Biological Activity of the Vitamin D Metabolite 1,25-Dihydroxycholecalciferol in Chickens and Rats

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Abstract
The biological activity of the vitamin D2 metabolite 1,25-dihydroxycholecalciferol was assessed in three experiments in the chick and two experiments in the rachitic rat. In the official rat line test 1,25-dihydroxycholecalciferol was found to be equally as active as an equivalent dose of cholecalciferol. Doses of 20 to 250 pmoles (0.01 to 0.10 µg) of 1,25-dihydroxy-[26,27-2H] cholecalciferol or standard amounts of cholecalciferol were fed daily to White Leghorn cockerels for 3 weeks after hatching. The following vitamin D-related responses were measured: a) the rate of growth; b) intestinal transport of test doses of 45Ca2+ in vivo and c) in vitro; d) percentage bone ash; e) serum calcium elevation. For each of these assays the 1,25-dihydroxycholecalciferol was judged to be “much more active” a) “more active” (b,d), and “as active” (c,e), as the parent cholecalciferol, where “much more active” is a response 2 to 4 times and “more active” is a response 1 to 2 times that obtained with an equivalent dose of cholecalciferol. In some instances (d,e), the relative increment of response mediated by 1,25-dihydroxycholecalciferol was greater at the low dose level (20 pmoles/day) than at a higher dose level (100 pmoles/day). The relative activity determination of 1,25-dihydroxycholecalciferol, obtained after daily administration, in comparison with cholecalciferol was markedly less than that previously obtained when the activity of single doses of these steroids were analyzed. A single dose of 1,25-dihydroxycholecalciferol was 4.4 ± 1.1 (se) [Science 171: 79 (1971)] times as effective as cholecalciferol in stimulating the intestinal absorption of Ca2+, and 5.5 ± 1.4 (se) [J. Biol. Chem. 247: 5728 (1972)] times as effective as cholecalciferol in stimulating serum Ca2+ elevation. These results collectively support the concept that 1,25-dihydroxycholecalciferol is the most highly potent form of Vitamin D3 yet known.