Vitamin D receptor as an intestinal bile acid sensor
M Makishima, TT Lu, W Xie, GK Whitfield, H Domoto… - Science, 2002 - science.org
M Makishima, TT Lu, W Xie, GK Whitfield, H Domoto, RM Evans, MR Haussler…
Science, 2002•science.orgThe 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 …
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 …
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.
AAAS