Metabolism and molecular mechanism of action of vitamin D: 1981.
Cholecalciferol must be regarded as a pro-hormone rather than a vitamin, since it is normally produced in skin under the influence of ultraviolet light. Cholecalciferol must be metabolized in liver to 25-hydroxycholecalciferol and subsequently to 1,25-dihydroxycholecalciferol before it can act on intestine, bone and kidney to provide calcium and phosphorus for bone mineralization and neuromuscular activity. 1,25-Dihydroxycholecalciferol is metabolized in liver and intestine to a C-23-carboxylic acid that is inactive, 25-Hydroxycholecalciferol is metabolized to a variety of metabolic products, including 23S,25-dihydroxycholecalciferol, 23S,25R-25-hydroxycholecalciferol-26,23-lactone, 24R,25-dihydroxycholecalciferol and 25,26-dihydroxycholecalciferol. These metabolites are not involved in the known actions of vitamin D. 1,25-Dihydroxycholecalciferol localizes in the nuclei of target organs through a receptor mechanism. It is believed to initiate transcription of DNA that codes for calcium and phosphorus transport proteins, the nature of which is undetermined. Production of 1,25-dihydroxycholecalciferol is stimulated by low plasma calcium through parathyrin and by low plasma phosphorus. During pregnancy and lactation, 1,25-dihydroxycholecalciferol levels are greatly increased to meet calcium demands. However, vitamin D is not absolutely essential for reproduction. It is likely that some other hormone, possibly prolactin, functions at these periods to mobilize calcium. The clinical application of the vitamin D hormone and its analogues to the treatment of bone disease is presented to illustrate the application of basic science to medical practice. Evidence for each of these points is presented.
D000328:Adult; D000818:Animals; D001842:Bone and Bones / Q000502:physiology; D002112:Calcifediol; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D002648:Child; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000188:drug therapy; D004100:Dihydroxycholecalciferols / Q000378:metabolism; D006801:Humans; D006887:Hydroxycholecalciferols / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D010018:Osteomalacia / Q000209:etiology; D051381:Rats; D012279:Rickets / Q000209:etiology; D012867:Skin / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000503:physiopathology
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D014807:Vitamin D; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium