|Zimmerman, Duane - IOWA STATE UNIV., AMES|
|Knutson, Joyce - BONE CARE INT., WI|
|Bishop, Charles - BONE CARE INT., WI|
Submitted to: American Society for Bone and Mineral Research
Publication Type: Abstract Only
Publication Acceptance Date: December 1, 1998
Publication Date: N/A
Technical Abstract: Horst et al. evaluated C24 hydroxylation as a possible activation pathway for vit D2 in rats. In their experiments they showed that 24-D2 and 1,24-D ld be detected in vit D deficient rats receiving physiological doses (100 IU/d) of vit D2. They also showed that when given individually to vit D deficient rats as a single i.p. dose, 24-D2, 25-D2 and 25-D3 appeared to be 1-hydroxylated with the same efficiency as was demonstrated by the very similar plasma concentrations of 1,24-D2, 1,25-D2, and 1,25-D3. ever, when presented simultaneously as a single i.p. dose, 24-D2 was less efficiently 1-hydroxylated than either 25-D2 or 25-D3 as illustrated by the lower concentrations of circulating 1,24-D2 relative to 1,25-D2 and 1,25-D3. The present study was designed to evaluate the ability of 24-D2 and 25-D2 to give rise to their respective 1-hydroxylated metabolites, i.e. 1,24-D2 and 1,25-D2, when chronically administered individually to normal vit D3 replete rats. Structural analysis for each metabolite was conducted using NMR, UV and infrared spectroscopy. The results of experiments demonstrated that chronic dosing (5 ug/d for 14 d) of 25-D2 resulted in a significant increase in plasma 1,25-D2 from 9 pg/ml to 138 pg/ml which was attended by a similar decline in plasma 1,25-D3 from 193 pg/ml to 48 pg/ml. Similar chronic dosing of 24-D2, however, resulted in a minor elevation in plasma 1,24-D2 and was accompanied by a substantial decline in plasma 1,25-D3 from 193 to 75 pg/ml. These results suggest that chronic 24-D2 dosing results in reducing plasma total 1-hydrox d metabolites. The exact mechanism and possible physiological ramifications of this 24-D2 effect are unclear at this time. Body weight and plasma Ca and P were unaffected by any of the treatments.