AJP - Endocrinology and Metabolism, Vol 245, Issue 4 359-E364, Copyright © 1983 by American Physiological Society
Stimulation of 24R,25-dihydroxyvitamin D3 synthesis by metabolites of vitamin D3
G. S. Reddy, G. Jones, S. W. Kooh, D. Fraser and H. F. DeLuca
Previously we have shown that the isolated perfused kidney from vitamin
D-deficient rats converts [3H]25(OH)D3 into [3H]1 alpha,25(OH)2D3. When
certain vitamin D metabolites were added to perfusate the same kidney began
to synthesize [3H]24R,25(OH)2D3. In this study we investigated the
structural requirements of the vitamin D molecule necessary to stimulate
synthesis of [3H]24R,25(OH)2D3 in a 1-hydroxylating kidney. Kidneys were
perfused with tracer [3H]25(OH)D3 (450 pM) alone and in the presence of a
variety of hydroxylated metabolites and fluorinated analogues of vitamin D3
at concentrations of 450 pM to 25 microM. Tracer [3H]25(OH)D3 alone
resulted in synthesis of only [3H]1 alpha,25(OH)2D3 during the 6-h
perfusion period. 25-Hydroxylated metabolites [25(OH)D3, 25 nM; 1
alpha,25(OH)2D3, 25 nM; 24R,25(OH)2D3, 25 nM; 24(F)2,25(OH)D3, 50 nM]
stimulated [3H]24R,25(OH)2D3 production at 2 h of perfusion. On the other
hand, analogues without the 25-hydroxyl group [D3; 1 alpha(OH)D3; 25(F)D3;
1 alpha(OH),25(F)D3; 1 alpha(F)D3; 1 beta(F)D3]; did not stimulate
[3H]24R,25(OH)2D3 synthesis. We conclude that the 25-hydroxyl group is an
essential determinant of 24-hydroxylation.
