Vitamin D:: metabolism, regulation and associated diseases

Vitamin D is well known as a hormone involved in mineral metabolism and bone growth. Conversion into the active metabolite 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) from the precursor is effected by cytochrome P450 enzymes in the liver (CYP27A1 and CYP2R1) and the kidney (CYP27B1). CYP27A1 has been shown to be transcriptionally regulated by nuclear receptors (PPAR alpha, gamma, HNF-4 alpha and SHP) which are ligand-dependent transcription factors. CYP27B1 is tightly regulated by the plasma levels of calcium, phosphate, parathyroid hormone (PTH) and 1,25(OH)(2)D-3 itself. In vitamin D target organs, inactivation of vitamin D is attributed to CyP24A1 which is transcriptionally induced by 1,25(OH)(2)D-3 whose action is mediated by binding to its cognate nuclear receptor, the vitamin D receptor (VDR). Diseases associated to Vitamin D deficiency (rickets in children, and osteomalacia or osteoporosis in adults) and autosomal recessive forms of inherited rickets illustrate the key role of vitamin D in calcium homeostasis and bone metabolism. Recently, discovery of 1,25(OH)(2)D-3 new biological actions that include antiproliferative, prodifferentiating effect on many cell types and immunoregulatory properties creates a growing interest for this vitamin. In this way, a best understanding of various actors implicated in vitamin D metabolism and its regulation is of a major importance to optimise the use of vitamin D in disease prevention.