Stress regulation of adrenocorticosteroid receptor gene transcription and mRNA expression in rat hippocampus: time-course analysis

Neuronal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) p roteins mediate the transcriptional effects of circulating glucocorticoids. These receptors bind the same DNA response element, yet mediate quite diff erent 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 thr hippo campal formation. Analysis of MR gene transcription using an intronic MR pr obe revealed a transient 50% decrease in MR hnRNA in CA1, CA3 and dentate g yrus at 60-120 min post-stress, consistent with glucocorticoid down-regulat ion 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 acut e stress, but GR mRNA was decreased 120 min post stress in all hippocampal subregions. Chronic stress exposure down-regulated CR mRNA in CA3 only; eff ects were first evident 7 days post stress and persisted for the entire str ess 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 tran sient decrease in MR hnRNA in the absence of mRNA changes suggests increase d MR mRNA stability. In contrast, acute stress decreases the availability o f GR mRNA without demonstrably affecting transcription, suggesting reduced GR mRNA stability. The results suggest that acute stress alters CR mRNA exp ression by largely post-transcriptional mechanisms. However, elevations in basal corticosterone secretion seen following chronic stress are not suffic ient to markedly down-regulate GR/MR expression in a long-term fashion. (C) 2000 Elsevier Science B.V. All rights reserved.