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In the ensuing years, scientists across the globe have sought to understand the mechanisms by which adrenal hormones and their synthetic analogues produce their complex and varied actions. Particular attention has focused on the glucocorticoids, partly because they have a vital place in the treatment of inflammatory and autoimmune disorders but also because dysregulation of the secretion and\/or activity of endogenous glucocorticoids 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. This review considers some of the key advances that have been made in our understanding of the physiology, pathology and pharmacology of the glucocorticoids. Emphasis is placed on the molecular mechanisms of glucocorticoid signalling and the complex mechanisms that regulate the access of steroids in the systemic circulation to their receptors in their various target cells and tissues. In addition, consideration is given to the irreversible \u2018organisational\u2019 actions of glucocorticoids in perinatal life and to the potential role of the steroids in the aetiology of disease.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2006) <jats:bold>147<\/jats:bold>, S258\u2013S268. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706456\">10.1038\/sj.bjp.0706456<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706456","type":"journal-article","created":{"date-parts":[[2006,1,10]],"date-time":"2006-01-10T10:50:21Z","timestamp":1136890221000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":177,"title":["Glucocorticoids: exemplars of multi\u2010tasking"],"prefix":"10.1111","volume":"147","author":[{"given":"Julia C","family":"Buckingham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.298.6673.564"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-139-5_Part_1-200309020-00012"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90201-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(89)90073-7"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.137.2.794"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.0630213"},{"key":"e_1_2_12_8_1","first-page":"331","volume-title":"The Physiology of Immunity","author":"BUCKINGHAM J.C.","year":"1996"},{"key":"e_1_2_12_9_1","first-page":"482","article-title":"Secretion of corticotrophin\u2010releasing hormone and arginine vasopressin by the neonatal rat hypothalamus in vitro: age\u2010dependent maturation of the responses to cytokines and modulation by glucocorticoids and lipocortin 1","volume":"10","author":"BUCKINGHAM J.C.","year":"1997","journal-title":"Dev. 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