FETAL METABOLISM, PLACENTAL-TRANSFER AND ORIGIN OF GASTRIN-RELEASING PEPTIDE IN THE SHEEP

1. Plasma gastrin releasing peptide (GRP) is elevated in the foetal an d maternal circulations of pregnant sheep. To determine the mechanisms for this increase the synthesis, secretion rate, metabolism and place ntal transfer of GRP were measured. 2. Foetal metabolic clearance rate of GRP was significantly increased (P<0.05) compared to the non-pregn ant ewe (19.9 +/- 2.6 (s.e.m.) and 11.8 +/- 2.0 mL/min per kg, respect ively), Production rate of GRP in the foetus was four-fold higher than in the non-pregnant ewe reflecting the combination of the increased b asal concentration and metabolic clearance rate in the foetus. 3. Infu sed GRP did not cross the placenta, However, endogenous GRP was higher in the umbilical vein than in the umbilical artery, suggesting a uter oplacental origin for some of the GRP in the foetal circulation. 4. Ga strin releasing peptide mRNA was synthesized in the pregnant endometri um with lower amounts found in the pregnant myometrium. No GRP mRNA wa s detected in the amnion or chorioallantois. 5. The results show that the previously reported increase in foetal concentration of GRP is fro m 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 fro m these sources are warranted.