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1 2002

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Kroszczyński W., Morzycka B., Morzycki J.W.

Wiadomości Chemiczne

2002

[Z] 56, 9-10

793-809

The existence of vitamin D was discovered as a consequence of human disease. Vitamin D deficiency in childhood produces rickets, which is characterized by inadequate calcification of cartilage and bone. In rickets, the whole bony structure is soft and flexible, so that can hardly support the superposed weight of the body. Rickets was common in the 19th century, when the industrial revolution caused change of an agrarian society to an industrial society. The population in large measure spent much more time inside buildings, which shielded them from ultraviolet light. It was proved that sun light and cod liver oil are equally active in preventing and curing rickets. Further studies led to the discovery of an anti-rachitic vitamin D. A deficiency in vitamin D impairs bone formation in growing animals. The precursor of cholecalciferol (vitamin D3) is 7-dehydrocholesterol (provitamin D3) present in the skin. Irradiation of this compound results in the formation of previtamin D3, which spontaneously isomerizes to vitamin D3 (thermal rearrangement). Vitamin D3 is further converted by enzymatic hydroxylation reactions occurring in the liver and kidneys into an active hormone, which was isolated and identified as 1a,25-dihydroxyvitamin D3. Other biologically active metabolites and analogues of vitamin D were also described. The vitamin D endocrine system was primarily recognized for its critical role in calcium and phosphorus homeostasis. The active form of the vitamin, 1a,25-(OH) 2D3, acts on the intestine, bone, and kidney to increase serum levels of these two elements. Receptors for 1a,25-(OH) 2D3 have also been detected in a wide variety of target tissues and cell types, which are not involved in the calcemic activity. The non-classical actions of 1a,25-(OH) 2D3 have suggested a multitude of potential therapeutic applications of the vitamin D hormone for the treatment of hyperproliferative disorders (e.g. cancer and psoriasis), immune dysfunction and endocrine disorders. A number of new drugs based on the vitamin D analogues has been recently introduced to the pharmaceutical market. The story of vitamin D is not finished yet.