Calcitriol receptor
- OMIM: 601769
- UniProt: P11473
Vitamin D receptor (VDR ) is a member of the family of steroid receptors belonging to type II calcitriol -binding transcription factor. The receptor belongs to the superfamily of nuclear receptors NR1I1 ( nuclear receptor subfamily 1, group I, member 2 ).
Function
The vitamin D receptor is a high affinity for 1,25 ( OH) 2D3 ( calcitriol ) and is necessary so that it can exert its hormonal effects in target cells. It belongs to the family of steroid receptors; it is thus a ligand - activated transcription factor that activates or inhibits (depending on the gene) and thus affects the metabolism of the transcription of specific target genes. 1,25 (OH) 2D3, the preferred ligand of the VDR, it binds up to 100 times stronger than to VDR 25 (OH) D3 or 24,25 (OH) 2D3.
A congenital defect in the vitamin D receptor leads to the vitamin D- dependent type 2 Rachtitis The gene encoding the vitamin D receptor gene in humans is on chromosome 12 locus q13.11.
The discovery of the VDR in tissues that do not serve the calcium and phosphate homeostasis, led to the discovery of many other functions of free 1,25 ( OH) 2D3 in the organism. These functions are coregulated cell-specific complex.
Polymorphisms
In the human population there are many allelic variants (genetic polymorphisms ) of the VDR gene on chromosome 12, with large differences between different ethnic groups. These differences are associated with different bone density, different propensity to hyperparathyroidism, resistance to vitamin D therapy, susceptibility to infections and inclination for certain autoimmune diseases and cancers. Better understand this fact would be important for a customized vitamin D therapy and prophylaxis.
Regulation
The intracellular concentration of VDR in a 1,25 ( OH) 2D3 target cell is upregulated by its ligand, in particular by 1,25 ( OH) 2D3 itself in almost all cells (homologous regulation ). He will also up-regulated by other hormones and growth factors that do not bind to VDR. This heterologous regulation has significant species-, tissue-and cell-specific variations.
A modification of the VDR is caused by substances in the primary urine of uremic patients with chronic renal failure, which inhibit its function. This explains some of the vitamin D resistance, which commonly occurs in patients with chronic kidney disease.