Kowal for expert technical assistance; C. Haussler and members of the Mango lab for comments; and M. Brown J. Goldstein and D. W. Russell for critically reading the manuscript. D.J.M. and R.M.E. are investigators and M.M. is an associate of the Howard Hughes Medical Institute. T.T.L. is supported by a Pharmacological Sciences training grant from NIH. Funded by the Howard Hughes Medical Institute an NIH Specialized Program of Research Excellence in lung cancer the Robert A. Welch Foundation the Human Frontier Science Program and NIH grants (M.R.H.). Supporting Online Material (www.sciencemag.org\/cgi\/content\/full\/296\/5571\/1313\/DC1) Material and Methods fig. S1"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1070477","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T23:01:19Z","timestamp":1704841279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1070477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,17]]},"references-count":26,"journal-issue":{"issue":"5571","published-print":{"date-parts":[[2002,5,17]]}},"alternative-id":["10.1126\/science.1070477"],"URL":"https:\/\/doi.org\/10.1126\/science.1070477","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,5,17]]}}}