Foetal Metabolism, Placental Transfer And Origin Of Gastrin Releasing Peptide In The Sheep

1. Plasma gastrin releasing peptide (GRP) is elevated in the foetal and maternal circulations of pregnant sheep. To determine the mechanisms for this increase the synthesis, secretion rate, metabolism and placental transfer of GRP were measured.2. Foetal metabolic clearance rate of GRP was significantly increased (P<0.05) compared to the non-pregnant ewe (19.9 +/- 2.6 (s.e.m.) and 11.8 +/- 2.0 mL/min per kg, respectively), Production rate of GRP in the foetus was four-fold higher than in the non-pregnant ewe reflecting the combination of the increased basal concentration and metabolic clearance rate in the foetus.3. Infused GRP did not cross the placenta, However, endogenous GRP was higher in the umbilical vein than in the umbilical artery, suggesting a uteroplacental origin for some of the GRP in the foetal circulation.4. Gastrin releasing peptide mRNA was synthesized in the pregnant endometrium with lower amounts found in the pregnant myometrium. No GRP mRNA was detected in the amnion or chorioallantois.5. The results show that the previously reported increase in foetal concentration of GRP is from foetal and uteroplacental sources and is not a result of immaturity of clearance mechanisms but rather from an increased production of GRP, With the demonstration that the uteroplacental unit synthesizes and stores GRP, additional studies on the regulation of GRP production from these sources are warranted.