NONCALCEMIC ACTIONS OF 1,25-DIHYDROXYVITAMIN D-3 AND CLINICAL-APPLICATIONS

Vitamin D is absolutely essential for the maintenance of a healthy skeleton, Without vitamin D, children develop rickets and adults exacerbate their osteoporosis and develop osteomalacia, Casual exposure to sunlight is the major source of vitamin D for most people, During exposure to sunlight, ultraviolet B photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D-3. Previtamin D-3 undergoes a thermal isomerization to form vitamin D-3. Increased skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can have a marked influence on the cutaneous production of vitamin D-3, Once vitamin D-3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. It is now recognized that a wide variety of tissues and cells, both related to calcium metabolism and unrelated to calcium metabolism, are target sites for 1,25(OH)(2)D-3. 1,25(OH)(2)D-3 stimulates intestinal calcium absorption and mobilizes stem cells to mobilize calcium stores from bone, Noncalcemic tissues that possess receptors for 1,25(OH)(2)D-3 respond to the hormone in a variety of ways, Of great interest is that 1,25(OH)(2)D-3 is a potent antiproliferative and prodifferentiation mediator, As a result, 1,25(OH)(2)D-3 and its analogs have wide clinical application in such diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of the breast, prostate, and colon; some leukemias and myeloproliferative disorders; chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases like psoriasis and ichthyosis.