| Summary: | Thesis (M.Sc.)--Memorial University of Newfoundland, 2010. Medicine Includes bibliographical references (leaves 86-95) Pregnancy and lactation create a large physiological demand for calcium. Normally, 1,25 dihydroxyvitamin D (1,25(OH)2D3) and the vitamin D receptor (VDR) are critical for the regulation of calcium and bone metabolism. Without 1,25(OH)2D3 and/or the VDR, intestinal calcium absorption is reduced, leading to hypocalcemia, secondary hyperparathyroidism, rickets, and osteomalacia. This project assessed whether 1,25(OH)2D3 and the VDR were required for the regulation of calcium and bone metabolism during the reproductive periods. -- Mice lacking the gene encoding for the VDR (Vdr null) and wild-type (WT) mice were raised on a regular 1% calcium diet until 10 weeks of age and then switched to a 2% calcium, 20% lactose enriched diet. Bone mineral content (BMC) was measured at baseline, late pregnancy, late lactation and 21 days after weaning. Duodenal 45Ca absorption and gene expression, parameters of calcium homeostasis, bone turnover markers and bone histomorphometry were measured at baseline and late pregnancy. -- Vdr null mice had a significantly lower BMC at baseline as compared to WT siblings. WT mice gained 7% BMC during pregnancy, lost 18% during lactation and recovered to baseline post weaning. In contrast, Vdr null sisters gained 57% BMC during pregnancy (p≤0.05) resulting in a BMC that was equal to WT. Vdr nulls lost 31% BMC during lactation and recovered post-weaning to a value that was 49% higher than the prepregnancy baseline. Duodenal 45Ca absorption and the expression of the calcium channel transient receptor potential, vanilloid type 6 (Trpv6) was lower in Vdr nulls at baseline but significantly increased to WT levels during pregnancy. Vdr null serum parathyroid hormone (PTH) levels and bone turnover were elevated at baseline but normalized to WT levels by late pregnancy. Urine calcium concentration was reduced at baseline in Vdr null mice but similar to WT values during pregnancy. Vdr null rachitic tibias were not morphologically repaired during pregnancy but had increased mineralization of osteoid. -- In summary, pregnancy increased intestinal calcium absorption in Vdr null mice, possibly through an increase in duodenal Trpv6 expression. This led to a normalizing of serum PTH levels, bone turnover and ultimately an increase in BMC. In conclusion, intestinal calcium absorption and skeletal mineralization are regulated independently of 1,25 (OH)2D3 and the VDR during pregnancy.
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