Vitamin D is bioactivated in kidney to its hormonal form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), functioning to prevent rickets/osteomalacia by stimulating small intestinal calcium absorption. Plasma 1,25(OH)2D3 is depressed in patients with chronic renal failure and elevated in subjects with calcium urolithiasis, but normal in osteoporosis. The chromosomal gene encoding the nuclear vitamin D receptor (VDR) contains two common polymorphisms that influence VDR functional activity, which encompasses 1,25 (OH)2D3-ligand-dependent heterodimerization with retinoid X receptor (RXR) and recruitment of cell-specific coactivators for enhancement of target gene transcription. A newly discovered ligand for VDR is lithocholic acid (LCA), a secondary bile acid that is a causative agent in colon cancer promoted by high fat diets. LCA activates the VDR-RXR complex in colon to stimulate the transcription of cytochrome P450 3A4, which detoxifies LCA. This process is potentiated by 1,25(OH)2D3 binding to VDR, explaining mechanistically the epidemiologic finding that vitamin D prevents colon cancer.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Clinical Ligand Assay|
|State||Published - Jun 1 2002|
ASJC Scopus subject areas
- Clinical Biochemistry
- Biochemistry, medical