Stimulation of Pancreatic Growth by Secretin, Caerulein, and Pentagastrin*

Abstract

The primary hormonal regulators of pancreatic exocrine secretion are secretin and cholecystokinin. In addition, cholecystokinin is known to stimulate the growth of the exocrine pancreas. The current study examines whether secretin also alters pancreatic growth by itself and whether it influences the trophic response to caerulein, a structural and functional homolog of cholecystokinin. Rats were injected every 8 h for 7 days with either saline, secretin (50 U/kg), caerulein (320 ng/kg), or a combination of the above doses of secretin and caerulein. After sacrificing the animals, the pancreas was isolated, and the in vitro incorporation of [³H]thymidine into DNA was measured. The pancreas was weighed, and the pancreatic content of DNA and RNA were also determined. Secretin and caerulein administered alone both caused significant increases in DNA synthesis and the pancreatic concentrations of both RNA and DNA. The effects of the two hormones on total pancreatic RNA and DNA showed potentiation when combined. The combination of secretin and caerulein increased pancreatic weight significantly more than the sum of the effects of the agents given alone. In all three cases, the RNA and DNA ratios were significantly increased, indicating that hypertrophy as well as hyperplasia occurred. In a similar experiment, pentagastrin (250 μg/kg) also stimulated pancreatic growth. Secretin, when combined with pentagastrin, had no further effect or slightly reduced the trophic effects of pentagastrin. The effect of secretin on the pancreas contrasted dramatically with its effects on the oxyntic gland mucosa of the stomach. Secretin by itself had no trophic action on the stomach and completely inhibited the increase in DNA synthesis and DNA and RNA content stimulated by pentagastrin. In conclusion, secretin, like cholecystokinin and gastrin, produces both pancreatic hyperplasia and hypertrophy and may function in the regulation of the growth of this organ as well as its secretion. The most important aspect of the trophic action of secretin may be its ability to potentiate the effects of cholecystokinin. (Endocrinology106: 323, 1980)