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)

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

“…In the developing rat (from fetal stage until weaning), the oxyntic mucosa would be under functional and trophic control of circulating gastrin and it was thought therefore that gastrin would play a role in the maturation and growth of the mucosa. This was particularly demonstrated after antrectomy in fetal sheep (Avila et al 1989) following parenteral nutrition or oral ingestion in the rat . But it was recently shown that gastrin affects neither the oxyntic mucosa nor the endocrine cells before weaning in rat stomach.…”

Prenatal maturation, the timing of birth and how it may be regulated in domestic animals

“…There are however other important factors in GI development, notably the passage of fluid through the lumen (Trahair, Harding, Bocking, Silver & Robinson, 1986). The presence of gastrin, secreted by the fetal antrum, may have a trophic effect on the maturation of small intestinal villi (Avila, Harding, Young & Robinson, 1989). In addition to morphological changes, the induction of a number of GI enzymes occurs just before birth; these include increases in G-6Pase as well as rises in pancreatic and intestinal digestive enzymes (Calvert, 'Malka & Menaid, 1979;Henning, 1985) and it seems likely that corticosteroids play a part in these changes.…”

Gut Regulatory Peptide Levels in Bovine Fetuses and Their Dams between the 3rd and 9th Months of Gestation

“…Taken together, these diverse observations suggest that fetal endocrine cells release their secretory products in a regulated manner, and that peptides are capable to interfere with functional targets. The hypothesis is substantiated by the alteration of the development of intestinal mucosa when circulating concentrations of gastrin are decreased by antrectomy in sheep [4]. In this context, the significant positive correlation that was observed here between fetal plasma gastrin concentration and the growth of pancreas and stomach suggests that the relatively high circulating levels of this peptide may be relevant for trophicity.…”

“…Oldham and Thompson [3] have stressed the lack of knowledge on the effects of these peptides in the fetus. However, decreased plasma gastrin induced by antrectomy results in a lower development of gut mucosa in fetal lamb, and it was found that somatostatin infusion depressed plasma gastrin and pancreatic polypeptide (PP) [4]. During the last month of fetal life, the increasing plasma peptide concentration probably contributes to the growth of the digestive tract as well as to the enzyme content of the gastric and intestinal mucosa, and that of pancreas.…”