Time course and cellular site of mitotic activity in the exocrine pancreas of the rat during sustained hormone stimulation

Previous studies from our laboratory indicate that the adaptive response of the exocrine pancreas of the rat to prolonged stimulation with optimal doses of caerulein (0.25 microgram X kg-1 X h-1) follows a characteristic time course in which each step in the secretory pathway is activated. The immediate response is the depletion of zymogen-granule stores followed by coordinate and anticoordinate changes in individual rates of (pro-)enzyme synthesis after a lag period of 2 h. The sum of such changes leads to an increase in total rate of protein synthesis by 3 h which is combined with acceleration of intracellular transport packaging and granule discharge. In the present study the time course of DNA synthesis and the labeling index of five populations of pancreatic cells have been analyzed after caerulein stimulation for periods ranging from 6 to 72 h, using in vivo labeling with 1 mu Ci/g 3H-thymidine 1 h prior to sacrifice of the animals. DNA synthesis did not change during the initial 18 h in spite of persistent stimulation indicated by a 80% reduction on enzyme content. Following this lag period a sharp rise in DNA synthesis 20- to 25-fold above control levels was observed, which decreased by 48 h to reach control levels by 72 h. Increase in DNA synthesis was most pronounced in animals with lowest enzyme content in the pancreas. From the five cell populations studied by autoradiography interlobular duct cells and islet cells had no significant increase in labeling index at any time of stimulation.