Vitamin D receptor (VDR)-mediated actions of 1α,25(OH) 2 vitamin D 3: Genomic and non-genomic mechanisms

Mark R. Haussler, Peter W. Jurutka, Mathew Mizwicki, Anthony W. Norman

Research output: Contribution to journalReview articlepeer-review

368 Scopus citations

Abstract

The conformationally flexible secosteroid, 1α,25(OH) 2 vitamin D 3 (1α,25(OH) 2 D 3 ) initiates biological responses via binding to the vitamin D receptor (VDR). The VDR contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that respectively bind a bowl-like ligand configuration (gene transcription) or a planar-like ligand shape (rapid responses). When occupied by 1α,25(OH) 2 D 3 , the VDR-GP interacts with the retinoid X receptor to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1α,25(OH) 2 D 3 . By recruiting complexes of either coactivators or corepressors, activated VDR modulates the transcription of genes encoding proteins that promulgate the traditional genomic functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. 1α,25(OH) 2 D 3 /VDR control of gene expression and rapid responses also delays chronic diseases of aging such as osteoporosis, cancer, type-1 and -2 diabetes, arteriosclerosis, vascular disease, and infection.

Original languageEnglish (US)
Pages (from-to)543-559
Number of pages17
JournalBest Practice and Research: Clinical Endocrinology and Metabolism
Volume25
Issue number4
DOIs
StatePublished - Aug 2011

Keywords

  • coactivator
  • corepressor
  • genomic responses
  • ligand conformation
  • rapid responses
  • retinoid X receptor
  • transcription
  • vitamin D receptor
  • vitamin D responsive elements

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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