Regulation of amylase and chymotrypsinogen expression by dexamethasone and caerulein in serum-free-cultured pancreatic acinar AR4-2J cells. Influence of glucose

Abstract

The direct effects of dexamethasone and caerulein on two pancreatic enzymes, amylase and chymotrypsin, were determined in AR4-2J cells cultured under serum-free conditions at two glucose concentrations (1.0 and 4.5 g/l). In the absence of any hormone, the higher glucose concentration resulted in a 1.6-1.8-fold increase in the basal levels of amylase and chymotrypsinogen. Dexamethasone (50 nM) increased the biosynthesis and mRNA levels of both enzymes at both glucose concentrations. However, dexamethasone had a more pronounced effect on amylase biosynthesis (5-fold induction) than on chymotrypsinogen biosynthesis (1.8-fold induction). The parallel increases in mRNA and protein indicated the existence of pre-translational regulation. This is in contrast with what was observed in serum-containing media, where a translational regulation of amylase biosynthesis took place, probably under the control of both glucose and some serum factors. By contrast, caerulein (10 nM) exerted a more specific action on chymotrypsinogen. The increases in chymotrypsinogen mRNA were 2.2- and 2.1-fold, and increases in chymotrypsin activity were 1.6- and 2.9-fold at 1.0 and 4.5 g of glucose/litre respectively. Thus the regulation by caerulein occurred mainly through the enhancement of chymotrypsinogen transcription and/or mRNA stabilization.