Intestinal calcium (Ca) absorption depends upon vitamin D signaling through the vitamin D receptor (VDR) in the proximal and distal intestine while lower VDR content causes intestinal resistance to 1,25 dihydroxyvitamin D (1,25(OH)2 D) action. We tested whether intestinal responsiveness to 1,25(OH)2 D is increased in mice with higher than normal VDR levels resulting from transgenic VDR expression in the whole intestine (villin promoter-human VDR transgene, HV2). Wild type (WT) and HV2 mice were treated with 0, 0.15, or 0.3 ng 1,25(OH)2 D/g body weight (BW) (n = 6/dose) for 6 h. 1,25(OH)2 D significantly induced Cyp24a1, Trpv6, and S100 g mRNA in duodenum (Dd) of WT mice but induction was not higher in HV2 mice. We next tested whether higher intestinal VDR could protect mice from the consequences of low dietary Ca intake. WT and HV2 mice were fed diets with 0.125, 0.25, 0.5 (reference), or 1% Ca from weaning to 3 months of age (n = 9/diet/genotype). Dietary Ca restriction caused a dose dependent increase in serum 1,25(OH)2 D, Dd TRPV6, and Dd S100 g mRNA in WT mice and the effect was greater in HV2 mice. While Ca absorption was increased by low Ca intake, there was no difference in Ca absorption between HV2 and WT mice. Similarly, while bone density and microstructure were reduced by low Ca intake in WT mice, high intestinal VDR in HV2 mice did not protect bone in mice fed low Ca diets. Thus, while intestinal VDR and vitamin D signaling are essential for normal Ca metabolism during growth, our data demonstrate that higher than normal intestinal VDR levels do not improve the intestinal response to either 1,25(OH)2 D injection or to elevated 1,25(OH)2 D levels resulting from the physiologic adaptation to low Ca diets.

中文翻译：

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小鼠对肠道特异性VDR的转基因表达导致更高的肠道VDR水平不能改善对1,25二羟基维生素D的肠道反应。

肠道钙（Ca）的吸收取决于近端和远端肠道中维生素D受体（VDR）的维生素D信号传导，而较低的VDR含量则引起肠道对1,25二羟基维生素D（1,25（OH）2 D）作用的抵抗力。我们测试了在整个肠道中转基因VDR表达（正常蛋白启动子-人VDR转基因，HV2）导致高于正常VDR水平的小鼠中，肠道对1,25（OH）2 D的反应性是否增加。野生型（WT）和HV2小鼠分别以0、0.15或0.3 ng 1,25（OH）2 D / g体重（BW）（n = 6 /剂量）处理6小时。1,25（OH）2 D显着诱导WT小鼠十二指肠（Dd）的Cyp24a1，Trpv6和S100 g mRNA表达，但在HV2小鼠中诱导并不更高。接下来，我们测试了较高的肠道VDR是否可以保护小鼠免受低钙摄入量的影响。从断奶至3个月大时，WT和HV2小鼠的饮食中饲喂0.125、0.25、0.5（参考）或1％Ca（n = 9 /饮食/基因型）。饮食中钙的限制导致野生型小鼠的血清1,25（OH）2 D，Dd TRPV6和Dd S100 g mRNA呈剂量依赖性增加，而在HV2小鼠中这种作用更大。虽然低钙摄入量会增加钙的吸收，但HV2和WT小鼠之间的钙吸收没有差异。类似地，虽然野生型小鼠的低钙摄入降低了骨密度和显微结构，但HV2小鼠的高肠VDR却不能保护低钙饮食的小鼠的骨骼。因此，虽然肠道VDR和维生素D信号对于生长过程中正常的Ca代谢至关重要，但我们的数据表明，高于正常肠道VDR水平并不能改善对1,25（OH）2 D注射或升高1的肠道反应。