From the Hypothalamic Regulation of the Pituitary-Adrenocortical Axis to the Involvement of Glucocorticoids in the Gastroprotective Effect of the Corticotropin-Releasing Factor

The paraventricular nucleus (PVN) of the hypothalamus is recognized as the main source of corticotropin-releasing factor (CRF) in the pituitary portal system. CRF plays a key role in the stress response by activating the hypothalamic-pituitary-adrenocortical (HPA) axis through a cascade of events culminating in the release of glucocorticoid hormones into the blood. Several mechanisms are involved in the control of HPA axis activation, including its feedback inhibition regarded as an important regulatory mechanism of glucocorticoid hormone production. In addition to adaptive physiological responses, varied somatic and mental disorders can develop in response to stress, including acute gastric mucosal lesions, erosions and ulcers. Stress activates both ulcerogenic and protective mechanisms of the gastric mucosa. The review was conceived to demonstrate how an endocrinological approach to gastroenterological problems contributed to elucidating the role of the HPA axis in regulating the maintenance of gastric mucosal integrity and thus led to new insights. Our findings on the role of the hypothalamic PVN in HPA axis activation and feedback inhibition paved the way for experimental studies, which showed that HPA axis activation is a gastroprotective component of the stress response, while glucocorticoid hormones produced in response to stress act as gastroprotective, not ulcerogenic, factors, as has been commonly believed. These data allowed suggesting that glucocorticoid hormones may also be involved in the gastroprotective effect of CRF, and our further studies confirmed that exogenous CRF is able to protect the gastric mucosa from both stress- and indomethacin-induced damage due to the involvement of glucocorticoid hormones. Taken together, these data provide a convincing argument in favor of the gastroprotective role of HPA axis activation.