Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase Along the Nephron: New Insights into Renal Vitamin D Metabolism

Renal synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a pivotal step in calcium and phosphate homeostasis. Production of 1,25(OH)2D3 is catalyzed by the mitchondrial cytochrome P450, 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-HYD). As a consequence of the tight regulation of vitamin D metabolism during normal physiology, studies of the expression and regulation of 1alpha-HYD have proved remarkably difficult. However, the recent cloning of the gene for 1alpha-HYD has enabled a more comprehensive analysis of the tissue distribution of 1alpha-HYD, as well as the mechanisms involved in controlling 1,25(OH)2D3 production. In particular, an understanding of site-specific expression and regulation of 1alpha-HYD along the nephron might help to elucidate a more versatile role for 1,25(OH)2D3 in renal physiology.