Effect of Single and Repeated Immobilization Stress on the Heat Shock Protein 70/90 System of the Rat: Glucocorticoid-Independent, Reversible Reduction of Hsp90 in the Liver and Spleen

Heat shock proteins (hsps) and glucocorticoids are produced in response to many common stressors. In addition, hsps interact physically with the intracellular glucocorticoid receptor (GR) and facilitate its activation by the hormone. To study the effect of stress on the hsp70/90 system and the potential association of the system with the hypothalamic-pituitary-adrenal (HPA) axis, we subjected 3 month-old male Harlan-Sprague Dawley rats to single or repeated (once daily for 6 consecutive days) immobilizations, and measured hsp70/90 steady-state levels in a panel of tissues, as well as circulating ACTH and corticosterone concentrations before, during and after immobilization. Single or repeated immobilizations had, as expected, a profound stimulatory effect on the HPA axis but did not influence the steady-state levels of hsp70/90 in any of the gross brain regions (pituitary, hypothalamus, hippocampus or brain cortex) or most peripheral tissues (thymus, adrenal glands, testes) examined. The hsp90 levels, however, were markedly and reversibly decreased in the liver and spleen both by single and repeated immobilizations. The potential inhibitory effect of glucocorticoids on liver and spleen hsp90 was investigated in bilaterally adrenalectomized rats treated with placebo or oral pharmacologic doses of corticosterone for 1 week. Neither adrenalectomy nor corticosterone treatment had an effect on the hsp70/90 system, suggesting that factors other than glucocorticoids mediate the effect of stress on hsp90 concentrations in the liver and spleen. We conclude that acute and chronic stress are associated with a reversible reduction of hsp90 in the liver and spleen, and this appears independent of glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)