1α,25-二羟基维生素D3-26,23-内酯及其中间代谢产物对体内和体外骨代谢的影响。

Effects of 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone and its intermediate metabolites on bone metabolism in vivo and in vitro.

作者信息

Kumegawa M, Ishizuka S, Sumitani K, Hiura K, Kawata T, Okawa M, Hakeda Y

机构信息

Department of Oral Anatomy, Meikai University School of Dentistry, Saitama, Japan.

出版信息

Contrib Nephrol. 1991;91:109-15. doi: 10.1159/000420165.

DOI:10.1159/000420165

PMID: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.

摘要

对23(S)25(R)-1α,25-(OH)₂D₃-26,23-内酯的哪种中间代谢产物导致了1α,25-(OH)₂D₃-26,23-内酯不同于1α,25-(OH)₂D₃的独特生物学功能进行了比较研究。在维生素D缺乏的大鼠中，三种中间代谢产物，即1α,25(R)26-(OH)₃D₃、1α,23(S)25(R)26-(OH)₄D₃和23(S)25(R)-1α,25-(OH)₂D₃-26,23-内醇，与1α,25-(OH)₂D₃一样，刺激了骨吸收。另一方面，1α,25-(OH)₂D₃-26,23-内酯仅抑制骨吸收。1α,25-(OH)₂D₃、1α,25-(OH)₂D₃-26,23-内酯和其他三种代谢产物以与其对1α,25-(OH)₂D₃受体的结合亲和力相关的方式刺激造血母细胞形成单核细胞。然而，从1α,25-(OH)₂D₃-26,23-内酯处理的MC3T3-E1细胞获得的条件培养基抑制单核细胞形成，这可能是由于1α,25-(OH)₂D₃-26,23-内酯处理的细胞所产生的一些抑制因子的作用，而从1α,25-(OH)₂D₃或其他代谢产物处理的MC3T3-E1细胞获得的条件培养基刺激单核细胞形成。这些事实表明，只有1α,25-(OH)₂D₃-26,23-内酯具有抑制骨吸收的作用，并且内酯环在其表达中起主要作用。