Gastroprotective Role of Glucocorticoid Hormones

Abstract

Abstract. Gastric ulcer disease remains widespread; a stressful lifestyle and nonsteroidal antiinflammatory drugs (NSAIDs) make significant contributions to this pathological situation. The findings overviewed here support the idea that glucocorticoid hormones released in response to acute stress or NSAIDs act as gastroprotective substances and exert many of the same actions in the stomach as prostaglandins (PGs) and nitric oxide (NO) as well as capsaicin-sensitive afferent neurons. Glucocorticoids exert a gastroprotective effect by both maintaining local defensive factors (mucosal blood flow and mucus production) and inhibiting pathogenic elements (gastric motility and microvascular permeability). Furthermore, they exert gastroprotective actions in co-operation with PGs, NO, and the afferent neurons; and their compensatory action is observed when the protective mechanism provided by either of these factors is impaired. The gastroprotective action of glucocorticoids is also associated with maintenance of general body homeostasis, including blood glucose levels and systemic blood pressure. In conclusion, glucocorticoids released in response to acute stress or NSAIDs are naturally occurring protective factors that play an important role in maintenance of the gastric mucosal integrity. This led us to re-evaluate the traditional paradigm that glucocorticoid hormones produced during activation of the hypothalamic-pituitary-adrenocortical axis are ulcerogenic in the stomach.

Dual action of glucocorticoid hormones on the gastric mucosa: how the gastroprotective action can be transformed to the ulcerogenic one

“…We have also shown that well-known nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin and aspirin at ulcerogenic doses induce a rise in corticosterone, which helps the gastric mucosa to resist the harmful actions of these ulcerogenic agents (Filaretova et al, 2002a, b;2005). The findings support the idea that glucocorticoids released during acute activation of the HPA axis caused by various ulcerogenic stimuli act as a gastroprotective hormone (Filaretova et al, 2001(Filaretova et al, , 2007 but not ulcerogenic ones. It is assume that adaptive action of glucocorticoid hormones released in stress conditions may also be applied to the gastric mucosa.…”

“…Accordingly our results glucocorticoid hormones released during activation of HPA axis may contribute to gastroprotection by maintaining local gastric mucosal homeostasis (Filaretova et al, 2007). The hormones may contribute to local gastric mucosal homeostasis through maintaining of general body homeostasis, including glucose and temperature homeostasis as well as systemic blood pressure, which could be a fundamental of their beneficial action on various gastric targets and, finally, on gastric mucosal integrity .…”

Pathophysiology of Gastric Ulcer Development and Healing: Molecular Mechanisms and Novel Therapeutic Options

“…Consistently with this contention, glucocorticoid antagonists enhanced the severity of stress-induced erosions, further supporting a protective role of these hormones during stress (Filaretova et al, 2001). The mechanisms through which glucocorticoids exert their protective effects include the maintenance of glucose homeostasis, the increase in mucosal blood flow and mucus secretion, and the attenuation of both enhanced gastric motility and microvascular permeability (Filaretova et al, 2007).…”

Therapy for Unhealed Gastrocutaneous Fistulas in Rats as a Model for Analogous Healing of Persistent Skin Wounds and Persistent Gastric Ulcers: Stable Gastric Pentadecapeptide BPC 157, Atropine, Ranitidine, and Omeprazole

“…In particular, 6a-methylprednisolone suppressed spontaneous healing of open wounds [35]. On the other hand, despite common evidence that use of glucocorticoids increases the risk of complicated peptic ulcer disease [7], corticosteroids were also shown to prevent stress gastric lesions in experimental animals (for a review see, e.g., [23,36]). …”