The biological activities of several 24-oxo and 26,23-lactone metabolites of vitamin D were determined in bone organ cultures. The 24-oxo metabolites were significantly more potent bone-resorbing agents than the lactones. 1,25-(OH)2-24-oxo-D3 had 0.18× the bone-resorbing activity of 1,25-(OH)2D3 in fetal rat limb bones and was equipotent with 1,25-(OH)2D3 in neonatal mouse calvaria. In the limb bone system, 1,23,25-(OH)3-24-oxo-D3 had 0.08× the activity of 1,25-(OH)2D3. 1,25-(OH)2D3 and 1,25-(OH)2-24-oxo-D3 had a similar time course of bone-resorbing effects in both bone culture systems. The most potent of the lactones, 1,25S-(OH)2D3-26,23R-lactone, had approximately 0.009× the activity of 1,25-(OH)2D3 and approximately 500 times the activity of the 25S-OH-D3-26,23R-lactone. The 25S and 1,25S lactones were more potent than the 25R and 1,25R isomers. In experiments designed to determine whether either 1,25-(OH)2-24-oxo-D3 or 25R-OH-D3-26,23S-lactone could prevent the bone-resorbing activity of 1,25-(OH)2D3, no inhibitory effects were observed. The results suggest that conversion to the lactones represents a substantial inactivation step, whereas conversion to 24-oxo-derivatives results in less reduction in biological activity.
ASJC Scopus subject areas
- Molecular Biology