Iynedjian P B, Jacot M M
Eur J Biochem. 1980 Oct;111(1):89-98. doi: 10.1111/j.1432-1033.1980.tb06078.x.
The glucocorticoids induce the synthesis of phosphoenolpyruvate carboxykinase (GTP) in rat kidney as a consequence of an increase in the level of the specific enzyme mRNa. The mRNA induction was characterized with respect to its time course after hormone administration and its sensitivity to cycloheximide. The level of rat kidney mRNA directing the synthesis of phosphoenolpyruvate carboxykinase in wheat germ translation system nearly doubled within 2 h of a dexamethasone injection and further increased to four times the initial value at 6 h of treatment and to five times at 10 h. Cycloheximide injected 30 min prior to dexamethasone prevented the mRNA increase. When injected 5 h after dexamethasone, the inhibitor of protein synthesis blocked the rise of phosphoenolpyruvate carboxykinase mRNA occurring normally between 5 h and 10 h after treatment with dexamethasone. Maximal inhibitions of protein synthesis on the one hand and of mRNA induction on the other were achieved at the same dose of cycloheximine, suggesting that the two effect might be related. Dexamethasone caused an increase in the functional level of several as yet unidentified mRNAs in addition to that coding for phosphoenolpyruvate carboxykinase. The main points emerging from this study are: (a) the virtual absence of lag between dexamethasone administration and increase in phosphoenolpyruvate carboxykinase mRNa; (b) the inhibition of phosphoenolpyruvate carboxykinase mRNA induction by cycloheximide, suggesting a possible requirement for ongoing protein synthesis; (c) the existence in the kidney of a glucocorticoid-responsive domain comprising several distinct proteins.
糖皮质激素可诱导大鼠肾脏中磷酸烯醇丙酮酸羧激酶（GTP）的合成，这是由于特异性酶mRNA水平升高所致。对mRNA诱导作用的特征进行了研究，涉及激素给药后的时间进程及其对放线菌酮的敏感性。在小麦胚芽翻译系统中指导磷酸烯醇丙酮酸羧激酶合成的大鼠肾脏mRNA水平，在注射地塞米松后2小时内几乎增加了一倍，在治疗6小时时进一步增加到初始值的四倍，在10小时时增加到五倍。在注射地塞米松前30分钟注射放线菌酮可阻止mRNA增加。在注射地塞米松5小时后注射时，蛋白质合成抑制剂可阻断地塞米松治疗后5小时至10小时之间正常发生的磷酸烯醇丙酮酸羧激酶mRNA的升高。在相同剂量的放线菌酮下，一方面蛋白质合成受到最大抑制，另一方面mRNA诱导也受到最大抑制，这表明这两种效应可能相关。地塞米松除了导致编码磷酸烯醇丙酮酸羧激酶的mRNA增加外，还使几种尚未鉴定的mRNA的功能水平升高。本研究得出的主要观点如下：（a）地塞米松给药与磷酸烯醇丙酮酸羧激酶mRNA增加之间几乎没有延迟；（b）放线菌酮抑制磷酸烯醇丙酮酸羧激酶mRNA的诱导，提示可能需要持续的蛋白质合成；（c）肾脏中存在一个由几种不同蛋白质组成的糖皮质激素反应域。
