Proliferative response of different exocrine pancreatic cell types to hormonal stimuli. I. Effects of long-term cerulein administration.

The trophic effect on the exocrine pancreas of the cholecystokinin analogue cerulein was studied in a long-term experiment (20 or 160 micrograms/kg/24 h for 14 days) in mice by measuring changes in pancreatic weight and protein, amylase, and DNA content. Further, the selective cell growth stimulation exerted by various doses of cerulein (4, 20, 54, 160 micrograms/kg/24 h) on different exocrine pancreatic cell types was studied by continuous administration of 3H-thymidine. In the first experiment animals given 20 micrograms/kg/24 h of cerulein had increased pancreatic weight and amylase and protein content, whereas the animals given the higher dose had unchanged weight and a less pronounced increase in amylase and protein content. The pancreatic DNA content was unaffected in the 20-micrograms group but was clearly decreased by the higher dose. In the second experiment a statistically significant increase over controls was found in the fraction of labeled ductal cells when 20, 54, and 160 micrograms of cerulein was administered. However, in the acinar cell population an increase was measured only in the 160-micrograms group. A tendency to nadir in cell labeling was observed in both acinar and ductal cell groups at less stimulation. Labeling of centroacinar cells increased in all cerulein-treated groups. The results show that all cell types of the exocrine pancreas can be forced into proliferation by the cholecystokinin analogue used and that there is preferential cell growth stimulation in the ductal and centroacinar cell populations.