Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
J Bone Miner Res. 2010 Mar;25(3):594-605. doi: 10.1359/jbmr.090825.
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.
甲状旁腺激素 (PTH) 在调节成人钙和骨骼内稳态方面发挥着重要作用，但 PTH 是否对调节胎儿-胎盘矿物质内稳态和骨骼发育完全必需仍不确定。我们假设，尽管在胎儿期其循环水平较低，但 PTH 在调节这些过程中起着关键作用。为了解决这个问题，我们研究了两种不同的 PTH 缺乏症遗传模型。Pth 基因敲除小鼠的甲状旁腺增大，无法产生 PTH，而 Gcm2 基因敲除小鼠缺乏甲状旁腺，但有来自胸腺的 PTH。Pth 基因敲除小鼠作为 PTH 完全缺失的模型，而 Gcm2 基因敲除小鼠是严重甲状旁腺功能减退症的模型。我们确定 PTH 对胎儿矿物质内稳态有重要贡献，因为在缺乏 PTH 的情况下，会导致胎儿甲状旁腺功能减退表型，表现为低钙血症、低镁血症、高磷血症、羊水矿物质含量低和骨骼矿物质含量减少。我们还确定 PTH 在胎盘中有表达，调节与钙和其他溶质转运相关的基因在胎盘中的表达，并可能直接刺激胎盘钙转运。尽管甲状旁腺激素相关蛋白 (PTHrP) 与 PTH 协同作用以调节胎儿矿物质内稳态和胎盘钙转运，但与 PTH 不同的是，它不会响应胎儿低钙血症而上调。
