Bone-resorbing activities of 24-epi-1 alpha-hydroxyvitamin D2 and 24-epi-1 alpha,25-dihydroxyvitamin D2.
Bone-resorbing activities of 24-epi-1 alpha-hydroxyvitamin D2 [24-epi-1 alpha(OH)D2], 24-epi-1 alpha,25-dihydroxyvitamin D2 [24-epi-1,25(OH)2D2], and 1 alpha,24S,25-trihydroxyvitamin D2 [1,24S,25(OH)3D2], which might be a metabolite of 24-epi-1,25(OH)2D2, were investigated. In an in vitro bone resorption test, the activity of 24-epi-1 alpha(OH)D2 was similar to that of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] at 10(-9) M-10(-6) M. The activity of 24-epi-1,25(OH)2D2 was weaker than that of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] at 10(-11) M-10(-8) M. On the other hand, the activity of 1,24S,25(OH)3D2 was similar to that of 24-epi-1,25(OH)2D2 at 10(-11) M-10(-9) M. In the formation assay of osteoclast-like cells, the activity of 24-epi-1 alpha(OH)D2 was weaker than that of 1 alpha(OH)D3 at 10(-7) M. The activity of 24-epi-1,25(OH)2D2 was almost similar to that of 1,25(OH)2D3 at 10(-11) M-10(-7) M. The activity of 1,24S,25(OH)3D2 was significantly weaker than that of 24-epi-1,25(OH)2D2 at 10(-11) M-10(-9) M. In the two experiments, the potencies of 24-epi-1,25(OH)2D2 were about 100 times higher than those of 24-epi-1 alpha(OH)D2. In an in vivo/in vitro bone resorption test, the activity of 24-epi-1 alpha(OH)D2 was almost similar to those of 1 alpha(OH)D3 and 1,25(OH)2D3 and higher than those of 24-epi-1,25(OH)2D2 and 1,24S,25(OH)3D2. 24-epi-1 alpha-(OH)D2 and 1 alpha(OH)D3 were longer lasting than 24-epi-1,25(OH)2D2 and 1,25(OH)2D3 in this experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
Yokoyama
K
K
Department of Toxicology, Hikone Research Laboratories, Maruho Co., Ltd., Shiga, Japan.
Miyahara
T
T
Matsumoto
M
M
Hashimoto
K
K
Komiyama
H
H
Miyanishi
A
A
Kotera
N
N
Maruyama
F
F
Kozuka
H
H
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004872:Ergocalciferols / Q000494:pharmacology*; D006887:Hydroxycholecalciferols / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology
D004872:Ergocalciferols; D006887:Hydroxycholecalciferols; C048827:1,24,25-trihydroxyergocalciferol; C042533:1 alpha-hydroxyergocalciferol; C003564:1,25-dihydroxyergocalciferol; D002117:Calcitriol; D002118:Calcium; C008088:alfacalcidol