Wood R J, Fleet J C, Cashman K, Bruns M E, Deluca H F
Mineral Bioavailability Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.
Endocrinology. 1998 Sep;139(9):3843-8. doi: 10.1210/endo.139.9.6176.
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 D9k 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 s.c. 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.
我们研究了循环中的1,25 - 二羟胆钙化醇（1,25(OH)₂D）以及肠道对1,25(OH)₂D的抵抗在衰老大鼠肠道钙吸收能力下降中所起的作用。我们测定了不同年龄大鼠的血浆1,25(OH)₂D、十二指肠维生素D受体总量及未被占据的受体量、十二指肠钙结合蛋白D9k（钙结合蛋白D）以及膳食钙净吸收量。正如预期的那样，循环中的1,25(OH)₂D、钙结合蛋白D和钙净吸收量均随年龄增长而下降。然而，肠道维生素D受体水平并未出现与年龄相关的明显变化。随后，我们在连续皮下注射1,25(OH)₂D长达6天后，测量了原位肠袢的十二指肠钙吸收情况，发现尽管血浆1,25(OH)₂D显著升高，但老年大鼠的十二指肠钙吸收仍明显低于年轻大鼠。为了评估在较宽生理范围内血浆1,25(OH)₂D水平下的钙吸收情况，我们在一项剂量反应研究中通过连续注射1,25(OH)₂D（剂量为0、4或14 ng/100 g体重/天）9天来改变血浆1,25(OH)₂D水平。我们发现，老年大鼠血浆1,25(OH)₂D与十二指肠钙转运之间线性回归的斜率仅为年轻大鼠的46%，这表明十二指肠钙转运过程存在与年龄相关的对1,25(OH)₂D激素作用的抵抗。总体而言，我们的观察结果表明老年动物维生素D代谢存在双重缺陷：一个缺陷与循环中1,25(OH)₂D水平较低有关，另一个缺陷与肠道对1,25(OH)₂D作用的相对抵抗有关，而这显然不是由于肠道维生素D受体水平降低所致。
