HORMONAL CONTROL OF α2u GLOBULIN SYNTHESIS AND ITS mRNA IN ISOLATED HEPATOCYTES
HORMONAL CONTROL OF α2u GLOBULIN SYNTHESIS AND ITS mRNA IN ISOLATED HEPATOCYTES
复制标题
分离肝细胞中 α2u 球蛋白合成及其 mRNA 的激素控制
DOI：
10.1111/j.1749-6632.1980.tb29512.x
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发表时间：
1980
影响因子：
5.2
通讯作者：
P. Feigelson
中科院分区：
文献类型：
--
作者：
Ching;P. Feigelson
最初，μ球蛋白存在于雄性大鼠的尿液中，而雌性大鼠的尿液中不存在。肝摘除和免疫荧光研究均表明，占肝脏蛋白质合成的约 1% 的 azu 球蛋白在雄性大鼠肝脏的实质细胞中合成，分泌到血清中并在体内排泄。azu 球蛋白在体内的肝脏合成受到多种激素的控制：雄激素、甲状腺激素、垂体生长激素和糖皮质激素刺激 azu 球蛋白。无细胞系统或通过与 1x2" 球蛋白 cDNA 探针杂交，5 我们已经证明，体内糖皮质激素、6 甲状腺激素^,^ 和性激素！通过调节编码阿祖球蛋白的肝脏 mRNA 水平来调节该蛋白质的合成，而垂体生长激素在翻译上控制该蛋白质的合成。~这种多激素控制使单个激素对使用体内研究很难确定哪些激素直接作用于肝脏，哪些激素实际上调节其他激素的水平，从而间接影响肝球蛋白的生物合成。体外激素反应性μ球蛋白合成系统将提供直接信息，并有助于探索潜在的生化事件。因此，我们最近开发了一种分离的大鼠肝细胞悬浮系统来研究激素。这种制备方法使我们能够检查完整肝细胞的代谢，不受整个动物中发现的其他循环激素和代谢物的影响。多个实验室已证明，大鼠肝细胞悬浮液中的酪氨酸转氨酶和色氨酸加氧酶的肝活性受到糖皮质激素的调节。皮质醇也可以特异性刺激肝细胞中的纤维蛋白原合成。”还检查了肝细胞中尿素、I3 葡萄糖、14 脂肪酸合成酶和乙酰辅酶A羧化酶合成的激素调节。在我们的实验室中，我们已经证明酪氨酸转氨酶活性的诱导及其在肝细胞中的生物合成需要地塞米松和胰高血糖素或N6,O2-二丁酰CAMP的存在。在本报告中，我们展示了 az 的体外糖皮质激素诱导、球蛋白合成及其在大鼠肝细胞悬液中的 mRNA 水平、该蛋白的翻译后修饰和分泌以及地塞米松诱导该特定 mRNA 的可能机制。
Originally, mu globulin was found in the urine of male rats and absent from the urine of female rats.' Both liver extirpation and immunofluorescent studies have shown that azu globulin, which represents approximately 1% of hepatic protein synthesis, is synthesized in the parenchymal cells of male rat liver, secreted into the serum and excreted in the The hepatic synthesis of azu globulin in vivo is under multiple hormonal control: androgens, thyroid hormones, pituitary growth hormone, and glucocorticoids stimulate azu globulin As measured by translation in a wheat germ cell-free system or by hybridization to a 1x2" globulin cDNA probe,5 we have shown that the in vivo regulation of the synthesis of this protein by glucocorticoids,6 thyroid hormone^,^ and sex hormones! occurs via modulation of the level of the hepatic mRNA coding for azu globulin, whereas pituitary growth hormone controls the synthesis of this protein tran~lationally.~ This multihormonal control complicates investigation of the role of the individual hormones on the regulation of this specific mRNA in vivo. It is difficult, using in vivo studies, to ascertain which hormones act directly on the liver, and which hormones are actually modulating the level of other hormones and thus indirectly affecting the biosynthesis of hepatic ap, globulin. An in vitro hormone-responsive mu globulin synthesizing system would provide direct information and would enable exploration of the underlying biochemical events. Therefore, we have recently developed an isolated rat hepatocyte suspension system to study the hormonal control of azu globulin synthesis under defined conditions in vitro. Such preparation allows us to examine the metabolism of intact liver cells that are free from the influence of other circulating hormones and metabolites found in whole animals. Hormonal regulation of hepatic protein synthesis or enzyme activities in isolated rat hepatocyte suspensions has been demonstrated in several laboratories. The hepatic activities of tyrosine aminotransferase" and tryptophan oxygenase" in rat liver cell suspensions have been shown to be regulated by glucocorticoids. Fibrinogen synthesis in hepatocytes can also be specifically stimulated by cortisol." The hormonal regulation of the synthesis of urea,I3 glucose,14 fatty acid ~ynthetase'~ and acetyl CoA carboxyla~e'~ in liver cells has also been examined. In our laboratory we have shown that induction of tyrosine aminotransferase activity and its biosynthesis in hepatocytes re uires the presence of both dexamethasone and glucagon or N6, 02-dibutyryl CAMP. In this report, we demonstrate the in vitro glucocorticoidal induction of az, globulin synthesis and its mRNA level in rat hepatocyte suspensions, the posttranslational modification and secretion of this protein and the possible mechanisms involved in the induction of this specific mRNA by dexamethasone.