Differences In Metabolism Between 26,26,26,27,27,27-Hexafluoro-1-Alpha,25-Dirydroxyvitamin D-3 And 1-Alpha,25-Dihydroxyvitamin D-3 In Cultured Neonatal Mouse Calvaria
RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY(1994)
摘要
We investigated the metabolism of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D-3, (26,27-F-6-1,25(OH)(2)D-3 ST-630) and 1 alpha,25-dihydroxyvitamin (1,25(OH)(2)D-3) in cultured neonatal mouse calvaria to elucidate why ST-630 is more potent than 1,25(OH)(2)D-3 in stimulating bone resorption in organ culture. The metabolites were extracted with ethyl acetate or chloroform/methanol (1:1) from cultured calvaria or medium incubated with [H-3]-ST-630 or [H-3]-1,25(OH)(2)D-3 for various periods, and separated by high performance liquid chromatography.[H-3]-ST-630 in cultured calvaria was converted to [H-3]-26,26,26,27,27,27-hexafluro-1 alpha,23(S),25-trihydroxyvitamin D-3(26,27-F-6-1,23,25(OH)(3)D-3,ST-232), which stimulated bone resorption equipotently as 1,25(OH)(2)D-3. The amount of [H-3]-ST-232 produced in the bone increased with passage of the culture period. In contrast, the amount of [H-3]-ST-630 in the bones decreased in the 2 day cultures. In the medium, [H-3]-ST-630 was hardly detectable for 2 days. This suggests that ST-630 is metabolized to ST-232 which is retained in the bones. On the other hand, some [H-3]-1,25(OH)(2)D-3 was metabolized to inactive forms detectable in the medium.Therefore, the high potency of ST-630 in stimulating bone resorption in organ culture may be associated with a difference between ST-630 and 1,25(OH)(2)D-3 in the mode of metabolism in the cultured bones.
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关键词
cultured neonatal mouse calvaria,metabolism,d3
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