Wong N C, Oppenheimer J H
J Biol Chem. 1986 Aug 5;261(22):10387-93.
In contrast to the rapid response of mRNA-S14 which occurs within 20 min after L-triiodothyronine (T3) administration, the induction of other rat hepatic mRNA sequences exhibits a lag time of several hours. We have studied the induction of mRNA-S11 which codes for a protein of pI 6.1 and an Mr of 22,500 as a model of such a slowly responsive gene. In addition to T3, both glucocorticoids and growth hormone regulate the expression of this gene. For each of these stimuli, the response exhibits a lag time of approximately 6 h. Following this lag time, there is a linear increase in the level of mRNA-S11 induced by a single maximal dose of T3, dexamethasone, and growth hormone to levels of 15-, 6-, and 3-fold, respectively, in excess of the hypothyroid base-line levels. The similarity in the lag time and the differences in maximal responses effectively argues against the possibility that the effect of one hormone is mediated exclusively by a change in the secretion or metabolism of another. Support for a direct action of T3 and glucocorticoids on the hepatic cell comes from the observation that these hormones stimulate mRNA-S11 in rat hepatocytes under primary culture. The increases in in vitro nuclear transcription measured following T3 and dexamethasone administration were clearly insufficient to account for the observed increases in mRNA. Furthermore, the hormonal induction of mRNA-S11 was promptly abrogated by cycloheximide (10 mg/kg) injected 6 h after the administration of T3 or dexamethasone at the time of the expected mRNA increase. The post-transcriptional control of the mRNA-S11 and its sensitivity to cycloheximide are similar to previously documented responses of the rapidly induced mRNA-S14 and suggest for both sequences a requirement for ongoing synthesis of rapidly turning over proteins. We speculate that the lag time of response of a given gene to T3 or glucocorticoid may be an intrinsic characteristic of the gene and may represent a common set of molecular events involved in the activation of that gene by diverse stimuli.
与L-三碘甲状腺原氨酸（T3）给药后20分钟内mRNA-S14的快速反应不同，其他大鼠肝脏mRNA序列的诱导表现出数小时的延迟时间。我们研究了编码pI 6.1和Mr为22,500的蛋白质的mRNA-S11的诱导情况，以此作为这种缓慢反应基因的模型。除了T3外，糖皮质激素和生长激素都调节该基因的表达。对于这些刺激中的每一种，反应都表现出约6小时的延迟时间。在这段延迟时间之后，由单一最大剂量的T3、地塞米松和生长激素诱导的mRNA-S11水平分别线性增加至超过甲状腺功能减退基线水平的15倍、6倍和3倍。延迟时间的相似性以及最大反应的差异有效地排除了一种激素的作用完全由另一种激素的分泌或代谢变化介导的可能性。T3和糖皮质激素对肝细胞直接作用的证据来自于这样的观察结果：这些激素在原代培养的大鼠肝细胞中刺激mRNA-S11。给予T3和地塞米松后测量的体外核转录增加显然不足以解释观察到的mRNA增加。此外，在给予T3或地塞米松6小时后，在预期mRNA增加时注射环己酰亚胺（10mg/kg）可迅速消除mRNA-S11的激素诱导。mRNA-S11的转录后调控及其对环己酰亚胺的敏感性与先前记录的快速诱导的mRNA-S14的反应相似，这表明这两个序列都需要持续合成快速周转的蛋白质。我们推测，给定基因对T3或糖皮质激素反应的延迟时间可能是该基因的固有特征，可能代表了多种刺激激活该基因所涉及的一组共同分子事件。
