GASTRIN AFFECTS ENZYME-ACTIVITY AND GENE-EXPRESSION IN THE AGING RAT PANCREAS

The structural and functional properties of the pancreas are known to be affected by a number of hormones, particularly those of the gastrin-CCK family, yet little is known about the responsiveness of the pancreas to gastrin-CCK peptides during the latter stages of life. The present investigation examined the changes in pancreatic growth, the activity, and the steady-state mRNA levels of some of the digestive enzymes during advancing age and after administration of gastrin. Groups of 3-, 6-, 12-, and 16-month-old male Fischer-344 rats were infused (osmotic minipump) with either gastrin G-17 (250 ng/kg/h) or saline (controls) for 14 days. In control pancreas, aging resulted in slight progressive reduction in pancreatic DNA, RNA, and protein concentrations. This decrease was markedly enhanced by gastrin treatment in 16-month-old rats. Pancreatic amylase and trypsin (TRP) activities in these animals were also slightly decreased with aging, whereas the steady-state mRNA levels of both enzymes were significantly higher in 16-month-old rats than in their 3-month-old counterparts. However, in 16-month-old rats, the steady-state mRNA levels of amylase and TRP were significantly reduced after gastrin administration, when compared with the corresponding controls. Chymotrypsin (CHY) activity in the pancreas remained essentially unchanged between 3- and 12-month-old rats, but in 16-month-old animals it was markedly decreased. CHY activity was further reduced by gastrin treatment only in the 16-month-old group. We conclude that a) both age-associated and gastrin induced changes in the activity of pancreatic enzymes are not accompanied by parallel alterations in the steady-state mRNA levels of these enzymes, and b) gastrin caused an antiproliferative effect on the rat pancreas with advancing age.