Husson A, Renouf S, Fairand A, Buquet C, Benamar M, Vaillant R
Laboratoire d'Endocrinologie, Unité de Recherche Associée 650, Centre National de la Recherche Scientifique, Faculté des Sciences et Techniques, Mont-Saint-Aignan, France.
Eur J Biochem. 1990 Sep 24;192(3):677-81. doi: 10.1111/j.1432-1033.1990.tb19275.x.
Argininosuccinate lyase (ASL), the fourth enzyme of the urea cycle, belongs to a group of liver enzymes appearing in the late foetal period in the rat. Several hormones, including glucocorticosteroids and insulin have been implicated in the control of the development of this enzyme activity. In this study, the cloned cDNA was used to measure the relative abundance of ASL mRNA in the livers of rats at various stages of perinatal development and in cultured foetal hepatocytes during hormonal manipulations. The ASL mRNA was first detectable on day 15.5 of gestation and increased in amount concomitantly with the rise in the enzyme activity, suggesting that the appearance of enzyme activity reflects the turning on of specific gene transcription. When foetal hepatocytes were exposed to dexamethasone, an increase in ASL mRNA was detected, which was completely abolished by addition of actinomycin D, suggesting a transcriptional effect of the steroid. In contrast, administration of cortisol to foetuses in utero had no effect on the mRNA level, suggesting that the steroid action is inhibited in the intra-uterine environment. Insulin might be the inhibiting factor since it completely repressed the dexamethasone-induced accumulation of ASL mRNA in foetal hepatocytes. These data were confirmed in vivo by experiments using streptozotocin, which produces insulin-depleted foetuses and causes the accumulation of ASL mRNA. This regulation of ASL mRNA by glucocorticoids and insulin could account for the modulation of the enzyme activity observed in vivo and in vitro.
精氨琥珀酸裂解酶（ASL）是尿素循环的第四步酶，属于大鼠胎儿后期出现的一组肝脏酶。包括糖皮质激素和胰岛素在内的几种激素与这种酶活性的发育调控有关。在本研究中，克隆的cDNA被用于测量围产期发育各阶段大鼠肝脏以及激素处理期间培养的胎儿肝细胞中ASL mRNA的相对丰度。ASL mRNA在妊娠第15.5天首次可检测到，其数量随着酶活性的升高而增加，这表明酶活性的出现反映了特定基因转录的开启。当胎儿肝细胞暴露于地塞米松时，检测到ASL mRNA增加，而加入放线菌素D可完全消除这种增加，这表明该类固醇具有转录作用。相反，对子宫内的胎儿给予皮质醇对mRNA水平没有影响，这表明类固醇作用在子宫内环境中受到抑制。胰岛素可能是抑制因子，因为它完全抑制了地塞米松诱导的胎儿肝细胞中ASL mRNA的积累。使用链脲佐菌素进行的体内实验证实了这些数据，链脲佐菌素可产生胰岛素缺乏的胎儿并导致ASL mRNA的积累。糖皮质激素和胰岛素对ASL mRNA的这种调节可以解释在体内和体外观察到的酶活性调节。
