Stay tuned to PXR: an orphan actor that may not be D-structive only to bone
J. Clin. Invest. Michael F. Holick, et al. 115:32 doi:10.1172/JCI23995 [Go to this article.]

Figure 1
A schematic illustrating how xenobiotics and drugs that activate PXR can disrupt vitamin D metabolism and vitamin D function. The kidney is responsible for converting 25(OH)D to 1,25(OH)₂D. Once formed, 1,25(OH)₂D enters the blood and travels to its calcium-regulating target tissues, where it interacts with its specific nuclear VDR. This complex binds RXR, and the resulting heterodimeric complex binds to specific VDREs in the DNA, leading to regulation of gene expression responsible for calcium and bone metabolism. 25(OH)D can also be metabolized in a wide variety of tissues, including colon, prostate, breast, and skin, where it acts either as an autocrine or paracrine hormone to regulate cell growth and carry out other physiologic functions. Xenobiotics and drugs that activate PXR bind RXR. This heterodimeric complex is recognized by the VDRE of CYP24, which is responsible for the destruction of 1,25(OH)₂D into a water-soluble, inactive metabolite. The activated PXR-RXR complex may also be able to alter other VDREs that have wide-ranging biologic functions in cell growth and maturation, immunomodulation, renin and insulin production, and osteoblast function. Understanding of the consequences of this potential interaction and alteration of VDRE gene expression on noncalcemic functions of vitamin D requires further investigation.