ONTOGENY OF GASTRIN AND CHOLECYSTOKININ IN THE COLON AND DUODENUM OF SHEEP

The different roles of gastrin and cholecystokinin in the fetus compar ed to the adult may be reflected in different distribution patterns. R e-expression of these fetal patterns is often seen in tumours of the a dult. Using region-specific antisera and chromatography, we have deter mined the ontogeny of amidated gastrin (G-amide), glycine extended gas trin (G-gly), and cholecystokinin (CCK) in various segments of the col on 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 d ay lamb, and adult sheep were examined. In the colon, higher concentra tions of G-amide (2.8 +/- 0.2 pmol/g) and CCK (11.7 +/- 1.6 pmol/g) we re measured in the fetus while G-gly (0.7 +/- 0.1 pmol/g) was higher i n 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 l amb rather than the fetus contained the highest concentrations of G-am ide, 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 r esults demonstrate two major developmentally regulated features. First ly as the colon matures, there is a gradual switch between the express ion of the gastrin and CCK genes and secondly, the processing to G-ami de is attenuated. These findings suggest that non-amidated gastrin sho uld be examined for a potential role as a growth factor in colorectal carcinogenesis.