Kovacs C S, Lanske B, Hunzelman J L, Guo J, Karaplis A C, Kronenberg H M
Endocrine Unit, Massachusetts General Hospital, Boston 02114, USA.
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15233-8. doi: 10.1073/pnas.93.26.15233.
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, 45Ca and 51Cr-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 45Ca 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 45Ca and 51Cr to the dam. PTHrP-(1-86) and PTHrP-(67-86) significantly increased relative 45Ca 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 45Ca and 51Cr, relative accumulation of 45Ca 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.
为确定甲状旁腺激素相关蛋白（PTHrP）在胎儿钙代谢中的作用，对PTHrP基因缺失的纯合子（HOM）小鼠进行血钙测量。在妊娠第18.5天，与同窝小鼠相比，HOM PTHrP基因敲除胎儿的离子钙和母胎钙梯度显著降低。为评估胎盘对PTHrP作用的贡献，在妊娠第17.5天通过心内注射向怀孕的杂合子母鼠给予45Ca和51Cr - 乙二胺四乙酸（作为血液扩散标志物）。注射后5分钟，与同窝小鼠相比，HOM PTHrP基因敲除胎儿的全胎45Ca积累显著减少。接下来，在向母鼠给予45Ca和51Cr前1小时，对每窝中的两只胎儿进行子宫内注射PTHrP、甲状旁腺激素（PTH）片段或稀释剂。PTHrP - (1 - 86)和PTHrP - (67 - 86)显著增加了HOM PTHrP基因敲除胎儿的相对45Ca积累，但PTHrP - (1 - 34)、PTH - (1 - 84)和稀释剂没有作用。最后，对缺乏PTH/PTHrP受体基因的胎儿小鼠进行了类似研究。HOM PTH/PTHrP受体基因敲除胎儿的离子钙显著降低。然而，母鼠注射45Ca和51Cr后5分钟，这些胎儿的45Ca相对积累显著增加。得出的结论是，PTHrP是胎儿血钙和胎盘钙转运的重要调节因子。此外，PTHrP对胎盘钙转运的生物活性由一个不使用PTH/PTHrP受体的中分子区域决定。
