DIFFERENCES IN METABOLISM BETWEEN 26,27,27,27-HEXAFLUORO-1-ALPHA,25-DIRYDROXYVITAMIN D-3 AND 1-ALPHA,25-DIHYDROXYVITAMIN D-3 IN CULTURED NEONATAL MOUSE CALVARIA

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 alph a,25-dihydroxyvitamin (1,25(OH)(2)D-3) in cultured neonatal mouse calv aria to elucidate why ST-630 is more potent than 1,25(OH)(2)D-3 in sti mulating bone resorption in organ culture. The metabolites were extrac ted with ethyl acetate or chloroform/methanol (1:1) from cultured calv aria 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 chromatogra phy. [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 equipotentl y as 1,25(OH)(2)D-3. The amount of [H-3]-ST-232 produced in the bone i ncreased with passage of the culture period. In contrast, the amount o f [H-3]-ST-630 in the bones decreased in the 2 day cultures. In the me dium, [H-3]-ST-630 was hardly detectable for 2 days. This suggests tha t ST-630 is metabolized to ST-232 which is retained in the bones. On t he other hand, some [H-3]-1,25(OH)(2)D-3 was metabolized to inactive f orms detectable in the medium. Therefore, the high potency of ST-630 i n 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 metaboli sm in the cultured bones.