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

Area of Science:

• Neuroendocrinology
• Stress Physiology
• Comparative Medicine

Background:

• Strain-specific differences in stress responsiveness are known, but the underlying hypothalamic-pituitary-adrenal (HPA) axis mechanisms remain unclear.
• Understanding these differences is crucial for characterizing stress hypo- and hyperactivity.

Purpose of the Study:

• To investigate the impact of restraint stress on HPA axis function and stress ulcer development across different rat strains.
• To elucidate the role of glucocorticoid feedback in mediating stress responses.

Main Methods:

• Adult male Wistar-Kyoto (WKY), Fisher 344 (F-344), and Wistar rats underwent sham adrenalectomy, adrenalectomy, or adrenalectomy with corticosterone replacement.
• Animals were subjected to 2-hour water-restraint stress, followed by assessment of stress ulcers, anterior pituitary adrenocorticotropic hormone (ACTH), proopiomelanocortin mRNA, thymus weight, and hypothalamic corticotropin-releasing factor mRNA.

Main Results:

• Intact WKY rats showed significantly higher ulcer incidence, ACTH, and proopiomelanocortin mRNA levels compared to F-344 and Wistar rats.
• Adrenalectomy in WKY rats increased ulcer incidence but had minimal effects on thymus weight, ACTH, or corticotropin-releasing factor mRNA, unlike in other strains.
• Corticosterone replacement in WKY rats failed to reverse or even exacerbated adrenalectomy effects, contrasting with its restorative effects in F-344 and Wistar rats.

Conclusions:

• WKY rats display exaggerated and prolonged peripheral responses to stress, regulated by glucocorticoids.
• These findings suggest a defect in glucocorticoid negative feedback on the HPA axis in WKY rats.
• This impaired feedback mechanism contributes to the heightened stress vulnerability observed in WKY rats.