Mechanisms and functions of vitamin D

Abstract

The vitamin D hormone, 1,25-dihydroxyvitamin D3, functions by way of a nuclear receptor (vitamin D receptor [VDR]) in a manner analogous to the other members of the steroid-thyroid hormone superfamily. Although the vitamin D receptor has been cloned, its three-dimensional structure remains unknown. The VDR binds to the direct repeat response elements called DR-3 in the promoter region of target genes to stimulate or suppress transcription of those genes encoding for proteins that carry out a wide variety of functions. The binding of the VDR to a DR-3 requires the presence of its ligand and a companion protein, namely the RXR group of retinoid receptors. The RXR binds to the 5' arm of the response element while the VDR binds to the 3' arm. In addition, the transcription factor TFIIB has been shown to bind VDR but there is currently no evidence that a co-repressor or co-activator of VDR is also involved. Phosphorylation of VDR in the transcription complex occurs as does bending of the DNA prior to the initiation or suppression of transcription. As VDR has been detected in cells not previously thought to be target organs, scientists continue to discover new functions of vitamin D. Among these new functions are those noted in the immune system. Experiments in mice have illustrated that the autoimmune diseases of multiple sclerosis and rheumatoid arthritis can be successfully treated with the vitamin D hormone and its analogs. New experiments illustrating the use of the vitamin D hormone and its analogs in suppressing transplant rejection indicate that these compounds may be superior to cyclosporin and may not have the side effects attributed to the cyclosporin immunosuppression therapies.