Modulation of Renal Production of 24,25- and 1,25- Dihydroxyvitamin D3in Young and Adult Rats by Dietary Calcium, Phosphorus, and 1,25-Dihydroxyvitamin D3

Abstract

The purpose of this study was to examine the effects of dietary calcium (Ca), phosphorus (P), and vitamin D3 metabolites on the renal metabolism of 25-hydroxyvitamin D3 (25OHD3) to either 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] in the rat. The regulation of 25OHD3 metabolism was studied in both young and adult rats, since previous studies have suggested a change in the renal metabolism of 25OHD3 with age. Renal 25OHD3 metabolism was measured in vitro by incubating renal cortical slices with tritiated 25OHD3 and quantifying tritiated metabolites by high pressure liquid chromatography. The apparent Michaelis constant for the conversion of 25OHD3 to 1,25-(OH)2D3 in this system was 1.16 microM. Experiments were conducted in rats fed a vitamin D-deficient diet containing either 0.02% Ca (low Ca) or 1.20% Ca (high Ca) for 4 weeks. Young rats (4 weeks old) fed the low Ca diet demonstrated a 2.8-fold increase in 1,25-(OH)2D3 production, but no change in 24,25-(OH)2D3 production compared to young rats fed the high Ca diet. Adult rats (12 months old) fed the low Ca diet showed no change in 1,25-(OH)2D3 production, but exhibited a decrease in 24,25-(OH)2D3 production compared to adult rats fed the high Ca diet. Repletion of the young rats fed the low Ca diet with 1,25(OH)2D3 resulted in a marked decrease in 1,25-(OH)2D3 production and an increase in 24,25-(OH)2D3 production. Repletion of the adult rat resulted in no change in 1,25-(OH)2D3 production, but a significant increase in 24,25-(OH)2D3 production. When young rats were fed diets containing various levels of Ca and P, it was found that 1,25-(OH)2D3 production was inversely correlated with plasma Ca over the range 4--13 mg/dl. Since the plasma Ca level of the adult rat was 11-12 mg/dl regardless of diet, this high concentration may explain the lack of 1,25-(OH)2D3 production observed in the adult.