ENDOCRINE CONTROL OF STRESS-INDUCED HEAT-SHOCK PROTEIN-70 EXPRESSION IN-VIVO

Background. Stress adaptation requires interactions between the hypoth alamic-pituitary-adrenal axis, the sympathetic nervous system, and a f amily of intracellular stress response proteins termed heat shock prot eins (HSPs). These HSPs are present in every living organism and are s electively induced in the adrenal cortex and vascular smooth muscle af ter either surgical or restraint stress.Methods. We perturbed the hypo thalamic-pituitary-adrenal axis by implanting in the rat subcutaneous pellets containing either placebo or dexamethasone (25 mg), ovine cort icotropin releasing factor (CRF, 0.5 mg), or the glucocorticoid antago nist RU486 (5 mg) for 2 weeks before randomization to either 90 minute s of restraint stress or immediate sacrifice. The adrenal glands were weighted, trunk blood was collected for adrenocorticotropic hormone (A CTH) and corticosterone measurements, and RNA isolated from the adrena l glands and aorta was assayed for HSP70 messenger RNA expression by N orthern analysis. Results. Dexamethasone resulted in a twofold decreas e in adrenal weight (p < 0.05). ACTH and corticosterone levels were ma rkedly reduced in the dexamethasone treated group in the absence or pr esence of restraint stress. Restraint resulted in greater than 20-fold induction of HSP70 in both the adrenal gland and aorta of the placebo group compared with nonstressed controls (p < 0.01). Long-term dexame thasone treatment reduced adrenal HSP70 expression fourfold after rest raint (p < 0.5) compared with placebo-treated controls. Conclusions. T hese data show dramatic induction of HSP70 messenger RNA expression in adrenal and aortic tissues after restraint stress. Differential organ specific HSP regulation is evidenced by the ability of the glucocorti coid dexamethasone to attenuate the adrenal but not the aortic respons e. The significant effect of RU486 on the aortic response suggests the possibility of vascular glucocorticoid-catecholamine interactions.