Moshage H J, de Haard H J, Princen H M, Yap S H
Biochim Biophys Acta. 1985 Jan 29;824(1):27-33. doi: 10.1016/0167-4781(85)90025-9.
Corticosteroids are known to stimulate the synthesis of a number of liver-specific proteins. The reports regarding the effect of glucocorticoid on albumin synthesis in vivo and in vitro are controversial. In an attempt to determine the mechanism by which glucocorticoid exerts its influence on hepatic albumin synthesis and to find an explanation for the conflicting data, we have studied the effect of dexamethasone disodium phosphate on albumin synthesis and albumin messenger RNA as determined by the molecular hybridization technique in hepatocytes in rat in vivo and in suspension culture. In hepatocyte suspension culture, addition of 0.48 microM dexamethasone in medium at zero time led to a significant increase (20%) in incorporation of labeled precursor into albumin as compared to control experiments; this was accompanied by a maintainance of the initial level of full-length albumin mRNA for a 9 h period. In hepatocytes cultured without dexamethasone in the medium there was a progressive loss of albumin mRNA content. Despite this finding, dexamethasone was not able to increase the albumin mRNA content in hepatocyte to a level higher than the initial value. Moreover, administration of this hormone either intraperitoneally or intravenously into rats did not lead to enhanced cell-free albumin synthesis or to an increased level of albumin mRNA. These findings suggest that glucocorticoid does not play an essential role in the regulation of albumin synthesis in vivo. In vitro, however, glucocorticoid leads to a preservation of the initial level of albumin mRNA and thus plays a role in the control of spontaneous dedifferentiation of liver cells in culture.
已知皮质类固醇可刺激多种肝脏特异性蛋白质的合成。关于糖皮质激素在体内和体外对白蛋白合成影响的报道存在争议。为了确定糖皮质激素对肝脏白蛋白合成产生影响的机制，并为相互矛盾的数据找到解释，我们采用分子杂交技术，研究了磷酸地塞米松二钠对大鼠体内肝细胞及悬浮培养肝细胞中白蛋白合成和白蛋白信使核糖核酸（mRNA）的影响。在肝细胞悬浮培养中，在零时向培养基中添加0.48微摩尔的地塞米松，与对照实验相比，标记前体掺入白蛋白的量显著增加（20%）；同时，全长白蛋白mRNA的初始水平在9小时内保持稳定。在培养基中无地塞米松培养的肝细胞中，白蛋白mRNA含量逐渐减少。尽管有这一发现，但地塞米松并不能使肝细胞中白蛋白mRNA含量增加到高于初始值的水平。此外，将这种激素经腹腔或静脉注射给大鼠，并未导致无细胞白蛋白合成增强或白蛋白mRNA水平升高。这些发现表明，糖皮质激素在体内白蛋白合成的调节中并不起重要作用。然而，在体外，糖皮质激素可使白蛋白mRNA的初始水平得以维持，因此在控制培养肝细胞的自发去分化中发挥作用。
