THE IMPORTANCE OF THE CENTROACINAR REGION IN CERULEIN-INDUCED MOUSE PANCREATIC GROWTH

Early proliferation events within different exocrine pancreatic cell compartments were studied in mice with or without cerulein administration. A technique with H-3-thymidine labeling of DNA-synthesizing cells was used. Groups of five animals were given either cerulein (20-mu-g/kg/24 h) or saline subcutaneously twice daily. H-3-thymidine was given as a single injection, 300-mu-Ci intraperitoneally, on the 3rd and 8th day of cerulein or saline administration, and the fraction of labeled cells in each cell compartment (H-3-thymidine labeling index, TLI) was calculated on the basis of autoradiographic analyses of the tissue. In a second set of experiments the distribution of the tracer between cell compartments, when given on the 3rd day of cerulein (saline) administration, was followed over a 5-day period. The highest proliferative rate was observed in the centroacinar cell compartment (TLI, 6%), and newly formed cells were accumulated during the 5-day 'chase' period. During the same time the relative amount of labeled centroacinar cells increased and comprised 40% of all labeled exocrine cells. The relative size of the compartment did not increase, indicating increased cell turnover with loss of or possibly migration of centroacinar cells into other pancreatic cell compartments. Weak and no trophic effects of cerulein were seen on the acinar and ductal cell populations, respectively. In the control group labeled ductal cells were significantly reduced during the chase period. This was not observed in the cerulein group, indicating addition of labeled cells to this compartment from other sources. A significant non-cerulein-dependent relative increase and decrease of the ductal and acinar cell compartments, respectively, were observed during the chase period. The results show a strong proliferative response in the centroacinar cell population on administration of cerulein and indicates an increased cell turnover in this compartment in parallel with a non-cerulein-dependent increase of the relative amount of ductal cells in the mouse pancreatic gland.