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

Research output: Contribution to journalArticle

768 Citations (Scopus)

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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Calcitriol Receptors
Lithocholic Acid
Bile Acids and Salts
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP3A
Calcitriol
Cytoplasmic and Nuclear Receptors
Vitamin D
Carcinogens
Colonic Neoplasms
Intestines
Hormones
Liver

ASJC Scopus subject areas

  • General

Cite this

Makishima, M., Lu, T. T., Xie, W., Whitfield, G. K., Domoto, H., Evans, R. M., ... 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

Vitamin D receptor as an intestinal bile acid sensor. / Makishima, Makoto; Lu, Timothy T.; Xie, Wen; Whitfield, G. Kerr; Domoto, Hideharu; Evans, Ronald M.; Haussler, Mark R.; Mangelsdorf, David J.

In: Science, Vol. 296, No. 5571, 17.05.2002, p. 1313-1316.

Research output: Contribution to journalArticle

Makishima, M, Lu, TT, Xie, W, Whitfield, GK, Domoto, H, Evans, RM, Haussler, MR & Mangelsdorf, DJ 2002, 'Vitamin D receptor as an intestinal bile acid sensor', Science, vol. 296, no. 5571, pp. 1313-1316. https://doi.org/10.1126/science.1070477
Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H, Evans RM et al. Vitamin D receptor as an intestinal bile acid sensor. Science. 2002 May 17;296(5571):1313-1316. https://doi.org/10.1126/science.1070477
Makishima, Makoto ; Lu, Timothy T. ; Xie, Wen ; Whitfield, G. Kerr ; Domoto, Hideharu ; Evans, Ronald M. ; Haussler, Mark R. ; Mangelsdorf, David J. / Vitamin D receptor as an intestinal bile acid sensor. In: Science. 2002 ; Vol. 296, No. 5571. pp. 1313-1316.
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