Pregnancy up-regulates intestinal calcium absorption and skeletal mineralization independently of the vitamin D receptor

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Bone Density
  • Calcification, Physiologic*
  • Calcitriol / metabolism
  • Calcium / metabolism*
  • Duodenum / metabolism
  • Female
  • Gene Expression Profiling
  • Homeostasis
  • Hyperparathyroidism, Secondary / metabolism
  • Intestinal Absorption*
  • Lactation / metabolism
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Pregnancy
  • Pregnancy, Animal / metabolism*
  • Receptors, Calcitriol / metabolism*
  • Rickets / metabolism
  • Rickets / pathology
  • Tibia / pathology
  • Up-Regulation


  • Receptors, Calcitriol
  • Calcitriol
  • Calcium