title: Parathyroid hormone contributes to regulating milk calcium content and modulates neonatal bone formation cooperatively with calcium.
abstract: To determine whether PTH and calcium (Ca) interact in neonatal bone formation, female lactating mice either heterozygous (PTH(+/-)) or homozygous (PTH(-/-)) for targeted deletion of the pth gene were fed either a normal (1% Ca, 0.6% phosphate) or high-Ca diet (2% Ca and 0.4% phosphate). Dietary effects on milk Ca content and Ca-regulating hormones were determined in dams, and the effects of milk content were assessed on bone turnover in 3-wk-old pups. On the normal diet, milk Ca and 1,25-dihydroxyvitamin D(3) levels were lower, but milk PTH-related protein levels were higher in the PTH(-/-) dams compared with the PTH(+/-) dams. On the high-Ca diet, milk Ca levels were higher, but milk 1,25-dihydroxyvitamin D(3) and PTH-related protein levels were lower in both PTH(+/-) and PTH(-/-) dams. In pups fed by PTH(-/-) dams compared with pups fed by PTH(+/-) dams on normal diets, bone mineral density, trabecular bone volume relative to tissue volume, and the number of osteoblasts were reduced in both PTH(+/-) (32.5 +/- 1.2 vs. 39.6 +/- 1.5 mg/cm(2), P < 0.05; 23.3 +/- 1.6 vs. 29.2 +/- 2.8%, P < 0.01; and 94.2 +/- 8.2 vs. 123.5 +/- 3.5/mm(2), P < 0.01, respectively) and PTH(-/-) (20.4 +/- 0.9 vs. 27.0 +/- 1.2 mg/mm(2), P < 0.05; 16.8 +/- 1.9 vs. 19.3 +/- 2.1%, P < 0.05; and 48.6 +/- 7.9 vs. 90.5 +/- 8.6/mm(2), P < 0.01, respectively) pups but were lower in the PTH(-/-) pups compared with the PTH(+/-) pups. In contrast, in pups fed by either PTH(+/-) or PTH(-/-) dams on the high-Ca diet, bone mineral density, bone volume/tissue volume, and osteoblast numbers were significantly higher, in both PTH(+/-) (50.5 +/- 1.7 vs. 58.7 +/- 2.0 mg/mm(2), P < 0.05; 37.9 +/- 5.2 vs. 46.1 +/- 5.1, P < 0.05; and 120.5 +/- 9.2 vs. 159.3 +/- 14.7/mm(2), P < 0.01, respectively) and PTH(-/-) (33.0 +/- 1.2 vs. 47.5 +/- 2.2 mg/mm(2), P < 0.001; 23.8 +/- 3.1 vs. 35.9 +/- 2.0, P < 0.05; and 78.7 +/- 10.1 vs. 99.8 +/- 13.6/mm(2), P < 0.05, respectively), and were highest in the PTH(+/-) pups fed by the PTH(+/-) dams on the high-Ca diet. These results indicate that PTH can modulate Ca content of milk, and that PTH and Ca can each exert cooperative roles on osteoblastic bone formation in the neonate.
authors.affiliation: Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Guofan
authors.initials: G
authors.lastname: Cao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gu
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ren
authors.forename: Lei
authors.initials: L
authors.lastname: Shu
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Tao
authors.forename: Andrew
authors.initials: A
authors.lastname: Karaplis
authors.forename: David
authors.initials: D
authors.lastname: Goltzman
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D015519:Bone Density / Q000235:genetics; D002118:Calcium / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D002762:Cholecalciferol / Q000032:analysis / Q000378:metabolism; D004357:Drug Synergism; D004435:Eating / Q000235:genetics; D005260:Female; D006128:Growth / Q000235:genetics; D007774:Lactation / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics* / Q000502:physiology; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein / Q000032:analysis / Q000378:metabolism
chemical_list: D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D002762:Cholecalciferol; D002118:Calcium