New Developments in Our Understanding of the Regulation of Calcium Homeostasis by Vitamin D

Abstract Vitamin D is a principal regulator of calcium homeostasis. 1,25-Dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) is the hormonally active form of vitamin D, the biological actions of which are mediated by the vitamin D receptor (VDR), which heterodimerizes with the retinoid X receptor (RXR). Numerous VDR coregulatory proteins have been reported to be involved in VDR-mediated transcription. Genome-wide studies have noted that the actions of 1,25(OH) 2 D 3 , similar to other steroids, are complex and involve the regulation of gene activity at a range of locations many kilobases from the transcription start site. Although the identification of mechanisms mediating VDR transcription of target genes is one focus of current vitamin D research, other new developments of importance are also reviewed in this chapter, including the identification of CYP2R1 as the most important 25-hydroxylase, studies using mouse models that have challenged the three-step model of intestinal calcium absorption, and in vitro and in vivo studies that suggest that the role of vitamin D in bone is direct and indirect.