Vitamin D Receptor As an Intestinal Bile Acid Sensor

TLDR

The vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1α,25‑dihydroxyvitamin D₃. We demonstrate that VDR is a highly sensitive receptor for the hepatotoxic bile acid lithocholic acid, and its activation induces CYP3A expression that detoxifies LCA, providing a mechanistic basis for vitamin D’s protective role against colon cancer.

Abstract

The vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]. 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.