VITAMIN D (CALCITRIOL)
Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells, and that this hormone has biologic effects which extend far beyond control of mineral metabolism. Vitamin D is thus not a true vitamin, as it can be synthesized in adequate amounts by most mammals exposed to sunlight (cats and dogs cannot synthesize vitamin D and must receive it in their diet). An organic chemical compound (or related set of compounds) is only scientifically called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from their diet. However, as with other compounds commonly called vitamins, vitamin D was discovered in an effort to find the dietry substance that was lacking in a disease, namely, rickets, the childhood form of osteomalacia.
ROLE OF VITAMIN D IN REGULATION OF SEVERAL GENES:
The vitamin D hormones have essential roles in human health. Vitamin D hormones act by binding to and activating the vitamin D receptor (VDR) to regulate the expression of genes in a tissue-specific manner. Vitamin D hormones regulate blood calcium levels by controlling intestinal absorption of dietary calcium and reabsorption of calcium by the kidneys. Concomitantly, vitamin D hormones also suppress the production of the calcium regulating hormone, parathyroid hormone (PTH), which is produced by the parathyroid glands. The vitamin D hormones also participate in the regulation of cellular differentiation and growth, as well as bone formation and metabolism. Additionally, vitamin D hormones are required for the normal functioning of the musculoskeletal, immune and renin-angiotensin systems. There is a growing body of evidence linking vitamin D insufficiency with cognitive and neural dysfunction. The widespread beneficial effects of vitamin D hormones are continually being elucidated through studies directed to the intracellular VDR and the corresponding networks of VDR-responsive genes in nearly every human tissue. It is becoming evident that vitamin D insufficiency has a widespread and significant impact on a number of key physiological systems."
METABOLISM OF VITAMIN D:
Both forms of vitamin D undergo identical metabolism . Some evidence indicates that vitamin D2 may be metabolized more rapidly than vitamin D3, but with regular daily intake they can be considered bioequivalent. Both forms of vitamin D are converted to 25-hydroxyvitamin [25(OH)D] in the liver, and the serum level of 25(OH) D is measured to determine the adequacy of vitamin D status. In the kidney, 25(OH)D is hydroxylated to 1, 25-dihydroxyvitamin D [1, 25(OH)2 D], which is the only biologically active form of vitamin D. Acting principally on the duodenum, 1, 25(OH)2 D increases calcium absorption. It also acts on bone cells, both osteoblasts and osteoclasts, to mobilize calcium. The synthesis of 1, 25(OH)2 D is tightly regulated and stimulated primarily by serum parathyroid hormone
THE VITAMIN D RECEPTER AND MECHANISM OF ACTION:
The vitamin D system is unique in that distinct calcium homeostatic functions and cell growth regulatory activities are mediated through a single ligand, calcitriol, acting through a specific receptor exhibiting ubiquitous tissue expression, the vitamin D receptor (VDR). The VDR is a member of a superfamily of nuclear steroid hormone receptors which regulate gene transcription by interacting with response elements in gene promoters. Structure-function analysis of the VDR protein has defined distinct domains involved in DNA binding, ligand binding, receptor dimerisation and gene transactivation, including a C-terminal activation function domain (AF-2) that is important for cofactor...
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