title: Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)₂vitamin D₃: genomic and non-genomic mechanisms.
abstract: The conformationally flexible secosteroid, 1α,25(OH)₂vitamin D₃ (1α,25(OH)₂D₃) 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)₂D₃, 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)₂D₃. 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)₂D₃/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.
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ 85004, USA. haussler@u.arizona.edu
authors.forename: Mark R
authors.initials: MR
authors.lastname: Haussler
authors.forename: Peter W
authors.initials: PW
authors.lastname: Jurutka
authors.forename: Mathew
authors.initials: M
authors.lastname: Mizwicki
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Norman
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D018167:Receptors, Calcitriol; D002117:Calcitriol