Development-related regulation of plasma 1,25(OH)2D3 concentration by calcium intake in rat pups

Circulating 1,25(OH)2D3 was determined in female rats between ages 1 and 20 weeks and in male rats between ages 5 and 12 weeks while the rats consumed diets containing vitamin D (5 U/g diet) and calcium concentrations of either 0.04, 0.4 or 1.6% Ca. When consuming the 0.4% Ca diet female rats had mean (+/- SE, pg/ml) serum 1,25(OH)2D3 values of 45 +/- 7 at 2 weeks, 272 +/- 23 at 4 weeks, 221 +/- 18 at 5 weeks and 51 +/- 6 and 49 +/- 4 at 13 and 20 weeks, respectively. Circulating 1,25 (OH)2D3 levels in the males at 4.5, 8 and 12 weeks were insignificantly higher than the levels for the females at comparable ages. There were no significant changes in plasma calcium over the ages examined in either sex. In order to test the efficiency of regulation of circulating 1,25(OH)2D3, 3-week-old female rats were given the 0.04% Ca diet for 2 or 6 weeks. At ages 5 and 9 weeks, serum 1,25(OH)2D3 values were 640 +/- 82 and 604 +/- 39 pg/ml, respectively, and therefore at least 3-fold higher than the values in rats consuming the 0.4% Ca diet. Plasma Ca concentrations in the calcium-deprived rats were 8.7 +/- 0.2 and 6.5 +/- 0.1 at 5 and 9 weeks, respectively. When the 0.04% Ca diet was introduced at 5 weeks of age, plasma Ca fell only 0.5 mg/dl and plasma 1,25(OH)2D3 rose to 1265 +/- 48 pg/ml. In contrast, plasma 1,25(OH)2D3 rose to only 176 +/- 19 pg/ml and plasma Ca fell 0.5 mg/dl when 12-week-old rats were given the 0.04% Ca diet for 5 weeks. When suckling rats were given access to the 1.6% Ca diet and continued to consume this diet after weaning, circulating 1,25(OH)2D3 concentrations were approximately one half the value of the rats consuming the 0.4% Ca diet at 3,4,5 and 6 weeks. We conclude that rats have a biphasic serum 1,25(OH)2D3 curve between the ages of 2 and 16 weeks regardless of the dietary calcium content. Circulating plasma 1,25(OH)2D3 is regulated by dietary calcium as early as the third week of life, before weaning. We suggest that the high serum 1,25(OH)2D3 concentrations are due to increased 1 alpha-OHase activity. However, the factor(s) responsible for changes in the 1 alpha-OHase remain(s) unknown, since plasma Ca does not change, and since the plasma level of other regulators of 1,25(OH)2D3, such as phosphate and parathyroid hormone do not correlate with 1,25(OH)2D3.