Fetal parathyroids are not required to maintain placental calcium transport.
We used Hoxa3 knockout mice and other mouse models to study the role of the fetal parathyroids in fetal calcium homeostasis. Hoxa3-null fetuses lack parathyroid glands, and absence of parathyroid hormone (PTH) was confirmed with a rodent PTH immunoradiometric assay. The ionized calcium level of Hoxa3-null fetuses was significantly lower than that of wild-type or heterozygous littermates or of the mother. Both the rate of placental calcium transfer and the plasma PTHrP level were normal in Hoxa3 mutants and their heterozygous siblings. Because we had previously observed an increase in placental calcium transfer in PTH/PTHrP receptor 1-null (Pthr1-null) fetuses, we assayed plasma PTHrP in those mice. Pthr1-null fetuses had plasma PTHrP levels 11-fold higher than those of their littermates. Northern analysis, immunohistochemical, and in situ hybridization studies of Pthr1-null fetuses indicated that liver and placenta had increased expression of PTHRP: In summary, loss of fetal parathyroids in Hoxa3-null fetuses caused marked hypocalcemia but did not alter placental calcium transfer or the circulating PTHrP level. The findings in the Pthr1-null fetuses indicate that several tissues may contribute to the circulating PTHrP level in fetal mice.
Kovacs
C S
CS
Faculty of Medicine-Endocrinology, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, Newfoundland A1B 3V6, Canada. ckovacs@mun.ca
Manley
N R
NR
Moseley
J M
JM
Martin
T J
TJ
Kronenberg
H M
HM
D000818:Animals; D001692:Biological Transport; D002116:Calcitonin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010280:Parathyroid Glands / Q000378:metabolism / Q000502:physiology*; D010281:Parathyroid Hormone / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D010920:Placenta / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
D018398:Homeodomain Proteins; C080331:Hoxa3 protein, mouse; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D002116:Calcitonin; D002118:Calcium