Memorial University DAI: Vitamin D-independent regulation of intestinal calcium absorption and skeletal mineralization during pregnancy

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Title	Vitamin D-independent regulation of intestinal calcium absorption and skeletal mineralization during pregnancy
Author	Fudge, Neva Jennifer, 1985-
Description	Thesis (M.Sc.)--Memorial University of Newfoundland, 2010. Medicine
Date	2010
Pagination	xii, 112 leaves : col. ill.
Subject	Absorption (Physiology); Bones--Metabolism--Endocrine aspects; Calcium--Metabolism--Regulation; Obstetric endocrinology; Vitamin D;
Subject.MESH	Bone mineralization; Intestinal absorption; Bone and Bones--metabolism; Calcium--metabolism; Lactation--physiology; Pregnancy--physiology; Dihydroxycholecalciferols; Receptors, Calcitriol;
Degree	M.Sc.
Degree Grantor	Memorial University of Newfoundland. Faculty of Medicine
Discipline	Medicine
Language	Eng
Notes	Includes bibliographical references (leaves 86-95)
Abstract	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.
Type	Text
Resource Type	Electronic thesis or dissertation
Format	Image/jpeg; Application/pdf
Source	Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries
Local Identifier	a3301869
Rights	The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
Collection	Electronic Theses and Dissertations
Scanning Status	Completed
PDF File	(15.22 MB) -- http://collections.mun.ca/PDFs/theses/Fudge_NevaJennifer.pdf
CONTENTdm file name	175169.cpd