Ontogeny of gastrin and cholecystokinin in the colon and duodenum of sheep

Abstract

The different roles of gastrin and cholecystokinin in the fetus compared to the adult may be reflected in different distribution patterns. Re-expression of these fetal patterns is often seen in tumours of the adult. Using region-specific antisera and chromatography, we have determined the ontogeny of amidated gastrin (G-amide), glycine extended gastrin (G-gly), and cholecystokinin (CCK) in various segments of the colon and compared it to the developmental profile in the duodenum. Fetal sheep aged 80-90, 115-125 and 135-144 days (term is 145 days), 7-14 day lamb, and adult sheep were examined. In the colon, higher concentrations of G-amide (2.8 +/- 0.2 pmol/g) and CCK (11.7 +/- 1.6 pmol/g) were measured in the fetus while G-gly (0.7 +/- 0.1 pmol/g) was higher in the adult compared to other age groups. The calculated G-gly/G-amide ratio was 0.4 in the fetus and 1.4 in the adult while the CCK/G-amide ratios were 5 in the fetus and 13 in the adult. The duodenum of the lamb rather than the fetus contained the highest concentrations of G-amide, G-gly and CCK (40.3 +/- 9.7, 2.0 +/- 0.4, 109.0 +/- 14.3 pmol/g, respectively) and at concentrations exceeding that in the colon. The results demonstrate two major developmentally regulated features. Firstly as the colon matures, there is a gradual switch between the expression of the gastrin and CCK genes and secondly, the processing to G-amide is attenuated. These findings suggest that non-amidated gastrin should be examined for a potential role as a growth factor in colorectal carcinogenesis.