TISSUE-SPECIFIC EXPRESSION OF HEAT-SHOCK PROTEIN-70 AND PROTEIN-90 - POTENTIAL IMPLICATION FOR DIFFERENTIAL SENSITIVITY OF TISSUES TO GLUCOCORTICOIDS

Heat shock proteins (hsps) and glucocorticoids are key elements of the organism's adaptive response to adverse physiological conditions. Glucocorticoids are pleiotropic hormones acting through receptor-mediated processes and eliciting tissue-specific biologic effects. The inactive form of the glucocorticoid receptor (GR) in the cytoplasm appears to be bound to hsps of the 90K family (hsp90 alpha and hsp90 beta). This interaction facilitates binding of glucocorticoid to its receptor, and depends on the relative amounts of the interacting components, GR and hsp90. To gain insight into the mechanisms of glucocorticoid regulation in a physiological context, the level of the hsp70/90 system in a panel of tissues, including testis, spleen, liver, thymus, pituitary, hypothalamus, hippocampus, brain cortex, pineal and adrenal, was examined by Western blotting. The hsp90 component showed greater variation (up to about forty-fold) relative to the less variable (up to about three-fold) hsp70 component of the system. The relative distribution of the hsp90 alpha and beta forms in the various tissues was also examined by a combination of Western and Northern blotting techniques. It was found that the alpha form predominated in the brain and the testis and the beta form predominated in the other peripheral organs. There was no relation between tissue hsp90 content and differential expression of either form. These findings suggest that tissue hsp90 content, an important physiological parameter of cellular homeostasis, may confer tissue specificity and sensitivity to glucocorticoids.