Abstract
High-pressure liquid chromatography capable of resolving all known vitamin D metabolites and a sensitive competitive binding protein assay specific for 1α,25-dihydroxyvitamin D 3 were used to assay the blood of rats dosed with ethanol, 1α-hydroxyvitamin D 3, 24 R-hydroxy-25-fluorovitamin D 3, or 1α-hydroxy-25-fluorovitamin D 3. Compared to the ethanoldosed animals, the blood of rats dosed with 1α-hydroxyvitamin D 3 had increased levels of 1α,25-dihydroxyvitamin D 3; but those dosed with the fluorinated vitamins did not. Instead, their blood contained a compound that cochromatographs with 1α,24 R-dihydroxyvitamin D 3 on high-pressure liquid chromatography and binds to the 1,25-dihydroxyvitamin D 3 receptor proteins. 1α,24 R-Dihydroxyvitamin D 3 binds as well as 1α, 25-dihydroxyvitamin D 3 to the chick-intestinal cytosol receptor protein for 1α,25-dihydroxyvitamin D 3; whereas 1α,24 S-dihydroxyvitamin D 3 binds only one-tenth as well as 1α,25-dihydroxyvitamin D 3. Thus it appears that in vivo, the fluorinated vitamin D compounds are converted to a compound likely to be 1α,24 R-dihydroxy-25-fluorovitamin D 3 and that may rival the potency of 1α,25-dihydroxyvitamin D 3.
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