Vitamin D response elements VDREs

As with vitamin A, mast of the effects of vitamin D involve a nuclear receptor. The vitamin D receptor is a member of the steroid/thyroid hormone superfamily of receptors. When I a,2S-OHD binds to its receptor, the complex forms a hetcrodimer with an unoccupied RXR. This heterodimer subsequently binds to the regulatory regions on specific genes in target tissue. These regions are called vitamin D response elements (VDREs). The binding to VDREs can increase or decrease expression of genes. The proteins thus made carry out the functions of vitamin D. 

The active form of vitamin D, 1,25 dihydroxy-vitamin D (l,25(OH)2D), binds to the vitamin D receptor (VDR), which is expressed in most cells. l,25(OH)2D functions as a steroid hormone, usually by heterodimerization with the retinoid X receptor, binding to vitamin-D response elements (VDRE) located in promoter regions. It induces the expression of target genes involved in many cellular responses, including the immune responses. 

Figure 6 A schematic representation of the mechanism of action of 1,25 OH)2D in various target cells resulting in a variety of biological responses. The free form of 1,25(OH)2D3 enters the target cell and interacts with its nuclear vitamin D receptor (VDR), which is phosphorylated (Pi). The 1,25(OH)2D-VDR complex combines with the retinoic acid X receptor (RXR) to form a heterodimer, which, in turn, interacts with the vitamin D responsive element (VDRE), causing an enhancement or inhibition of transcription of vitamin D-responsive genes including calcium-binding protein (CaBP), ECaC, 24-OHase, RANKL, alkaline phosphatase (alk Pase), prostate-specific antigen (PSA), and PTH.

Figure 30-4. Hormone action of 1,25-dihydroxyvitamin D. VDR, vitamin D receptor RXR, retinoic acid receptor VDRE, vitamin D response element.

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