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Renal Division, Washington University School of Medicine, St. Louis, Missouri 63110
The vitamin D endocrine systems plays a critical role in calcium and phosphate homeostasis. The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], binds with high affinity to a specific cellular receptor that acts as a ligand-activated transcription factor. The activated vitamin D receptor (VDR) dimerizes with another nuclear receptor, the retinoid X receptor (RXR), and the heterodimer binds to specific DNA motifs (vitamin D response elements, VDREs) in the promoter region of target genes. This heterodimer recruits nuclear coactivators and components of the transcriptional preinitiation complex to alter the rate of gene transcription. 1,25(OH)2D3 also binds to a cell-surface receptor that mediates the activation of second messenger pathways, some of which may modulate the activity of the VDR. Recent studies with VDR-ablated mice confirm that the most critical role of 1,25(OH)2D3 is the activation of genes that control intestinal calcium transport. However, 1,25(OH)2D3 can control the expression of many genes involved in a plethora of biological actions. Many of these nonclassic responses have suggested a number of therapeutic applications for 1,25(OH)2D3 and its analogs.
gene expression; receptor; metabolism
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