Corticotropin-Releasing Factor May Protect the Gastric Mucosa in Stress through Involvement of Glucocorticoids

The hypothalamic-pituitary-adrenal (HPA) axis activation belongs to the main characteristics of the stress. Stress may contribute to the development and progression of gastrointestinal disorders. For several decades it was generally accepted that glucocorticoids released during stress-induced activation of the HPA axis contribute to ulcerogenic effect of stress. However, the results of our investigations do not support the traditional point of view and suggest that glucocorticoids released during acute activation of the HPA axis are naturally occurring gastroprotective factors. It is known that exogenous corticotropin-releasing factor (CRF) induces an increase in glucocorticoid production and may also protect the gastric mucosa against stress-induced injury. However, it remained unknown whether glucocorticoids released in response to CRF injection contribute to its gastroprotective effect. In our study, we investigated this question. Intraperitoneal administration of CRF at the dose 1.25 mu g/kg 30 min before onset of 3-hour cold-restraint stress rapidly and markedly increased plasma corticosterone level before the stress and significantly suppressed the occurrence of stress-induced gastric erosion in control rats. To estimate the role of glucocorticoids in CRF-induced gastroprotection, the effect of CRF on the stress-induced gastric erosion was studied after acute reduction of corticosterone release by metyrapone or after occupation of glucocorticoid receptors by the antagonist RU-38486. Metyrapone administration caused a fast inhibition of corticosterone response to CRF and prevented its protective effects on the gastric mucosa against the stress-induced erosion formation. The gastroprotective effect of CRF was also prevented by the pretreatment rats with glucocorticoid receptor antagonist RU-38486. The results obtained suggest that CRF may protect the gastric mucosa against stress-induced gastric injury through involvement of glucocorticoids. Copyright (C) 2012 S. Karger AG, Basel