Metabolism of 1,25-dihydroxycholecalciferol in the rat

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Abstract

Administration of 60 pmoles of 1,25-dihydroxycholecalciferol to vitamin D-deficient rats on a low calcium diet gives a maximal intestinal calcium transport response in 7 hr and a maximal bone calcium mobilization response in 12 hr. During the 48 hr after injection of radioactive 1,25-dihydroxycholecalciferol, unchanged 1,25-dihydroxycholecalciferol accounts for 71-98% of the radioactivity found in the intestine with minor amounts appearing in more polar metabolites. In the bone, for the 1st 12 hr, 1,25-dihydroxycholecalciferol is the major form (75-82%) present while at 24 hr, the amount of 1,25-dihydroxycholecalciferol decreases with a corresponding rise in the amounts of metabolites both less polar and more polar than the 1,25-dihydroxycholecalciferol. Since these metabolies are at their highest concentration when bone calcium mobilization is decreasing, they are most likely not responsible for the calcium mobilization observed during the 1st 12 hr. The appearance of water-soluble radioactivity in the kidney, plasma, liver, and muscle 24 hr after 1,25-dihydroxycholecalciferol injection has been demonstrated. The present results suggest that, although 1,25-dihydroxycholecalciferol is converted to further metabolites in the rat, it is probably the form of vitamin D responsible for initiating intestinal calcium transport and bone calcium mobilization.

Authors

Charles A. Frolik, Hector F. DeLuga