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Calcified Tissue International

, Volume 55, Issue 3, pp 190–197 | Cite as

Calcium regulating activity of 26,27-dimethyl analog of 24R,25-dihydroxyvitamin D3

  • T. Miyahara
  • M. Harada
  • S. Kondo
  • H. Komiyama
  • S. Matsuda
  • A. Miyanishi
  • M. Matsumoto
  • W. Xue-Ya
  • Y. Ikemoto
  • A. Sugure
  • A. Kozakai
  • T. Takamura
  • S. Higuchi
  • S. Otomo
  • Y. Chida
  • Y. Kikuchi
  • H. Kozuka
  • N. Ikekawa
Laboratory Investigations

Abstract

To determine the possibility that methyl substitution in 26- and 27-positions of 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3] alters activities of the original compound, the effects of 24,25(OH)2D3 on calcium (Ca) regulating activity were compared with those of its methyl analog [24,25(OH)2(CH3)2D3] in addition to 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 24,25(OH)2D3 at 10-6 M and 24,25(OH)2(CH3)2D3 at 10-7 M and above significantly stimulated both bone resorption in neonatal mouse calvaria cultures and formation of osteoclast-like multinucleated cells (MNC) in mouse bone marrow cultures. A stimulative effect of 1,25(OH)2D3 on bone resorption and MNC formation was recognized in very low concentrations (10-11 M and above). Although a potency of 24,25(OH)2(CH3)2D3 in stimulating bone calcium (Ca) mobilization and intestinal Ca transport was higher than that of 24,25(OH)2D3, the potencies of both compounds were similar to that of 1,25(OH)2D3 unlike in vitro experiments. As 1,24R,25-trihydroxy-26,27-dimethylvitamin D3 showed almost the same effect as 24,25(OH)2(CH3)2D3, the dihydroxy form is suggested to be hydroxylated at 1α position and converted to trihydroxy form in vitamin D-deficient rats. From these results, methyl substitution in 26- and 27-position of 24,25(OH)2D3 was found to elevate Ca regulating activity of the original compound. In addition, it is suggested that the basis for a similarity in potency between 1,25(OH)2D3 and 24,25(OH)2D3 or its dimethyl analog in vitamin D-deficient rats is likely the result of 1 α-hydroxylation.

Key words

Bone resorption Osteoclast-like cell formation Bone Ca mobilization Intestinal Ca transport 24R,25-dihydroxy-26,27-dimethylvitamin D3 

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Copyright information

© Springer-Verlag New York Inc. 1994

Authors and Affiliations

  • T. Miyahara
    • 1
  • M. Harada
    • 2
  • S. Kondo
    • 2
  • H. Komiyama
    • 1
  • S. Matsuda
    • 1
  • A. Miyanishi
    • 1
  • M. Matsumoto
    • 1
  • W. Xue-Ya
    • 1
  • Y. Ikemoto
    • 2
  • A. Sugure
    • 2
  • A. Kozakai
    • 2
  • T. Takamura
    • 2
  • S. Higuchi
    • 2
  • S. Otomo
    • 2
  • Y. Chida
    • 3
  • Y. Kikuchi
    • 3
  • H. Kozuka
    • 1
  • N. Ikekawa
    • 4
  1. 1.Department of Toxicology, Faculty of Pharmaceutical SciencesToyama Medical and Pharmaceutical UniversityToyamaJapan
  2. 2.Department of Pharmacology, Research CenterTaisho Pharmaceutical Co., Ltd.SaitamaJapan
  3. 3.Tokyo Research CenterCentral Glass Co., Ltd.SaitamaJapan
  4. 4.Department of Sciences and TechnologyIwaki Meisei UniversityIwakiJapan

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