Intestinal calcium absorption in the aged rat:: Evidence of intestinal resistance to 1,25(OH)2 vitamin D

We investigated the role of circulating 1,25-dihydroxycholecalciferol (1,25(OH)(2)D) and intestinal resistance to 1,25(OH)(2)D in the diminished intestinal calcium absorption capacity of the senescent rat. We measured plasma 1,25(OH)(2)D, total and unoccupied duodenal vitamin D receptor, duodenal calbindin D-9k protein (calbindin D), and net dietary calcium absorption in rats at several ages. As expected, circulating 1,25(OH2)(2)D, calbindin D, and net calcium absorption decreased with age. However, no age-related changes were evident in intestinal vitamin D receptor levels. We then measured duodenal calcium absorption from in situ intestinal loops after continuous sc infusion of 1,25(OH)(2)D for up to 6 days and found that despite a marked elevation of plasma 1,25(OH)(2)D duodenal calcium absorption was significantly lower in old compared with young rats. To assess calcium absorption over a wide physiological range of plasma 1,25(OH)(2)D in a dose-response study we altered plasma 1,25(OH)2D by continuous infusion of 1,25(OH)(2)D (at 0, 4, or 14 ng/100 g BW/day) for 9 days. We found that the slope of the linear regression between plasma 1,25(OH)(2)D and duodenal Ca transport in old rats was only 46% of that observed in young rats, suggesting an age-related resistance of the duodenal calcium transport process to the hormonal action of 1,25(OH)(2)D. Collectively, our observations suggest a dual defect in vitamin D metabolism in old animals: one defect related to the low circulating levels of 1,25(OH)(2)D and a second defect related to a relative intestinal resistance to the action of 1,25(OH)(2)D, which is apparently not due to a reduction in intestinal vitamin D receptor levels.