Nehring Jamie A, Zierold Claudia, DeLuca Hector F
Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10006-9. doi: 10.1073/pnas.0703512104. Epub 2007 May 29.
The physiological ligand for the vitamin D receptor (VDR) is 1,25-dihydroxyvitamin D(3). Lithocholic acid (LCA), a bile acid implicated in the progression of colon cancer, was recently shown to bind to VDR with low affinity and increase expression of the xenobiotic enzymes of the CYP3A family. Thus, LCA can induce its own catabolism through the VDR. We have now found that LCA can substitute for vitamin D in the elevation of serum calcium in vitamin D-deficient rats. Further, LCA in the diet will also replace vitamin D in the mobilization of calcium from bone. Further, LCA induces CYP24-hydroxylase mRNA gene expression in the kidney of vitamin D-deficient rats. It is clear, therefore, that LCA can be absorbed into the circulation to bind to the VDR at extra-intestinal sites. These findings lend support for the idea that the VDR may have evolved from an original role in detoxification.
维生素D受体(VDR)的生理配体是1,25 - 二羟基维生素D(3)。石胆酸(LCA)是一种与结肠癌进展有关的胆汁酸,最近发现它能以低亲和力与VDR结合,并增加细胞色素P450 3A(CYP3A)家族外源性酶的表达。因此,LCA可通过VDR诱导自身的分解代谢。我们现在发现,LCA可以替代维生素D提高维生素D缺乏大鼠的血清钙水平。此外,饮食中的LCA在促进骨钙动员方面也能替代维生素D。此外,LCA可诱导维生素D缺乏大鼠肾脏中CYP24 - 羟化酶mRNA基因的表达。因此,很明显,LCA可以被吸收进入循环系统,在肠道外部位与VDR结合。这些发现支持了VDR可能从最初的解毒作用进化而来的观点。