Growth of Pancreas and Gastrointestinal Mucosa in Antrectomized and Gastrin-Treated Rats*

Abstract

Growth responses to endogenous and exogenous gastrin were examined in the pancreas and gastrointestinal tract mucosa. Rats were either antrectomized to remove the primary source of endogenous gastrin or subjected to a sham operation. Three weeks after surgery, half of the antrectomized animals were injected ip with pentagastrin (250 microgram/day) four times per day. Injections were carried out for a week. Antrectomy resulted in serum gastrin levels approximately one third of normal. DNA synthesis and DNA and RNA content of the pancreas and oxyntic gland, duodenal, and colonic mucosa were significantly reduced by antrectomy. In each case, pentagastrin treatment restored DNA synthesis and RNA and DNA levels to normal. Significant decreases in pancreatic and colonic weights in antrectomized animals were also completely prevented by pentagastrin injection. These results indicate that endogenous gastrin has an important role in the regulation of pancreatic and colonic mucosal growth, in addition to its already established similar function in oxyntic gland mucosa.

Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones.

“…Similarly, gastrin has a potent trophic effect on the exocrine pancreas and the mucosa of the large and small bowel. Chronic administration of pentagastrin to antrectomized rats prevents the decrease in pancreatic and colonic weight (6,7).…”

“…The gastrointestinal hormones cholecystokinin (CCK) and secretin are the chief endocrine stimulants of pancreatic exocrine secretions (4). An important, recently established action of CCK, secretin, and gastrin is their ability to stimulate the growth of the exocrine pancreas (4)(5)(6)(7). The role that these gastrointestinal hormones play in the development and growth of pancreatic cancer is not clearly understood, but it is likely that they may influence the growth of malignant cells of the pancreas (8).…”

“…Inhibition of the growth of endocrine-dependent mammary, prostate, and pituitary tumors by analogs of hypothalamic hormones has recently been demonstrated (22)(23)(24) In the second experiment with hamsters bearing the ductal pancreatic adenocarcinoma ( (5)(6)(7). Although secretin is not as potent as CCK, it also increases pancreatic weight, DNA, RNA, and protein content (7).…”

Hormonal Control of Rat Fetal Pancreas Development

“…GRP and its antagonist D-Phe 6 -BN(6-13)-OMe (a gift from Dr. Thomas MacDonald Laboratory) were infused at doses of 0.18 and 12 Ìg kg -1 h -1 , respectively [19]. Pentagastrin (Peninsula, Belmont, Calif., USA) was infused at a dose of 2.38 Ìg kg -1 h -1 [20]. Hydrocortisone (a gift from Upjohn, Kalamazoo, Mich., USA) was infused at 417 or 833 Ìg kg -1 h -1 [11,21], and L-365,260, the CCK B receptor antagonist (a gift from Merck Sharp & Dohme, Westpoint, Pa., USA), was infused at 120 Ìg kg -1 h -1 , a dose 75% less than the 0.5 mg kg -1 h -1 of L-364,718 infused in the adult rat which inhibited pancreas growth induced by pancreatic juice diversion [22].…”

Changes in Rat Pancreas following Gastric Surgery Are Not Correlated with Basal Levels of Serum Gastrin or Plasma Cholecystokinin

“…Whether the ensuing trophic effects on the pancreas are correlated with changed basal levels of gastrin or cholecys tokinin (CCK) is a matter of debate. The serum gastrin level decreases after removal of the gastrin-producing part of the stomach, antrectomy, which also was found to induce pancreatic atrophy in the rat which was reversed after administration of gastrin or pentagastrin [1,2]. Although others could not verify that changes of the mea sured concentrations of serum gastrin after gastric surgery in the rat are correlated with changes in the pancreas [3], it has been claimed that gastrin exerts trophic effects in the pancreas [4,5], Neither exogenous nor endogenous hypergastrinemia has been shown to change the pancreat ic weight in the rat [6,7].…”