title: 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-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.
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Beth J
authors.initials: BJ
authors.lastname: Kirby
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.forename: Heather M
authors.initials: HM
authors.lastname: Martin
authors.forename: Kerri L
authors.initials: KL
authors.lastname: Buckle Favaro
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Karaplis
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Kovacs
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000097:blood / Q000494:pharmacology; D004032:Diet; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D000090265:Klotho Proteins; D007774:Lactation / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010281:Parathyroid Hormone / Q000172:deficiency / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014809:Vitamin D-Binding Protein / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D015415:Biomarkers; C000717428:Fgf23 protein, mouse; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D014809:Vitamin D-Binding Protein; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D013250:Steroid Hydroxylases; C585550:Cyp24a1 protein, mouse; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D005966:Glucuronidase; D000090265:Klotho Proteins; D002117:Calcitriol; D002118:Calcium
keywords: ANIMAL MODELS, RODENT; BONE MINERALIZATION; CALCITRIOL; FGF23; GROWTH AND DEVELOPMENT; KNOCKOUT; LACTATION; PREGNANCY; PTH/PTHRP