Rosewicz S, Logsdon C D
Department of Physiology, University of Michigan Medical School, Ann Arbor.
Gastroenterology. 1989 Oct;97(4):1005-10. doi: 10.1016/0016-5085(89)91510-2.
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.
我们在体内和体外研究了糖皮质激素在胰腺腺激肽释放酶基因表达调控中的作用。成年雄性大鼠进行了肾上腺切除术（Adx）。给予皮质酮微丸以维持生理水平（Adx 1+）或高生理水平（Adx 3+）的血浆皮质酮水平。通过Northern杂交检测胰腺激肽释放酶mRNA水平，并通过狭缝印迹杂交进行定量。与假手术对照组相比，肾上腺切除术导致激肽释放酶mRNA增加75%±14%（n = 4）。外源性皮质酮替代至正常生理浓度可完全逆转这种增加。高皮质酮水平替代（Adx 3+）导致激肽释放酶mRNA水平降至对照组的53%±4%（n = 4）。在个体激肽释放酶mRNA水平与血浆皮质酮之间观察到显著的负相关（r = -0.81，n = 12）。在体外，使用大鼠胰腺腺泡细胞系AR42J，地塞米松以时间和剂量依赖的方式降低激肽释放酶mRNA的稳态水平。因此，这些数据表明，血浆皮质酮的生理浓度在体内可降低胰腺激肽释放酶mRNA水平，并且这是对胰腺腺泡细胞的直接作用。
