Role of calcitriol in regulating maternal bone and mineral metabolism during pregnancy, lactation, and post-weaning recovery

Gillies, Brittany (2017) Role of calcitriol in regulating maternal bone and mineral metabolism during pregnancy, lactation, and post-weaning recovery. Masters thesis, Memorial University of Newfoundland.

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Abstract

Maternal physiology adapts throughout reproductive phases to meet the mineral needs of the fetuses and neonates. During pregnancy, intestinal calcium absorption doubles; conversely, during lactation, calcium is resorbed from the skeleton. Post-weaning, restoration of bone mineral content occurs, however the factors regulating these adaptations are unknown. Animals lacking the vitamin D receptor (VDR) or those deficient in vitamin D achieve post-weaning increases in bone mass, suggesting that calcitriol, the active form of vitamin D, is not required. An alternative explanation is that calcitriol may act through non-genomic receptors to have these effects. We used calcitriol-deficient Cyp27b1 null mice to test whether calcitriol is required for upregulation of intestinal calcium absorption and skeletal recovery post-weaning. Compared to WT, and despite a rescue diet containing 2 % calcium, at baseline Cyp27b1 nulls were hypocalcemic with markedly increased PTH and 30 % lower BMC; μCT displayed reduced femoral length, cortical thickness, and cortical area. During pregnancy serum calcium levels increased, PTH levels were reduced, and BMD increased by 45 %, so that all values became no different from WT. During lactation, serum calcium levels of Cyp27b1 nulls decreased, PTH levels increased, BMC declined more markedly than in WT, and bone strength decreased; μCT analysis confirmed extensive endocortical resorption. Post-weaning, serum calcium of Cyp27b1 null normalized, PTH levels remained high, BMC increased, and bone strength recovered; μCT confirmed recovery of cortical parameters. In comparison to WT mice, the Cyp27b1 null females display very low levels of calcitriol throughout pregnancy and lactation. Intestinal calcium absorption is upregulated in the Cyp27b1 null mice during pregnancy. In conclusion, calcitriolindependent mechanisms regulate mineral and bone metabolism during pregnancy and postweaning; however, absence of calcitriol leads to greater transient bone loss during lactation.

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