Extra-Adrenal Glucocorticoid Synthesis in Mucosal Tissues and Its Implication in Mucosal Immune Homeostasis and Tumor Development

Abstract

While glucocorticoids (GC) exert broad effects on metabolism, behavior and immunity, local production of even small amounts of GC, which may act in a paracrine or even autocrine manner, enable a specific site of the body to regulate their exposure to GC according to their specific needs. Mucosal tissues, for example, are at the borderline to the outside world, and are therefore in constant contact with either harmless foreign particles or potentially pathogenic microorganisms, which might provoke devastating inflammatory disorders due to chronic stimulation of the mucosal immune system. Increasing the local concentration of immunoregulatory GC by extra-adrenal de novo GC synthesis or local reactivation of inactive serum metabolites provides a protective mechanism to either restore homeostasis after clearance of infection or to regulate the critical balance between immunity and tolerance.