The role of gastrin in the development of the gastrointestinal tract in fetal sheep.

Abstract

We have investigated the role of gastrin in the development of the gastrointestinal tract during the latter part of gestation in fetal sheep. We surgically removed the major source of gastrin, the gastric (abomasal) antrum, from five fetuses at 90 days of gestation. The remaining abomasum was anastomosed to the pylorus allowing unobstructed flow of luminal contents. Another five fetuses, subjected to sham-antrectomies at 90 days, served as controls. Further surgery was performed in all fetuses at 120 days for the placement of vascular catheters to permit measurement of plasma gastrin concentrations. The fetuses were infused with [3H]thymidine to study villus cell migration rates. At 135 days of gestation samples of gastric (abomasal) fundus, and proximal and distal small intestine, were processed for histology and morphometric analysis. The antrectomized fetuses had significantly lowered plasma gastrin concentrations (P less than 0.025) between 120 and 135 days. At 135 days, the mean body weight, crown-rump length, total gut weight and small intestinal weight and length were not significantly different between the two groups. Similarly, there were no significant differences between groups in the mean thicknesses of the gut wall, mucosa and muscularis externa, or in the mean villus height and crypt depth in the proximal or distal parts of the small intestine. Villus cell migration rate in the proximal and distal small intestine was not affected by antrectomy. No simple relationship could be demonstrated between any of these parameters and plasma gastrin concentration. In the antrectomized fetuses, the mean crypt density and crypt-to-villus ratio were significantly reduced in the proximal small intestine (P less than 0.05), while only the density of villi was reduced in the distal small intestine (P less than 0.05). In the antrectomized fetuses there were significant correlations between plasma gastrin and the fraction of fundic mucosa occupied by gland and pit (P less than 0.005), and between plasma gastrin concentration and villus density (P less than 0.01) and crypt-to-villus ratio (P less than 0.025) in the proximal small intestine. In the sham group these correlations were absent. We conclude that the removal of the gastric antrum in fetal sheep results in decreased plasma gastrin concentration, and that gastrin appears to have a regulatory or trophic role on the gut mucosa in these circumstances.(ABSTRACT TRUNCATED AT 400 WORDS)