Metabolism and sites of action of vitamin D in the kidney

Before it exerts its biological action on its target tissues, the circulating form of vitamin D,25-hydroxyvitamin D (25(OH)D), must be metabolized primarily by the kidney either to 1α,25-dihydroxyvitamin D (1,25(OH)2D) or 24,25-hydroxyvitamin D (24,25(OH)2D) by the enzymes 25(OH)D-1α-hydroxylase (1-hydroxylase) or 25(OH)D-24-hydroxylase (24-hydroxylase), respectively. Activities of these two enzymes are under tight hormonal and ionic control and there is, in general, a reciprocal change in activities of the two enzymes: When the 1-hydroxylase activity is stimulated, the 24-hydroxylase activity is suppressed and vice versa [1–3]. In this article we briefly review recent advances in the unique hormonal regulation of 1-hydroxylase and 24-hydroxylase and present the concept of two distinct 1-hydroxylase systems in the mammalian kidney. It has been appreciated that the kidney is among the target organs for vitamin D as well as an endocrine organ. Therefore, we include recent advances in this area including phosphorus and calcium handling by the kidney, localization of enzymes induced by 1,25(OH)2D3along the nephron, that is, calcium binding protein and 24-hydroxylase, the receptors for 1,25(OH)2D, and the proposed mechanisms of vitamin D action. Readers should refer to recent and, in our opinion, excellent review articles for broader aspects of vitamin D metabolism and action [1–4]