Abstract
This chapter reviews the literature that demonstrates that vitamin D receptor (VDR) is a bile acid sensor and plays an essential role in bile acid homeostasis. Under this, it also takes a look at how this new information regarding VDR provides insight into how a high-affinity hormone and its receptor may have evolved by co-opting an extant system with properties already designed to regulate nutrient absorption. The bile acid, lithocholic acid (LCA), is one of the most toxic bile acids. While LCA binds VDR with much lower affinity than 1α,25-dihydroxyvitamin D, studies in vitamin-D-deficient animals demonstrated that LCA could activate VDR in extraintestinal sites such as kidney and bone and was capable of inducing the same effects on calcium metabolism as vitamin D. Within the intestine, VDR induces expression of cytochrome P450 3A (CYP3A), which in turn detoxifies LCA. Thus activation of VDR by LCA or vitamin D results in the induction of a feed-forward catabolic pathway for LCA in the intestine, implicating a paradigm for how the intestine protects itself from the toxic effects of LCA. Thus, the process of bile acid homeostasis involves an essential role played by Vitamin D.
Published Version
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