Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Endocrinology. 2010 Mar;151(3):886-95. doi: 10.1210/en.2009-1010. Epub 2010 Jan 5.
Without the vitamin D receptor (VDR), adult mammals develop reduced intestinal calcium absorption, rickets, and osteomalacia. Intestinal calcium absorption normally increases during pregnancy so that the mother can supply sufficient calcium to her fetuses. The maternal skeleton is rapidly resorbed during lactation to provide calcium needed for milk; that lost bone mineral content (BMC) is completely restored after weaning. We studied Vdr null mice to determine whether these adaptations during pregnancy and lactation require the VDR. Vdr nulls were severely rachitic at 10 wk of age on a normal diet. Pregnancy induced a 158% increase in Vdr null BMC to equal the pregnant wild-type (WT) value. Lactation caused BMC losses that were equal in Vdr nulls and WT. Vdr nulls recovered after weaning to a BMC 50% higher than before pregnancy and equal to WT. Additional analyses showed that during pregnancy, duodenal (45)Ca absorption increased in Vdr nulls, secondary hyperparathyroidism lessened, bone turnover markers decreased, and osteoid became fully mineralized. A genome-wide microarray analysis of duodenal RNA found marked reduction of Trpv6 in Vdr nulls at baseline but a 13.5-fold increase during pregnancy. Calbindin D-9K (S100g) and Ca(2+)-ATPase (Pmca1) were not altered by pregnancy. Several other solute transporters increased during pregnancy in Vdr nulls. In summary, Vdr nulls adapt to pregnancy by up-regulating duodenal Trpv6 and intestinal (45)Ca absorption, thereby enabling rapid normalization of BMC during pregnancy. These mice lactate normally and fully restore BMC after weaning. Therefore, VDR is not required for the skeletal adaptations during pregnancy, lactation, and after weaning.
没有维生素 D 受体 (VDR)，成年哺乳动物会出现肠道钙吸收减少、佝偻病和骨软化症。肠道钙吸收通常在怀孕期间增加，以便母亲能够为胎儿提供足够的钙。哺乳期母亲的骨骼会迅速被吸收，以提供牛奶所需的钙；断奶后，失去的骨矿物质含量 (BMC) 会完全恢复。我们研究了 Vdr 基因敲除小鼠，以确定这些在怀孕和哺乳期的适应性是否需要 VDR。在正常饮食下，10 周龄的 Vdr 基因敲除小鼠严重患有佝偻病。怀孕使 Vdr 基因敲除小鼠的 BMC 增加了 158%，与怀孕的野生型 (WT) 小鼠相当。哺乳期导致 Vdr 基因敲除小鼠和 WT 小鼠的 BMC 流失相等。断奶后，Vdr 基因敲除小鼠恢复到 BMC 比怀孕前高 50%，与 WT 小鼠相当。进一步的分析表明，在怀孕期间，Vdr 基因敲除小鼠的十二指肠 (45)Ca 吸收增加，继发性甲状旁腺功能亢进减轻，骨转换标志物减少，类骨质完全矿化。对十二指肠 RNA 的全基因组微阵列分析发现，Vdr 基因敲除小鼠的 Trpv6 在基线时明显减少，但在怀孕期间增加了 13.5 倍。钙结合蛋白 D-9K (S100g) 和 Ca(2+)-ATPase (Pmca1) 不受怀孕影响。其他几种溶质转运体在怀孕期间在 Vdr 基因敲除小鼠中增加。总之，Vdr 基因敲除小鼠通过上调十二指肠 Trpv6 和肠道 (45)Ca 吸收来适应怀孕，从而使 BMC 在怀孕期间迅速正常化。这些小鼠正常哺乳，并在断奶后完全恢复 BMC。因此，VDR 不是怀孕期间、哺乳期和断奶后骨骼适应性所必需的。
