Impaired vitamin D sensitivity.

摘要

Resistance to vitamin D has been known for decades asvitamin D resistant rickets, caused by mutations of the geneencoding for vitamin D receptor (VDR). Findings of extra-skeletaleffects of vitamin D and learning of the molecular mechanismsused by its biologically active metabolite calcitriol revealed otherways leading to its impaired sensitivity. Calcitriol takes advantageof both genomic and non-genomic mechanisms through itsbinding to vitamin D receptor, located not only in the cell nucleibut also in a perinuclear space. On the genomic level thecomplex of calcitriol bound to VDR binds to the DNA responsiveelements of the controlled gene in concert with another nuclearreceptor, retinoid X receptor, and expression of the VDR itself iscontrolled by its own ligand. These elements were found not onlyin the promotor region, but are scattered over the gene DNA.The gene expression includes a number of nuclear transcriptionfactors which interact with the responsive elements and witheach other and learning how they operate would furthercontribute to revealing causes of the impaired vitamin Dsensitivity. Finally, the examples of major disorders are provided,associated with impairment of the vitamin D function and itsreceptor.