Glucocorticoids, Annexin 1 and the Neuroendocrine–Immune Interface
Endogenous gluococorticoids are essential for life and synthetic glucocorticoids have a vital place in the treatment of inflammatory and autoimmune disorders, despite many unwanted effects. Understanding the mechanisms of glucocorticoid action and control is therefore of major significance. Annexin 1 (ANXA1) was originally identified as a mediator of the anti-inflammatory actions of glucocorticoids in the host defense system but subsequent work has shown that the protein serves as a signalling intermediate in the regulation of many diverse processes. Our research programme has focussed on the role of ANXA1 in the neuroendocrine system, particularly the hypothalamo-pituitary-adrenocortical (HPA) axis. In the anterior pituitary ANXA1 is expressed abundantly in, and secreted from the folliculostellate cells. We have characterised a paracrine mode of ANXA1 action in the pituitary gland and our studies have lead to a greater understanding of the processes that control the transmembrane trafficking of the protein, the mechanism of ANXA1 action on its target cells via formyl peptide receptors (FPR) and gender differences in ANXA1 control. Characterisation of the molecular pathways of ANXA1 control may identify new targets for therapeutic intervention as dysregulation of HPA activity is increasingly implicated in a number of common disorders that pose a growing clinical burden, such as obesity, type II diabetes, the metabolic syndrome, hypertension and depression.