title: Parathyroid hormone regulates fetal-placental mineral homeostasis.
abstract: Parathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis and skeletal development is uncertain. We hypothesized that despite its low circulating levels during fetal life, PTH plays a critical role in regulating these processes. To address this, we examined two different genetic models of PTH deficiency. Pth null mice have enlarged parathyroids that are incapable of making PTH, whereas Gcm2 null mice lack parathyroids but have PTH that arises from the thymus. Pth nulls served as a model of complete absence of PTH, whereas Gcm2 nulls were a model of severe hypoparathyroidism. We determined that PTH contributes importantly to fetal mineral homeostasis because in its absence a fetal hypoparathyroid phenotype results with hypocalcemia, hypomagnesemia, hyperphosphatemia, low amniotic fluid mineral content, and reduced skeletal mineral content. We also determined that PTH is expressed in the placenta, regulates the placental expression of genes involved in calcium and other solute transfer, and may directly stimulate placental calcium transfer. Although parathyroid hormone-related protein (PTHrP) acts in concert with PTH to regulate fetal mineral homeostasis and placental calcium transfer, unlike PTH, it does not upregulate in response to fetal hypocalcemia.
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Simmonds
authors.forename: Gerard
authors.initials: G
authors.lastname: Karsenty
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Karaplis
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Kovacs
mesh_terms: D000818:Animals; D005260:Female; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D021041:Placental Circulation; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D010281:Parathyroid Hormone