Effects of 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone and its intermediate metabolites on bone metabolism in vivo and in vitro.
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.
Kumegawa
M
M
Department of Oral Anatomy, Meikai University School of Dentistry, Saitama, Japan.
Ishizuka
S
S
Sumitani
K
K
Hiura
K
K
Kawata
T
T
Okawa
M
M
Hakeda
Y
Y
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000502:physiology
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; C026947:1,25-dihydroxyvitamin D3-26,23-lactone; D002117:Calcitriol; D002118:Calcium