Ligand-Independent Actions of the Vitamin D Receptor: More Questions Than Answers

The review discusses the ligand-independent actions of the Vitamin D receptor (VDR), particularly its role in hair follicle cycling and resistance to skin cancer. The VDR can bind to many sites in the genome without its ligand, 1,25(OH)D. The best example of this is in hair follicle cycling, which does not require 1,25(OH)2D. Mice lacking the ability for VDR to bind 1,25(OH)2D can still restore hair follicle cycling. Skin tumor formation after UVB radiation or chemical carcinogens also appears to be partially independent of 1,25(OH)2D. The document also highlights the role of VDR in alopecia, a condition often seen in patients with VDR mutations. Mice without VDR developed their first coat of hair normally, but had impaired reinitiation of anagen after the first cycle. This suggests that VDR plays a crucial role in hair growth, independent of its ligand. The document also discusses the role of VDR in skin tumor suppression. Studies have shown that VDR null mice develop skin tumors after exposure to UVB radiation or the chemical carcinogen DMBA, while mice lacking Cyp27b1 and thus lacking 1,25(OH)2D production do not. The document concludes that understanding the ligand-independent actions of VDR is crucial for a full understanding of VDR mechanisms of action.