Vitamin D receptor

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Vitamin D receptor
Properties of human protein
Mass / length primary structure 427 amino acids
Secondary to quaternary structure Homodimer; after vitamin D binding heterodimer VDR + RXRA
Cofactor RXRA
Identifier
Gene name VDR
External IDs

The vitamin D receptor ( VDR ) is a calcitriol -binding transcription factor belonging to the family of type II steroid receptors . The receptor belongs to the superfamily of nuclear receptors NR1I1 ( nuclear receptor subfamily 1, group I, member 1 ).

function

The vitamin D receptor has a high affinity for 1,25 (OH) 2 D 3 (calcitriol) and is necessary so that it can develop its hormonal effect in the target cells. It belongs to the family of steroid receptors; it is thus a ligand- activated transcription factor that activates or inhibits the transcription of certain target genes (depending on the gene ) and thus influences the metabolism . 1.25 (OH) 2 D 3 is the preferred ligand of the VDR, it binds up to 100 times more strongly to 1.25 (OH) 2 D 3 than to 25 (OH) D 3 or to 24.25 (OH) 2 D 3 .

A congenital defect in the vitamin D receptor leads to vitamin D-dependent rickets type 2 . The gene coding for the vitamin D receptor is located in humans on chromosome 12 gene locus q13.11.

The discovery of VDR in tissues that are not the calcium - and phosphate - homeostasis serve, led to the discovery of many other functions of free 1,25 (OH) 2 D 3 in the body. These functions are complexly coregulated for specific cells.

Polymorphisms

There are many allelic variants ( genetic polymorphisms ) of the VDR gene on chromosome 12 in the human population , with great differences between individual ethnic groups . These differences are associated with different bone density , different tendencies towards hyperparathyroidism , resistance to vitamin D therapy, susceptibility to infections and tendencies towards certain autoimmune diseases and cancers . A better understanding of this fact would be important for individually adapted vitamin D therapy and prophylaxis.

regulation

The intracellular concentration of the VDR in a 1,25 (OH) 2 D 3 target cell is upregulated by its ligands, in particular by 1,25 (OH) 2 D 3 itself in almost all cells (homologous regulation). It is also upregulated 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 kidney failure that inhibit its function. This explains part of the vitamin D resistance that is common in patients with chronic kidney disease.

credentials

  1. ↑ Moore, DD et al. (2006): International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor . In: Pharmacol Rev 58 (4): 742-759. PMID 17132852
  2. ↑ a b A.S. Dusso, AJ Brown, E. Slatopolsky: Vitamin D. In: American Journal of Physiology-Renal Physiology . 205; 289: p. F8 – F28, doi: 10.1152 / ajprenal.00336.2004 . PMID 15951480 . (Review).

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