Growth hormone (GH) regulation of gastric structure and function in the GH-deficient rat: up-regulation of intrinsic factor.

Abstract

In a recent study we identified GH receptor/binding protein in cells of the gastric mucosa. In order to define the role of the GH receptor/binding protein in gastric function, we have investigated the effect of GH on gastric structure and function in the GH-deficient Lewis (dwarf) rat. Bovine GH, 65 micrograms/100 g body wt, was administered twice daily to adult male dwarf rats for 6 days (DW+) while control animals received vehicle only (DW-). Administration of GH produced a significant increase in body wt (P less than 0.001), stomach wt (P less than 0.01), and stomach to body wt ratio (P less than 0.05). GH administration also resulted in increased total gastric DNA, RNA, and protein content but did not produce significant differences in DNA, RNA, or protein content when normalized to stomach wt. Morphometric analysis of the gastric mucosa revealed a significantly (P less than 0.05) increased gastric epithelial height and mucosal surface area along with an increase in the proportion of nuclei with multiple nucleoli (P less than 0.01). The number of gastric mucosal cells in S-phase was determined by immunohistochemical detection of nuclear 5'-bromo-2'-deoxyuridine (BrdU) incorporated during a 2 h pulse of BrdU. GH treatment resulted in a 74% increase (P less than 0.05) in the number of BrdU-labeled nuclei/mm2 mucosa relative to vehicle-injected control animals. A modification of Zimmerman's method for the differential staining of gastric mucosa was used to delineate cell type for morphometric analysis. This showed that the density of differentiated (parietal and chief) cell types was not significantly different between DW- and to DW+ animals. Soluble extracts of gastric mucosa were prepared for estimation of pepsinogen content and [57Co]cyanocobalamin (vitamin B12) binding. GH administration produced no significant change in pepsinogen content per mg protein and did not affect the relative levels of pepsinogen isoenzymes as determined by polyacrylamide gel electrophoresis. GH administration did however result in an 86% increase (P less than 0.01) in [57Co]cyanocobalamin binding per mg protein. The increase in binding was totally displaceable by 1 microgram/ml unlabeled cyanocobalamin but not by 1 microgram/ml cobinamide dicyanide indicating it was the result of increased intrinsic factor rather than R protein. Sephadex S-300 gel filtration of mucosal extracts revealed an elution profile for [57Co]cyanocobalamin identical to that of purified porcine intrinsic factor and different from that of human salivary R protein. In conclusion, we have demonstrated that GH stimulates proliferation and enlargement of the gastric mucosa without significant alteration in cellular composition.(ABSTRACT TRUNCATED AT 400 WORDS)