Parathyroid hormone-related peptide (PTHrP) regulates fetal-placental calcium transport through a receptor distinct from the PTH/PTHrP receptor
Parathyroid hormone-related peptide (PTHrP) regulates fetal-placental calcium transport through a receptor distinct from the PTH/PTHrP receptor
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DOI：
10.1073/pnas.93.26.15233
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发表时间：
1996-12-24
影响因子：
11.1
通讯作者：
Kronenberg, HM
中科院分区：
文献类型：
--
作者：
Kovacs, CS;Lanske, B;Kronenberg, HM
为了确定 PTHrP 在胎儿钙代谢中的作用，测量了 PTHrP 基因缺失纯合子 (HOM) 小鼠的血钙。妊娠第 18.5 天，HOM PTHrP 消融胎儿的离子钙和母胎钙梯度与其同窝胎儿相比显着降低。为了评估胎盘对 PTHrP 效果的贡献，在妊娠第 17.5 天，通过心内注射将 Ca-45 和 Cr-51-EDTA（作为血液扩散标记）施用给怀孕的杂合母鼠。注射后 5 分钟，与同窝出生的胎儿相比，HOM PTHrP 消融胎儿的整个胎儿 Ca-45 积累显着减少。 在给母鼠施用 Ca-45 和 Cr-51 之前 1 小时，每窝仔鼠在子宫内注射 PTHrP、PTH 或稀释剂片段。 PTHrP-(1-86)和PTHrP-(67-86)显着增加了HOM PTHrP消融胎儿中相对Ca-45的积累，但PTHrP(1-34)、PTH-(1-84)和稀释剂没有影响。最后，在缺乏PTH/PTHrP受体基因的胎儿小鼠上进行了类似的研究，HOM PTH/PTHrP中的离子钙显着减少 然而，母体注射Ca-45和Cr-51后5分钟，这些胎儿中Ca-45的相对积累显着增加，得出的结论是PTHrP是胎儿血钙和胎盘钙转运的重要调节剂，此外，PTHrP对胎盘钙转运的生物活性是由不使用PTH/PTHrP受体的分子中区指定的。
To determine the role of PTHrP in fetal calcium metabolism, blood calcium was measured in mice homozygous (HOM) for deletion of the PTHrP gene. On day 18.5 of gestation, ionized calcium and the maternal-fetal calcium gradient were significantly reduced in HOM PTHrP-ablated fetuses compared with that of their littermates. To assess the placental contribution to the effect of PTHrP, Ca-45 and Cr-51-EDTA (as a blood diffusional marker) were administered by intracardiac injection to pregnant, heterozygous dams on day 17.5 of gestation, Five minutes after the injection, whole fetal Ca-45 accumulation was significantly decreased in HOM PTHrP-ablated fetuses compared with that of their littermates, Next, two fetuses from each litter were injected in utero with fragments of PTHrP, PTH, or diluent 1 h before administering Ca-45 and Cr-51 for the dam. PTHrP-(1-86) and PTHrP-(67-86) significantly increased relative Ca-45 accumulation in HOM PTHrP-ablated fetuses, but PTHrP(1-34), PTH-(1-84), and the diluent had no effect, Finally, similar studies were performed on fetal mice that lacked the PTH/PTHrP receptor gene, Ionized calcium was significantly reduced in HOM PTH/PTHrP receptor-ablated fetuses, However, 5 min after maternal injection of Ca-45 and Cr-51, relative accumulation of Ca-45 was significantly increased in these fetuses, It was concluded that PTHrP is an important regulator of fetal blood calcium and placental calcium transport, In addition, the bioactivity of PTHrP for placental calcium transport is specified by a mid-molecular region that does not use the PTH/PTHrP receptor.