Strain differences in hypothalamic-pituitary-adrenal activity and stress ulcer

Strain differences in stress responsiveness have been previously described, but specific components of the hypothalamic-pituitary-adrenal (HPA) axis responsible for stress hypo- or hyperactivity have not yet been characterized. This study proposed to analyze the effect of restraint stress on different measures of HPA function and stress ulcer in stress-ulcer prone Wistar-Kyoto (WKY) and Fisher 344 (F-344) rats and in the ulcer-resistant Wistar strain. Adult male rats of these strains were sham adrenalectomized, adrenalectomized, and adrenalectomized-replaced with corticosterone pellet. Ten days after surgery, animals were subjected to the 2-h ulcerogenic water restraint stress and killed 2 h later. Intact WKY rats had dramatically more ulcers and higher anterior pituitary adrenocorticotropic hormone (ACTH) and proopiomelanocortin mRNA levels than the other two strains. In WKY rats, adrenalectomy increased ulcer incidence but did not affect thymus weight. ACTH content, or hypothalamic corticotropin-releasing factor mRNA levels, in contrast to the profound effects of adrenalectomy on these parameters in the other strains. Furthermore, corticosterone replacement was either without effect or enhanced the effect of adrenalectomy on these parameters in WKY rats, while it reversed the effects of adrenalectomy in the other strains. These data imply that WKY rats respond to stress with enhanced and prolonged changes in peripheral functions that are regulated by glucocorticoids, suggesting the presence of impaired efficacy of the glucocorticoid negative feedback on HPA function.