Stress regulation of adrenocorticosteroid receptor gene transcription and mRNA expression in rat hippocampus: time-course analysis.
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.
Paskitti
M E
ME
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, 800 Rose Street, 40536-0298, Lexington, KY, USA.
McCreary
B J
BJ
Herman
J P
JP
D000208:Acute Disease; D000375:Aging / Q000502:physiology; D000818:Animals; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000235:genetics / Q000503:physiopathology; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology*; D017403:In Situ Hybridization; D008137:Longitudinal Studies; D008297:Male; D012332:RNA, Heterogeneous Nuclear / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000235:genetics / Q000503:physiopathology*; D014158:Transcription, Genetic / Q000502:physiology*
D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid