de Groot C J, ten Voorde G H, van Andel R E, te Kortschot A, Gaasbeek Janzen J W, Wilson R H, Moorman A F, Charles R, Lamers W H
Biochim Biophys Acta. 1987 Apr 29;908(3):231-40. doi: 10.1016/0167-4781(87)90103-5.
In glucocorticosteroid-treated diabetic rats, glutamine synthetase enzyme levels in the liver are decreased 3-fold, whereas carbamoylphosphate synthetase enzyme levels are increased 2.3-fold. In addition, immunohistochemistry shows that under these conditions the distribution of carbamoylphosphate synthetase is expanded over the entire liver acinus, whereas that of glutamine synthetase is reduced to very few cells bordering the central (terminal hepatic) veins. Using a newly isolated cDNA complementary to rat liver glutamine synthetase mRNA, we show that this regulation is primarily effected at a pretranslational level. (For data on carbamoylphosphate synthetase mRNA levels, see De Groot et al. (1986) Biochim. Biophys. Acta 866, 61-67). Furthermore, hybridization studies show stimulatory effects of both glucocorticosteroids and thyroid hormone on the glutamine synthetase mRNA level. Attempts to localize glutamine synthetase mRNA within the liver acinus by selective destruction of the pericentral zone failed because of generally low levels of liver mRNAs after CCl4 poisoning. In contrast to the situation after birth, significantly higher glutamine synthetase mRNA/enzyme activity ratios in fetal rat liver point to the presence of additional post-transcriptional control mechanisms before birth. These findings complement similar observations on carbamoylphosphate synthetase gene expression (De Groot et al. (1986) Biochim. Biophys. Acta 866, 61-67).
在接受糖皮质激素治疗的糖尿病大鼠中，肝脏中的谷氨酰胺合成酶水平降低了3倍，而氨甲酰磷酸合成酶水平升高了2.3倍。此外，免疫组织化学显示，在这些条件下，氨甲酰磷酸合成酶的分布扩展到整个肝腺泡，而谷氨酰胺合成酶的分布则减少到仅位于中央（终末肝）静脉周围的极少数细胞。利用新分离的与大鼠肝脏谷氨酰胺合成酶mRNA互补的cDNA，我们表明这种调节主要在翻译前水平起作用。（关于氨甲酰磷酸合成酶mRNA水平的数据，见De Groot等人（1986年）《生物化学与生物物理学报》866卷，61 - 67页）。此外，杂交研究表明糖皮质激素和甲状腺激素对谷氨酰胺合成酶mRNA水平均有刺激作用。由于四氯化碳中毒后肝脏mRNA水平普遍较低，通过选择性破坏肝腺泡中央区来定位谷氨酰胺合成酶mRNA的尝试失败了。与出生后的情况相反，胎鼠肝脏中谷氨酰胺合成酶mRNA/酶活性比值显著更高，这表明出生前存在额外的转录后控制机制。这些发现补充了关于氨甲酰磷酸合成酶基因表达的类似观察结果（De Groot等人（1986年）《生物化学与生物物理学报》866卷，61 - 67页）。
