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a Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK b Department of Biochemical Pharmacology, The William Harvey Research Institute, London EC1M 6BQ, UK c Department of Human Anatomy and Genetics, The University of Oxford, South Parks Road, Oxford OX1 3QX, UK
Key Words: annexin 1 • HPA axis • glucocorticoids • cytokines
Address for correspondence: Julia C. Buckingham, Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN. Voice: 44-208-383-8034; fax: 44-208-383-8032. e-mail: j.buckingham{at}imperial.ac.uk
Annexin 1 (ANXA1) was originally identified as a mediator of the anti-inflammatory actions of glucocorticoids (GCs) in the host defense system. Subsequent work confirmed and extended these findings and also showed that the protein fulfills a wider brief and serves as a signaling intermediate in a number of systems. ANXA1 thus contributes to the regulation of processes as diverse as cell migration, cell growth and differentiation, apoptosis, vesicle fusion, lipid metabolism, and cytokine expression. Here we consider the role of ANXA1 in the neuroendocrine system, particularly the hypothalamo-pituitary-adrenocortical (HPA) axis. Evidence is presented that ANXA1 plays a critical role in effecting the negative feedback effects of GCs on the release of corticotrophin (ACTH) and its hypothalamic-releasing hormones and that it is particularly pertinent to the early-onset actions of the steroids that are mediated via a nongenomic mechanism. The paracrine/juxtacrine mode of ANXA1 action is discussed in detail, with particular reference to the significance of the secondary processing of ANXA1, the processes that control the intracellular and transmembrane trafficking of the protein of the molecule and the mechanism of ANXA1 action on its target cells. In addition, the role of ANXA1 in the perinatal programming of the HPA axis is discussed.
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