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  • Title: Effects of 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone and its intermediate metabolites on bone metabolism in vivo and in vitro.
    Author: Kumegawa M, Ishizuka S, Sumitani K, Hiura K, Kawata T, Okawa M, Hakeda Y.
    Journal: Contrib Nephrol; 1991; 91():109-15. PubMed ID: 1666030.
    Abstract:
    Which intermediate metabolite of 23(S)25(R)-1 alpha,25-(OH)2D3-26,23-lactone causes the unique biological functions of 1 alpha,25-(OH)2D3-26,23-lactone different from that of 1 alpha,25-(OH)2D3 was examined comparatively. The three intermediate metabolites, 1 alpha,25(R)26-(OH)3D3, 1 alpha,23(S)25(R)26-(OH)4D3, and 23(S)25(R)-1 alpha,25-(OH)2D3-26,23-lactol stimulated bone resorption, as 1 alpha,25-(OH)2D3 did, in vitamin D-deficient rats. On the other hand, 1 alpha,25-(OH)2D3-26,23-lactone only inhibited bone resorption. 1 alpha,25-(OH)2D3, 1 alpha,25-(OH)2D3-26,23-lactone and the other three metabolites stimulated MNC formation from hematopoietic blast cells in a manner correlated with their binding affinities for the 1 alpha,25-(OH)2D3 receptor. However, CM obtained from 1 alpha,25-(OH)2D3-26,23-lactone-treated MC3T3-E1 cells inhibited MNC formation, probably by the action of some inhibitory factors elaborated by the cells treated with 1 alpha,25-(OH)2D3-26,23-lactone, whereas CM obtained from 1 alpha,25-(OH)2D3 or other metabolite-treated MC3T3-E1 cells stimulated MNC formation. These facts indicate that only 1 alpha,25-(OH)2D3-26,23-lactone has an inhibitory action of bone resorption and that the lactone ring plays a major part in its expression.
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