Studies on Calciferol Metabolism
نویسندگان
چکیده
The administration of cholecalciferol (vitamin D3) (CC) to rachitic chicks results in the production of two major polar metabolites, 25-hydroxycholecalciferol (25-OH-CC) and 1,25-dihydroxycholecalciferol (1,25-diOH-CC), and a number of other minor metabolites. Eighteen hours after a physiological dose (0.65 mnoles) of radioactive cholecalciferol, 80% of the radioactivity in the target intestine is present as 1,25-diOH-CC and 19% as 25-OH-CC. In the other major target organ, the skeletal system, 25% of the radioactivity is present in a form chromatographically identical to 1,25diOH-CC, 50% as 25-OH-CC and 20% as unaltered CC. 1,25-diOH-CC has been shown previously to be the probable metabolically active form of vitamin Da which initiates increased intestinal calcium transport. 1,25-diOH-CC stimulated increased bone calcium mobilization, as measured by serum calcium elevation, in both vitamin D deficient chicks and rats. 1,25-diOH-CC initiates maximal bone calcium mobilization more rapidly than either CC or 25-OH-CC; maximal activity occurs at 8 to 10 hours for 1,25-diOH-CC and at 20 to 24 hours for the other steroids. When the maximal biological activity of 1,25diOH-CC observed at 9 hours is compared to the maximal activity obtained by the other steroids at 24 hours, it was determined that 1,25-diOH-CC is 5.5 times more active than CC and 3.6 times more active than 25-OH-CC in stimulating bone calcium mobilization. Following administration of 1 ,25-diOH[3H]CC, maximal localization of radioactivity in the bone tissue occurred after only 1 to 2 hours. This radioactivity was found by chromatographic analysis to be unaltered 1,25-diOH-CC. There is an obligatory requirement for the kidney mediated hydroxylation of 25-OH-CC to occur prior to the development of a biological response. Administration of 3.25 mnoles of CC, 3.25 nmoles of 25-OH-CC, 3.25 nmoles of dihydrotachystero13, and 0.26 mnoles of 1,25-diOH-CC all produced bone
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