Pancreatic kallikrein gene expression: effects of glucocorticoids in vivo and in vitro

We examined the role of glucocorticoids in the regulation of pancreatic glandular kallikrein gene expression in vivo and in vitro. Adult male rats were adrenalectomized (Adx). Corticosterone pellets were administered to maintain either physiologic (Adx 1+) or high physiologic (Adx 3+) plasma corticosterone levels. Pancreatic kallikrein mRNA levels were examined by Northern hybridization and quantitated by slot-blot hybridization. Adrenalectomy resulted in a 75% +/- 14% (n = 4) increase in kallikrein mRNA as compared with sham-operated controls. This increase was completely reversed by exogenous corticosterone replacement to normal physiologic concentrations. Replacement with high corticosterone levels (Adx 3+) resulted in a decrease of kallikrein mRNA levels to 53% +/- 4% (n = 4) of controls. A significant negative correlation was observed between individual kallikrein mRNA levels and plasma corticosterone (r = -0.81, n = 12). In vitro, using the rat pancreatic acinar cell line AR42J, dexamethasone decreased kallikrein mRNA steady-state levels in a time- and dose-dependent manner. These data, therefore, indicate that physiologic concentrations of plasma corticosterone decrease pancreatic kallikrein mRNA levels in vivo, and that this is a direct effect on pancreatic acinar cells.