Glucocorticoids are gastroprotective under physiologic conditions

Abstract

Stress may contribute to the development and progression of gastrointestinal disorders. Activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is one of the main characteristics of stress. For several decades it was generally accepted that glucocorticoids released during stress are ulcerogenic hormones. We designed some experimental studies in rats to clarify the validity of this widely held view. To achieve this goal, we examined the effect of glucocorticoid deficiency followed by corticosterone replacement or the glucocorticoid receptor antagonist, RU-38486, on stress-induced gastric erosion and the parameters of gastric function in rats. The data obtained shows that the reduction in the stress-induced corticosterone release, or its actions, aggravates stress-caused gastric erosion. It is suggested that an acute increase in corticosterone during stress protects the stomach against stress-induced injury. According to our results, various ulcerogenic stimuli, similar to stress, induce an increase in corticosterone that helps the gastric mucosa to resist against a harmful action of ulcerogenic stimuli. Glucocorticoids exhibit their gastroprotective effect by both maintaining local defensive factors and inhibiting pathogenic elements. Furthermore, the contribution of glucocorticoids to gastroprotection is tightly related to their contribution to general body homeostasis. Glucocorticoids provide gastroprotective actions in co-operation with prosta-glandins, nitric oxide and capsaicin-sensitive sensory neurons. The results obtained do not support the traditional paradigm and suggest that glucocorticoids released during acute activation of the HPA axis are naturally occurring gastroprotective factors. In this article, we review our recent publications on the role of glucocorticoids in gastroprotection.