26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D
3 [F
6-1, 25-(OH)
2D
3] is more potent than 1α, 25-dihydroxyvitamin D
3 [l, 25(OH)
2D
3] in stimulating bone resorption in vitro and in vivo. The reason why F
6-1, 25(OH)2D
3 is more active remains unclear. To clarify the relationship between the bone-resorbing activity of each vitamin D
3 analogue and the metabolism of each analogue, in the present study, we used an ex vivo method that was established by Reynolds et al (
Calcif Tissue Res, 1974, 15, 333-339). The effect of F
6-1, 25(OH)
2D
3 or 1, 25(OH)
2D
3 on
45Ca release from parietal bones, prepared at 3, 14 and 24 h after injection of 1.9, 3.8, 7.6 or 15.2 pmol vitamin D analog /g body weight, was examined. F6-1, 25(OH)
2D
3 was more potent than 1, 25(OH)
2D
3 during each in vivo time period. 1, 25(OH)
2D
3 at 3h after the injection was more active compared to the control (no injection of 1, 25(OH)
2D
3), but not at 14 and 24h. The radioactivity of the bones after the injection of [
3H]-F
6-, 25(OH)
2D
3 was retained even at 24h. In the case of [
3H]-1, 25(OH)
2D
3, the radioactivity of bones decreased with an increase in the in vivo period. In a HPLC analysis of the lipid extract of bone homogenate, [
3H]-F
6-1, 25(OH)
2D
3 alone was detected at 3 h after the injection and both [
3H]-F
6-1, 25(OH)
2D
3 and [
3H]-26, 27-hexafluoro-1α, 23S, 25-trihydroxy-vitamin D
3 [F
6-1, 23, 25(OH)
3D
3] were detected at 14 and 24h after the injection. [
3H]-1, 25(OH)
2D
3 was highly detected at 3 h after the injection, but it decreased with an increase in the in vivo period. In the ex vivo test, the activity of F
6-1, 23, 25(OH)
3D
3 was less than that of F
6-1, 25(OH)
2D
3 but similar to that of 1, 25(OH)
2D
3. The present study indicates that F
6-1, 25(OH)
2D
3 is more active and more long-lasting than 1, 25(OH)
2D
3 in the ex vivo method. A higher potency of F
6-1, 25(OH)
2D
3 is explained, at least partly, by the results that the amounts of both F
6-1, 25(OH)
2D
3 and its active metabolite, F
6-1, 23, 25(OH)
3D
3, in the bones are higher than that of 1, 25(OH)
2D
3, and that F
6-1, 25(OH)
2D
3 and its metabolite are retained in bones longer than 1, 25(OH)
2D
3.
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