title: Biological activity of 1alpha-hydroxycholecalciferol, a synthetic analog of the hormonal form of vitamin D3.
abstract: 1,25-Dihydroxycholecalciferol, the apparent active hormonal form of cholecalciferol (vitamin D(2)), is formed from cholecalciferol by specific and sequential hydroxylations of the sterol at carbons 25 and 1. Recently, 1alpha-hydroxycholecalciferol was synthesized and we report on its biological activity in rachitic chicks. 1alpha-Hydroxycholecalciferol is identical in potency to 1,25-dihydroxycholecalciferol in stimulation of intestinal calcium absorption; either sterol elicits a near maximal effect at a dose of 0.3-0.6 nmol. The time-course of action of 1alpha-hydroxycholecalciferol also parallels that of the active metabolite 1,25-dihydroxycholecalciferol with a maximal increase in calcium transport occurring 5-10 hr after administration of sterol to vitamin D-deficient chicks. 6.5 nmol of 1alpha-hydroxycholecalciferol causes a doubling in calcium absorption in only 2-3 hr, which is the most rapid physiologic response yet detected for a vitamin D-sterol. 1alpha-Hydroxycholecalciferol is active also in enhancing bone calcium resorption and, like 1,25-dihydroxycholecalciferol, is at least 10 times as active as cholecalciferol in mobilizing bone calcium and raising plasma calcium concentration. It is concluded that 1alpha-hydroxycholecalciferol represents a synthetic analog of 1,25-dihydroxycholecalciferol that can be used both to study the mechanism of action of this hormone and as a therapeutic agent in the treatment of patients with certain metabolic bone diseases.
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D002127:Calcium Isotopes; D055598:Chemical Phenomena; D002621:Chemistry; D002645:Chickens; D002762:Cholecalciferol / Q000494:pharmacology; D004100:Dihydroxycholecalciferols / Q000494:pharmacology; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D002127:Calcium Isotopes; D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D002762:Cholecalciferol; D002118:Calcium