Endocrine Abstracts

Exogenous corticotropin-releasing factor (CRF) induces an increase in glucocorticoid production and also may protect the gastric mucosa against stress-induced injury. However, it remained unknown whether glucocorticoids released in response to CRF injection contribute to the gastroprotective effect of CRF. In the present study we investigated whether exogenous CRF may protect the gastric mucosa against gastric injury through involvement of glucocorticoids and, consequently, through CRF receptor subtype 1. Gastric injury was induced by 3 h cold-restraint stress (at 10 °C) or indomethacin (35 mg/kg) in conscious rats as well as by 3.5 h gastric ischemia-reperfusion in anaesthetized animals. We compared the effects of CRF administration (1.25 and 2.5 μg/kg, i.p.) on the gastric erosion in rats with normal and deficient corticosterone production as well as in rats with normal and occupied glucocorticoid receptors (by RU-38486, 20 mg/kg). Glucocorticoid deficiency was created by metyrapone (30 mg/kg). The selective CRF receptor subtype 2 antagonist, astressin2-B, was also used. Administration of CRF markedly increased plasma corticosterone levels and significantly suppressed the occurrence of gastric erosion induced by each stimulus. Metyrapone injected shortly before CRF administration caused a fast inhibition of CRF-induced corticosterone response and attenuated the protective effect of CRF on the gastric mucosa against the stress- and indomethacin-induced erosion. The gastroprotective effect of CRF was also attenuated by the pretreatment rats with glucocorticoid receptor antagonist RU-38486 in stress and indomethacin ulcerogenic models. Metyrapone and RU-38486 did not influence the protective effect of CRF on the gastric mucosa against ischemia-reperfusion-induced lesion. At the same time the protective effect of CRF on the gastric mucosa against ischemia-reperfusion-induced lesion was prevented by astressin2-B. The results obtained suggest that exogenous CRF may protect the gastric mucosa through involvement of glucocorticoids and, consequently, through CRF receptor subtype 1 as well as through CRF receptor subtype 2. Supported by RFBR grants-10–04–00605.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however, funding details unavailable.