PARATHYROID HORMONE-RELATED PEPTIDE (PTHRP) REGULATES FETAL-PLACENTALCALCIUM-TRANSPORT THROUGH A RECEPTOR DISTINCT FROM THE PTH PTHRP RECEPTOR/

To determine the role of PTHrP in fetal calcium metabolism, blood calc ium was measured in mice homozygous (HOM) for deletion of the PTHrP ge ne. On day 18.5 of gestation, ionized calcium and the maternal-fetal c alcium gradient were significantly reduced in HOM PTHrP-ablated fetuse s compared with that of their littermates. To assess the placental con tribution to the effect of PTHrP, Ca-45 and Cr-51-EDTA (as a blood dif fusional marker) were administered by intracardiac injection to pregna nt, 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 fragme nts 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 r elative Ca-45 accumulation in HOM PTHrP-ablated fetuses, but PTHrP(1-3 4), PTH-(1-84), and the diluent had no effect, Finally, similar studie s 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 t hese 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.