Biological Activity of 1α -Hydroxycholecalciferol, A Synthetic Analog of the Hormonal form of Vitamin D3

1,25-Dihydroxycholecalciferol, the apparent active hormonal form of cholecalciferol (vitamin D3), is formed from cholecalciferol by specific and sequential hydroxylations of the sterol at carbons 25 and 1. Recently, 1α -hydroxycholecalciferol was synthesized and we report on its biological activity...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1973-08, Vol.70 (8), p.2248-2252
Main Authors: Haussler, Mark R., Zerwekh, Joseph E., Hesse, Robert H., Rizzardo, E., Pechet, Maurice M.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences: Biochemistry
Bone metabolism
Bones
Calcium
Calcium metabolism
Cholecalciferols
Hormone metabolism
Hormones
Human resources
Sterols
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Summary:1,25-Dihydroxycholecalciferol, the apparent active hormonal form of cholecalciferol (vitamin D3), is formed from cholecalciferol by specific and sequential hydroxylations of the sterol at carbons 25 and 1. Recently, 1α -hydroxycholecalciferol was synthesized and we report on its biological activity in rachitic chicks. 1α -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 1α -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 1α -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. 1α -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 1α -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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.70.8.2248