Peptide amidating activity and gastrin processing in the developing sheep pancreas.

Gastrin is a regulator of both gastric acidity and gastrointestinal growth and is expressed transiently in the neonatal ovine and human pancreas. C-terminal amidation of glycine extended gastrin (G-gly) to gastrin amide (G-amide) by peptidylglycine alpha-amidating mono-oxygenase (PAM) is the final processing step. To investigate the relationship between PAM and gastrin synthesis in the developing pancreas, we measured PAM activity and the concentrations of gastrins in ovine pancreatic extracts from 95 days of gestation onwards. Pancreatic PAM activity was highest in the 95-day-old fetus (138 +/- 29 pmol/h/mg protein, mean +/- S.E.M.) and decreased to 9.5 +/- 3.7 pmol/h/mg protein in the adult. The circulating enzyme was also highest in the youngest fetus (1840 +/- 165 pmol/h/ml plasma) decreasing to approximately 50% in the 135-day-old fetus, with no further significant changes. The concentration of bioactive G-amide in the pancreas was 2.0 +/- 0.6 pmol/g at 95 days of gestation, 3.4 +/- 0.9 pmol/g at 135 days and decreased to 0.7 +/- 0.1 pmol/g in the adult. The precursor G-gly followed a similar pattern but its concentration was less than 10% of G-amide. These results show that: (a) there are high levels of PAM activity in the ovine fetal pancreas and in the fetal circulation, (b) PAM activity is apparently not rate-limiting in the bioactivation of pancreatic gastrin and (c) the dual expression of both PAM and gastrin in the fetal pancreas is similar to that observed in peptide-secreting tumours of the adult.