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Document Description
TitleCalcitonin modulates skeletal mineral loss during lactation through interactions in mammary tissue and directly through osteoclasts in bone
AuthorWoodrow, Janine P.
DescriptionThesis (Ph.D.)--Memorial University of Newfoundland, 2009. Medicine
Date2009
Paginationxviii, 227 leaves : ill. (chiefly col.)
SubjectBone densitometry; Calcitonin--Physiological effect; Lactation--Nutritional aspects; Mice--Reproduction; Minerals in the body; Bone Density--physiology; Calcitonin; Lactation--physiology; Mice;
DegreePh.D.
Degree GrantorMemorial University of Newfoundland. Faculty of Medicine
DisciplineMedicine
LanguageEng
NotesIncludes bibliographical references (leaves 189-210)
AbstractThe physiological role of calcitonin in mammals has been in question since it discovery. Many have speculated that the calcitonin/calcitonin gene-related peptide (ctcgrp) gene has endured simply because of its alternate mRNA pathway to produce calcitonin gene-related peptide-cx (CGRP-cx) in neural tissue. Nevertheless, a few studies have persisted in suggesting that mammalian calcitonin is vital in times of increased calcium demand, such as during lactation. Unfortunately, these surgical based studies were fraught with experimental problems stemming from lack of true absence of calcitonin and confounding effects of thyroid ablation. This doctoral work, therefore, was carried out to test the theses that: calcitonin is required physiologically during lactation to protect the maternal skeleton against excessive resorption of mineral and that lactational bone losses in the absence of calcitonin involve a complex physiological circuitry between the breast, bone and brain. Studies were carried out using the murine ctcgrp null mouse model, which is completely void of calcitonin from conception onwards. Ctcgrp nulls were compared to the normal, wild-type (WT) siblings as controls. -- We have demonstrated that although calcitonin is unnecessary during pregnancy and the post-weaning period, it is indeed required physiologically during lactation since in its absence over half (51. 6% ± 4.6%) of the vertebral bone mineral content (BMC) is lost versus that seen in the WT (24.4% ± 5.4%). BMC losses were also significant within the hindlimb region and at the total body level. Loss of calcitonin during lactation is associated with increased trabecular thinning and separation. Despite these significant architectural changes, however, bone strength is no different in the ctcgrp null versus WT, likely due to a higher baseline bone volume in the ctcgrp null. -- Mechanisms underlying significant BMC losses in the ctcgrp null versus the WT include increased mammary production of PTHrP, increased circulating PTH and increased bone resorption. Pituitary contributions to bone loss appear to be less significant. Excess calcium lost during lactation does not occur as a result of compromised intestinal absorption or increased urinary excretion but is most likely lost in the milk supply. -- Our studies therefore confirm an important physiological role of calcitonin in protecting the maternal skeleton against excessive resorption during lactation. Important physiological pathways regulating bone resorption at this time include the breast and bone, with potential contributions coming from the brain. Furthermore, the post-weaning ctcgrp null skeleton may offer an ideal context in which skeletal recovery could be examined because anabolic mechanisms are likely upregulated.
TypeText
Resource TypeElectronic thesis or dissertation
FormatImage/jpeg; Application/pdf
SourcePaper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries
Local Identifiera3241924
RightsThe 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.
CollectionElectronic Theses and Dissertations
Scanning StatusCompleted
PDF File(28.49 MB) -- http://collections.mun.ca/PDFs/theses/Woodrow_JanineP.pdf
CONTENTdm file name34180.cpd