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.