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Endocrinology, Vol 127, 695-701, Copyright © 1990 by Endocrine Society

ARTICLES

Biological activity assessment of 1 alpha,25-dihydroxyvitamin D3-26,23- lactone and its intermediate metabolites in vivo and in vitro

S Ishizuka, K Sumitani, K Hiura, T Kawata, M Okawa, Y Hakeda and M Kumegawa
Teijin Institute for Bio-Medical Research, Tokyo, Japan.

The biological activity of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], 23(S)25(R)-1 alpha,25(OH)2D3-26,23-lactone, and three intermediate metabolites of the lactone in vivo and in vitro was comparatively examined. 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 increases, as did 1 alpha,25(OH)2D3, in intestinal calcium transport and serum calcium level in vitamin D-deficient rats fed a low-calcium diet. On the other hand, 23(S)25(R)-1 alpha,25(OH)2D3-26,23-lactone increased the calcium transport but decreased the serum calcium level. 1 alpha,25(OH)2D3,23(S)25(R)-Lactone and the other three metabolites stimulated multinucleate cell formation from hematopoietic blast cells in a manner correlated with their binding affinities for the 1 alpha,25(OH)2D3 receptor. But 23(S)25(R)-lactone did not show any inhibitory effect on the multinucleate cell formation induced by 1 alpha,25(OH)2D3 in contrast to the results obtained from unfractionated marrow cultures. Conditioned medium obtained from 23(S)25(R)-lactone- treated MC3T3-E1 cells inhibited the formation, probably by the action of some inhibitory factors elaborated by the cells treated with the lactone, whereas conditioned medium obtained from 1 alpha,25(OH)2D3 or other metabolite-treated MC3T3-E1 cells stimulated the formation. These findings suggest that 23(S)25(R)-1 alpha,25(OH)2D3-26,23-lactone might inhibit bone resorption through an inhibition of osteoclastic cell formation and that other vitamin D3 metabolites stimulate bone resorption by development of new osteoclastic cells in addition to indirect osteoclast activation.


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E. Ochiai, D. Miura, H. Eguchi, S. Ohara, K. Takenouchi, Y. Azuma, T. Kamimura, A. W. Norman, and S. Ishizuka
Molecular Mechanism of the Vitamin D Antagonistic Actions of (23S)-25-Dehydro-1{alpha}-Hydroxyvitamin D3-26,23-Lactone Depends on the Primary Structure of the Carboxyl-Terminal Region of the Vitamin D Receptor
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 J. Biol. Chem.Home page
D. Miura, K. Manabe, K. Ozono, M. Saito, Q. Gao, A. W. Norman, and S. Ishizuka
Antagonistic Action of Novel 1alpha ,25-Dihydroxyvitamin D3-26,23-lactone Analogs on Differentiation of Human Leukemia Cells (HL-60) Induced by 1alpha ,25-Dihydroxyvitamin D3
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