Defense of adrenocorticosteroid receptor expression in rat hippocampus: Effects of stress and strain

Neuronal mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) p roteins are glucocorticoid-activated transcription factors that bind identi cal DNA response elements yet transduce distinct physiological/transcriptio nal actions. The present study assessed regulation of adrenocorticosteroid receptor RNA and protein following intermittent stress exposure, using Spra gue Dawley (S-D) and stress-hyperresponsive Fischer 344 (F344) rat strains. The F344 (but not S-D) strain showed enhanced acute stress responsivity an d enhanced corticosterone secretion following prolonged stress. F344 rats a lso showed reduced responsiveness to a novel stressor after prolonged stres s exposure, suggestive of enhanced glucocorticoid negative feedback. Upon p rolonged 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 u tilization. In contrast, beta 5' splice variant, full-length mRNA, and MR p rotein expression were not affected by stress in either strain, implying th at transcriptional changes do not affect overall mRNA or protein expression . GR protein was increased in pyramidal and granule cell somata/nuclei of F 344 rats despite lack of a change in mRNA expression. These data suggest th at prolonged stress elicits restricted changes in MR and GR expression in t he F344 strain only. Overall, stable expression of adrenocorticosteroid rec eptors is rigorously defended in hippocampal neurons, apparently through tr anscriptional and posttranscriptional mechanisms.