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 dimini shed intestinal calcium absorption capacity of the senescent rat. We m easured plasma 1,25(OH)(2)D, total and unoccupied duodenal vitamin D r eceptor, duodenal calbindin D-9k protein (calbindin D), and net dietar y 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 vitam in D receptor levels. We then measured duodenal calcium absorption fro m 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 o ld 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 th e linear regression between plasma 1,25(OH)(2)D and duodenal Ca transp ort in old rats was only 46% of that observed in young rats, suggestin g 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 def ect 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.