Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone

ABSTRACT Pregnancy invokes a doubling of intestinal calcium absorption whereas lactation programs skeletal resorption to provide calcium to milk. Postweaning bone formation restores the skeleton's bone mineral content (BMC), but the factors that regulate this are not established. We used Pth‐nu...

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Bibliographic Details
Published in:Journal of bone and mineral research 2013-09, Vol.28 (9), p.1987-2000
Main Authors: Kirby, Beth J, Ma, Yue, Martin, Heather M, Buckle Favaro, Kerri L, Karaplis, Andrew C, Kovacs, Christopher S
Format: Article
Language:English
Subjects:
25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics
25-Hydroxyvitamin D3 1-alpha-Hydroxylase - metabolism
ANIMAL MODELS, RODENT
Animals
Biomarkers - metabolism
Bone and Bones - drug effects
Bone and Bones - metabolism
Bone Density - drug effects
BONE MINERALIZATION
Bone Remodeling - drug effects
CALCITRIOL
Calcitriol - metabolism
Calcium
Calcium - blood
Calcium - pharmacology
Diet
Female
FGF23
Fibroblast Growth Factors - genetics
Fibroblast Growth Factors - metabolism
Glucuronidase - genetics
Glucuronidase - metabolism
GROWTH AND DEVELOPMENT
Kidney - drug effects
Kidney - metabolism
KNOCKOUT
LACTATION
Lactation - blood
Lactation - drug effects
Lactation - metabolism
Mice
Parathyroid Hormone - deficiency
Parathyroid Hormone - metabolism
Placenta - drug effects
Placenta - metabolism
PREGNANCY
PTH/PTHRP
Reproduction - drug effects
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Steroid Hydroxylases - genetics
Steroid Hydroxylases - metabolism
Up-Regulation - drug effects
Up-Regulation - genetics
Vitamin D
Vitamin D-Binding Protein - metabolism
Vitamin D3 24-Hydroxylase
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Summary:ABSTRACT Pregnancy invokes a doubling of intestinal calcium absorption whereas lactation programs skeletal resorption to provide calcium to milk. Postweaning bone formation restores the skeleton's bone mineral content (BMC), but the factors that regulate this are not established. We used Pth‐null mice to test whether parathyroid hormone (PTH) is required for postweaning skeletal recovery. On a normal 1% calcium diet, wild‐type (WT) and Pth‐null mice each gained BMC during pregnancy, declined 15% to 18% below baseline during lactation, and restored the skeleton above baseline BMC within 14 days postweaning. A 2% calcium diet reduced the lactational decline in BMC without altering the gains achieved during pregnancy and postweaning. The hypocalcemia and hyperphosphatemia of Pth‐null mice normalized during lactation and serum calcium remained normal during postweaning. Osteocalcin and propeptide of type 1 collagen (P1NP) each rose significantly after lactation to similar values in WT and Pth‐null. Serum calcitriol increased fivefold during pregnancy in both genotypes whereas vitamin D binding protein levels were unchanged. Absence of PTH blocked a normal rise in fibroblast growth factor‐23 (FGF23) during pregnancy despite high calcitriol. A 30‐fold higher expression of Cyp27b1 in maternal kidneys versus placenta suggests that the pregnancy‐related increase in calcitriol comes from the kidneys. Conversely, substantial placental expression of Cyp24a1 may contribute significantly to the metabolism of calcitriol. In conclusion, PTH is not required to upregulate renal expression of Cyp27b1 during pregnancy or to stimulate recovery from loss of BMC caused by lactation. A calcium‐rich diet in rodents suppresses skeletal losses during lactation, unlike clinical trials that showed no effect of supplemental calcium on lactational decline in BMC.
ISSN:0884-0431
1523-4681
DOI:10.1002/jbmr.1925