Pancreatic acinar cell amylase gene expression: Selective effects of adrenalectomy and corticosterone replacement

To examine the role of glucocorticoids in the regulation of the acinar pancreas, adult male rats were adrenalectomized (Adx) and replaced with no corticosterone (B), normal B, or high B. Plasma B concentration, body weight gain, and thymus weight were used as independent measures of treatment efficacy. Compared to controls, Adx animals had a 75 ± 0.5% (n = 30) reduction in pancreatic amylase content; a 50% decrease occurred within 1 day and the maximal 75% decrease was observed after 5 days. In Adx animals, amylase content was normalized by normal B replacement and was increased to 235 ± 39% (n = 30) of control by high B replacement. Furthermore, in all Adx rats, pancreatic content of amylase and plasma B concentration was significantly correlated (r = 0.81, n = 30). The effect of adrenalectomy was selective for amylase; contents of ribonuclease, chymotrypsin, and elastase were not altered. However, the effects of high B replacement were not selective, and increased the content of all digestive enzymes. To determine whether the changes in enzyme content were associated with changes in messenger RNA (mRNA), pancreatic RNA was probed with ³²P-labeled complementary DNAs for amylase, ribonuclease, and chymotrypsin. After adrenalectomy and B replacement there was a significant correlation only between amylase mRNA (r = 0.87, n = 13) and plasma B concentration. These data indicate that physiological levels of B have a selective effect on pancreatic amylase gene expression. In contrast, high levels of B have the separate, nonselective effect of increasing the content of all digestive enzymes without increasing corresponding mRNA levels.