Paskitti M E, McCreary B J, Herman J P
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, 800 Rose Street, 40536-0298, Lexington, KY, USA.
Brain Res Mol Brain Res. 2000 Sep 15;80(2):142-52. doi: 10.1016/s0169-328x(00)00121-2.
Neuronal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) proteins mediate the transcriptional effects of circulating glucocorticoids. These receptors bind the same DNA response element, yet mediate quite different cellular functions. The present study tests the hypothesis that acute and chronic stress, which cause increases in glucocorticoids sufficient to bind the GR, will regulate expression of the GR and MR genes in the hippocampal formation. Analysis of MR gene transcription using an intronic MR probe revealed a transient 50% decrease in MR hnRNA in CA1, CA3 and dentate gyrus at 60-120 min post-stress, consistent with glucocorticoid down-regulation of the MR gene. However, no changes were seen in full-length MR mRNA at any post-stress time point. In contrast, GR hnRNA was not affected by acute stress, but GR mRNA was decreased 120 min post stress in all hippocampal subregions. Chronic stress exposure down-regulated GR mRNA in CA3 only; effects were first evident 7 days post stress and persisted for the entire stress time-course (28 days). There was no evidence for down-regulation of GR hnRNA or MR hnRNA/mRNA at any point in the chronic stress regimen. The transient decrease in MR hnRNA in the absence of mRNA changes suggests increased MR mRNA stability. In contrast, acute stress decreases the availability of GR mRNA without demonstrably affecting transcription, suggesting reduced GR mRNA stability. The results suggest that acute stress alters GR mRNA expression by largely post-transcriptional mechanisms. However, elevations in basal corticosterone secretion seen following chronic stress are not sufficient to markedly down-regulate GR/MR expression in a long-term fashion.
神经元糖皮质激素受体（GR）和盐皮质激素受体（MR）蛋白介导循环糖皮质激素的转录作用。这些受体结合相同的DNA反应元件，但介导截然不同的细胞功能。本研究检验了以下假设：急性和慢性应激会导致糖皮质激素水平升高至足以与GR结合，进而调节海马结构中GR和MR基因的表达。使用内含子MR探针分析MR基因转录发现，应激后60 - 1220分钟时，CA1、CA3和齿状回中的MR核不均一RNA（hnRNA）瞬时下降50%，这与糖皮质激素对MR基因的下调作用一致。然而，在应激后的任何时间点，全长MR信使核糖核酸（mRNA）均未出现变化。相比之下，GR hnRNA不受急性应激影响，但应激后120分钟时，所有海马亚区的GR mRNA均下降。慢性应激暴露仅下调了CA3区的GR mRNA；应激7天后效应开始显现，并在整个应激过程（28天）中持续存在。在慢性应激方案的任何时间点，均未发现GR hnRNA或MR hnRNA/mRNA下调的证据。MR hnRNA瞬时下降而mRNA无变化表明MR mRNA稳定性增加。相反，急性应激降低了GR mRNA的可利用性，但未明显影响转录，提示GR mRNA稳定性降低。结果表明，急性应激主要通过转录后机制改变GR mRNA表达。然而，慢性应激后基础皮质酮分泌的升高不足以长期显著下调GR/MR表达。
