Disease relevance of VDR

• The aim of the study was the development of vitamin D receptor agonists with decreased metabolic stability for the topical treatment of psoriasis and related hyperproliferative skin diseases [1].
• Their affinity for the vitamin D receptor (from pig intestine) and human vitamin binding protein were reduced, and their potency to induce cell differentiation of human leukemia cells (HL 60) or osteosarcoma cells (MG 63) was markedly reduced (19% and 3%, respectively), in comparison with calcitriol [2].

High impact information on VDR

• Furthermore, this compound interacted as efficiently as 1,25(OH)2D3 with the vitamin D receptor (VDR), retinoid X receptor (RXR), coactivators, and DNA, which illustrated its potent ability to activate the genomic signal transduction pathway [3].
• The 2-ethylidene-19-nor compounds with a methyl group from the ethylidene moiety in a trans relationship to the C(6)-C(7) bond (E-isomers) were more potent than the corresponding Z-isomers and the natural hormone in binding to the vitamin D receptor [4].
• In the studies described here, we compared the expression of calbindin D-28K and the vitamin D receptor (VDR) in four renal cell lines: Madin-Darby bovine kidney (MDBK) cells, Madin-Darby canine kidney (MDCK) cells, LLC-PK1 pig kidney cells and opossum kidney (OK) cells [5].
• Transfection of the h24(OH)ase promoter construct [-5,500/-22 luciferase; vitamin D response elements at -294/-274 and -174/-151; AP-1 site at -1,167/-1,160] in vitamin D receptor (VDR)-transfected COS-7 cells resulted in strong activation by 1,25(OH)(2)D(3) [6].
• The promoter activity was markedly suppressed by 1alpha,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 in presence of vitamin D receptor (VDR) [7].

Biological context of VDR

• Compared to 1 alpha,25(0H)2D3, all analogs had lower affinities for the pig duodenal vitamin D receptor and also for the human serum vitamin D binding protein [8].
• Vitamin D (D) deficiency during human pregnancy appears to disturb fetal growth and mineralization, but fetal development is normal in D-deficient rats and vitamin D receptor gene-ablated mice [9].
• In the intracellular process of the action of calcitriol, vitamin D receptor is thought to undergo some kind of physiochemical change, called activation, before the receptor binds to the vitamin D response element of the gene [10].

Anatomical context of VDR

• The involvement of polyamines in the activation of vitamin D receptor from porcine intestinal mucosa [10].
• All the synthesized vitamins possessing a 25-hydroxylated saturated side chain were slightly less active (3-5X) than 1 alpha,25-dihydroxyvitamin D(3) in binding to the porcine intestinal vitamin D receptor and significantly more potent (12-150X) in causing differentiation of HL-60 cells [11].
• Among the synthesized 19-norvitamin D3 analogs, 2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxy-19-norvitamin D3 (8a) showed almost the same potency in binding to the bovine thymus vitamin D receptor (VDR) as the natural hormone (1), while its beta-isomer had only a 3% affinity [12].

Associations of VDR with chemical compounds

• In sucrose density gradient analysis, polyamines decreased the sedimentation coefficient of vitamin D receptor in a dose-dependent fashion [10].
• The data suggest that VDR-mediated inhibition of 25-hydroxylase(s) by vitamin D3 metabolites at the transcriptional level may play an important role in the regulation of 25-hydroxyvitamin D3 production in liver and other tissues [7].
• Among naturally existing polyamines, spermidine and spermine, but not putrescine, were effective within their physiological intracellular concentrations, suggesting that both spermidine and spermine can activate vitamin D receptor in vivo as well [10].

References