Rosewicz S, Logsdon C D
Department of Gastroenterology, Klinikum Steglitz, Freie Universität Berlin, Germany.
Gastroenterology. 1991 Oct;101(4):1102-8. doi: 10.1016/0016-5085(91)90740-c.
The effects of dexamethasone on ornithine decarboxylase gene expression were examined in rat pancreatic AR42J cells. Dexamethasone increased ornithine decarboxylase activity and messenger RNA (mRNA) concentrations in a time-dependent manner, with a maximal effect at 12 hours (207% +/- 63% and 327% +/- 34% of control, respectively; n = 5). Ornithine decarboxylase mRNA levels returned to control values at 48 hours, whereas ornithine decarboxylase activity was decreased to 41% +/- 8% of control (n = 3). Dexamethasone induction of ornithine decarboxylase mRNA was dose dependent, with half-maximal effects at 10(-8) mol/L (210% +/- 20% of control; n = 4) and maximal effects at 10(-7) mol/L (327% +/- 26% of control; n = 4). The glucocorticoid antagonist RU 38486 blocked the dexamethasone effects in a dose-dependent manner, with maximal effects occurring at 10(-7) mol/L (120% +/- 18% of control; n = 3). When protein synthesis was blocked by addition of cycloheximide, ornithine decarboxylase mRNA levels remained unchanged in response to glucocorticoids, indicating a primary effect of dexamethasone. Furthermore, cycloheximide by itself had no significant effect on ornithine decarboxylase mRNA levels. Inhibition of transcription with actinomycin D showed a half-life for ornithine decarboxylase mRNA of approximately 240 minutes. Ornithine decarboxylase mRNA stability was not affected by dexamethasone pretreatment for 12 hours. Therefore, these data suggest that dexamethasone regulates ODC gene expression via glucocorticoid receptor-mediated gene transcription. Furthermore, translational mechanisms seem to be involved in glucocorticoid-regulated ornithine decarboxylase induction.
在地鼠胰腺AR42J细胞中研究了地塞米松对鸟氨酸脱羧酶基因表达的影响。地塞米松以时间依赖性方式增加鸟氨酸脱羧酶活性和信使核糖核酸（mRNA）浓度，在12小时时达到最大效应（分别为对照的207%±63%和327%±34%；n = 5）。鸟氨酸脱羧酶mRNA水平在48小时时恢复到对照值，而鸟氨酸脱羧酶活性降至对照的41%±8%（n = 3）。地塞米松诱导鸟氨酸脱羧酶mRNA呈剂量依赖性，在10^(-8) mol/L时达到半数最大效应（为对照的210%±20%；n = 4），在10^(-7) mol/L时达到最大效应（为对照的327%±26%；n = 4）。糖皮质激素拮抗剂RU 38486以剂量依赖性方式阻断地塞米松的作用，在10^(-7) mol/L时达到最大效应（为对照的120%±18%；n = 3）。当通过添加环己酰亚胺阻断蛋白质合成时，鸟氨酸脱羧酶mRNA水平在糖皮质激素作用下保持不变，表明地塞米松的主要作用。此外，环己酰亚胺本身对鸟氨酸脱羧酶mRNA水平没有显著影响。用放线菌素D抑制转录显示鸟氨酸脱羧酶mRNA的半衰期约为240分钟。地塞米松预处理12小时不影响鸟氨酸脱羧酶mRNA的稳定性。因此，这些数据表明地塞米松通过糖皮质激素受体介导的基因转录调节ODC基因表达。此外，翻译机制似乎参与了糖皮质激素调节的鸟氨酸脱羧酶诱导。
