Dietary regulation of levels of active mRNA coding for amylase and serine protease zymogens in the rat pancreas.

The mechanism by which changes in diet mediate levels of exportable enzymes and proenzymes in pancreatic tissue were studied in rats. The relative levels of mRNA coding for pancreatic amylase, lipase, procarboxypeptidases A and B, and the family of serine protease zymogens have been determined by the ability of isolated RNA to direct the synthesis of these products in a high-fidelity micrococcal nuclease-treated reticulocyte-lysate translation system. Translation products synthesized in vitro correlated directly with products synthesized in vivo in pancreatic lobules. Dietary adaptation was observed when dietary carbohydrate was increased from 0 to 58% at the expense of protein (81-23%). The increase in dietary carbohydrate over this range resulted in a 2-fold increase in amylase synthesis in pancreatic lobules and a 1.8-fold increase in mRNA-directed synthesis of amylase in the translation system in vitro. Concomitant with the decrease in dietary protein, synthesis of serine protease zymogens in pancreatic lobules and in the system in vitro decreased by approximately 50%. Over this range of dietary manipulation, ratios of amylase to serine proteases showed a 3.6-fold change. When dietary carbohydrate was further increased to 81% and protein reduced to 0, non-adaptive changes were observed since there was a decrease in amylase synthesis under conditions both in vivo and in vitro. mRNAs coding for pancreatic lipase and procarboxypeptidases A and B were unaffected by the dietary changes. These findings indicate that nutritional regulation in the tissue levels of pancreatic enzymes and proenzymes is mediated by changes in the content of active cytoplasmic mRNAs.