Defense of adrenocorticosteroid receptor expression in rat hippocampus: effects of stress and strain.
Neuronal mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) proteins are glucocorticoid-activated transcription factors that bind identical DNA response elements yet transduce distinct physiological/transcriptional actions. The present study assessed regulation of adrenocorticosteroid receptor RNA and protein following intermittent stress exposure, using Sprague Dawley (S-D) and stress-hyperresponsive Fischer 344 (F344) rat strains. The F344 (but not S-D) strain showed enhanced acute stress responsivity and enhanced corticosterone secretion following prolonged stress. F344 rats also showed reduced responsiveness to a novel stressor after prolonged stress exposure, suggestive of enhanced glucocorticoid negative feed-back. Upon prolonged stress, F344 rats down-regulated MR hnRNA in CA1, CA3, and dentate gyrus. Transcriptional changes were accompanied by decreased expression of the alpha 5' messenger RNA (mRNA) form, consistent with altered promoter utilization. In contrast, alpha 5' splice variant, full-length mRNA, and MR protein expression were not affected by stress in either strain, implying that transcriptional changes do not affect overall mRNA or protein expression. GR protein was increased in pyramidal and granule cell somata/nuclei of F344 rats despite lack of a change in mRNA expression. These data suggest that prolonged stress elicits restricted changes in MR and GR expression in the F344 strain only. Overall, stable expression of adrenocorticosteroid receptors is rigorously defended in hippocampal neurons, apparently through transcriptional and posttranscriptional mechanisms.
Herman
J P
JP
Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington 40536-0084, USA. jpherm00@pop.uky.edu
Watson
S J
SJ
Spencer
R L
RL
D000818:Animals; D003345:Corticosterone / Q000097:blood; D015536:Down-Regulation / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344 / Q000378:metabolism; D017207:Rats, Sprague-Dawley / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013312:Stress, Physiological / Q000097:blood / Q000378:metabolism*
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003345:Corticosterone