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Intestinal Calcium Absorption in the Aged Rat: Evidence of Intestinal Resistance to 1,25(OH)₂ Vitamin D¹

Mineral Bioavailability Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University (R.J.W., J.C.F., K.C.), Boston, Massachusetts 02111; University of Virginia Medical School (M.E.B.), Charlottesville, Virginia 22908; and the University of Wisconsin (H.D.), Madison, Wisconsin 53706

Address all correspondence and requests for reprints to: Richard J. Wood, Ph.D., Mineral Bioavailability Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, Massachusetts 02111. E-mail: wood_mb{at}hnrc.tufts.edu

We investigated the role of circulating 1,25-dihydroxycholecalciferol (1,25(OH)₂D) and intestinal resistance to 1,25(OH)₂D in the diminished intestinal calcium absorption capacity of the senescent rat. We measured plasma 1,25(OH)₂D, 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(OH)₂D, 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)₂D for up to 6 days and found that despite a marked elevation of plasma 1,25(OH)₂D 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)₂D, in a dose-response study we altered plasma 1,25(OH)2D by continuous infusion of 1,25(OH)₂D (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)₂D 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)₂D. 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)₂D and a second defect related to a relative intestinal resistance to the action of 1,25(OH)₂D, which is apparently not due to a reduction in intestinal vitamin D receptor levels.

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