Русский 
English Reimagining the interaction between stress-induced glucocorticoids and gastric ulceration: the importance of a methodological approach
Background
Activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is a main distinctive feature of stress reaction. One of stress-related pathology is a form of gastric ulceration, called “stress ulcer”. Hans Selye attracted an attention to relation between stress-induced glucocorticoids and gastric ulcer when he described adrenal hypertrophy and gastric ulceration as the symptoms of a triad of stress. For several decades it has been generally accepted that glucocorticoids produced during stress are ulcerogenic hormones.
Aims
As this widely accepted view about ulcerogenic role of glucocorticoids produced during stress contradicts their adaptive role, we further clarified the question. Our work hypothesis was that stress-produced glucocorticoids are gastroprotective.
Methods
To verify the hypothesis, the effects of deficiency of stress-produced glucocorticoids with subsequent corticosterone replacement as well as the effects of blockade of glucocorticoid receptors on stress-induced gastric ulceration were studied in rats. To inhibit corticosterone production during severe stress we used several various methodological approaches: elimination of the hypothalamic corticotropin-releasing factor (CRF)-producing neurons, inhibition of CRF synthesis in hypothalamus, blockade of CRF receptor type 1, ACTH immunoneutralization, inhibition of corticosterone synthesis. Various types of immobilization in combination with low temperature were used as ulcerogenic stress stimuli in preliminary fasting rats. The experiments were performed according to the Declaration of Helsinki.
Results
We found that a reduction in corticosterone release in response to ulcerogenic stress aggravates gastric erosion produced by this stress. Pre-treatment rats with of glucocorticoid receptor antagonist RU-38486 also resulted in significant aggravation of stress-caused gastric injury. Moreover, we demonstrated that in rats with inhibited stress-induced corticosterone rise normally non-ulcerogenic stimuli are transformed into ulcerogenic ones. Additionally, our findings argue for the contribution of glucocorticoids to protective influence of preconditioning mild stress against stress-induced gastric injury.
Conclusions
The results of our experimental studies prove the adaptive, gastroprotective, nature of glucocorticoids produced during acute stress-caused activation of the HPA axis.
Funding
The study was supported by grant of Russian Science Foundation (RSF) № 19-15-00430.