Abstract
Bone-resorbing activities of 24-epi-1α-hydroxyvitamin D2 [24-epi-1α(OH)D2], 24-epi-1α,25-dihydroxyvitamin D2 [24-epi-1,25(OH)2D2], and 1α,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-1α(OH)D2 was similar to that of 1α-hydroxyvitamin D3 [1α(OH)D3] at 10-9 M-10-6 M. The activity of 24-epi-1,25(OH)2D2 was weaker than that of 1α,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-1α(OH)D2 was weaker than that of 1α(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-1α(OH)D2. In an in vivo/in vitro bone resorption test, the activity of 24-epi-1α(OH)D2 was almost similar to those of 1α(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-1α-(OH)D2 and 1α(OH)D3 were longer lasting than 24-epi-1,25(OH)2D2 and 1,25(OH)2D3 in this experiment. These results suggested that 24-epi-1α(OH)D2 as well as 1α(OH)D3 was converted into dihydroxy form in vivo.
Similar content being viewed by others
References
Ikekawa N (1987) Structures and biological activities of vitamin D metabolites and their analogs. Med Res Rev 7:333–336
Tanaka Y, Sicinski RR, DeLuca HF, Ikekawa N (1986) Unique rearrangement of ergocalciferol side chain in vitro: production of a biologically highly active homologue of 1,25-dihydroxyvitamin D3. Biochemistry 25:5512–5518
Sicinski RR, Tanaka Y, Schnoes HK, DeLuca HF (1985) Synthesis of 1α,25-dihydroxyvitamin D2, its 24 epimer and related isomers, and their binding affinity for the 1,25-dihydroxyvitamin D3 receptor. Bioorg Chem 13:158–169
DeLuca HF, Sicinski RR, Tanaka Y, Stern PH, Smith CM (1988) Biological activity of 1,25-dihydroxyvitamin D2 and 24-epi-1,25-dihydroxyvitamin D2. Am J Physiol 254:E402-E406
Perlman KL, Schnoes HK, Deluca HF (1989) A convenient synthesis of (24S)-1α-hydroxyvitamin D2. J Chem Soc Chem Commun: 1113–1115
Reynolds JJ, Holick MF, DeLuca HF (1974) The effects of vitamin D analogues on bone resorption. Calcif Tissue Res 15: 333–339
Shigeno C, Yamamoto I, Dokoh S, Hino M, Aoki J, Yamada K, Morita R, Kaneyama M, Torizuka K (1985) Identification of 1,24(R)-dihydroxyvitamin D3-like bone resorbing lipid in a patient with cancer-associated hypercalcemia. J Clin Endocrinol Metab 61:761–768
Takahashi N, Yamana H, Yoshiki S, Poodman GD, Munday GR, Jones ST, Boyde A, Suda T (1988) Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology 122:1373–1382
Burstone MS, (1958) Histochemical demonostration of acid phosphatase with naphthol AS-phosphates. J Natl Cancer Inst 21: 523–539
Reynolds JJ (1974) The role of 1,25-dihydroxycholecalciferol in bone metabolism. Biochem Soc Spec Publ 3:91–102
Fukushima M, Suzuki Y, Tohira Y, Matsunaga I, Ohi K, Nagano H, Nishii Y, Suda T (1975) Metabolism of 1α-hydroxyvitamin D3 to 1α,25-dihydroxyvitamin D3 in perfused rat liver. Biochem Biophys Res Commun 66:632–638
Reinhardt TA, Ramberg CF, Horst RL (1989) Comparison of receptor binding, biological activity, and in vivo tracer kinetics for 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and its 24 epimer. Arch Biochem Biophys 273:64–71
Stern PH, Mavreas T, Trummel CL, Schnoes HK, DeLuca HF (1976) Bone-resorbing activity of analogues of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol: effects of side chain modification and stereoisomerization on responses of fetal rat bones in vitro. Mol Pharmacol 12:879–886
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yokoyama, K., Miyahara, T., Matsumoto, M. et al. Bone-resorbing activities of 24-epi-1α-hydroxyvitamin D2 and 24-epi-1α,25-dihydroxyvitamin D2 . Calcif Tissue Int 56, 49–53 (1995). https://doi.org/10.1007/BF00298744
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00298744