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This Article Full Text Full Text (PDF) All Versions of this Article: 92/2/299    most recent expphysiol.2006.036194v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McMaster, A. Articles by Ray, D. W. Search for Related Content PubMed PubMed Citation Articles by McMaster, A. Articles by Ray, D. W. Related Collections Review Articles

¹ Endocrine Sciences Research Group, Room 3-903, Stopford Building, University of Manchester, Manchester M13 9PT, UK

Glucocorticoid hormones exert a wide spectrum of metabolic and immunological effects. They are synthesized from a cholesterol precursor and are structurally related to the other steroid hormones, progesterone, aldosterone and oestrogen. They act through the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. The GR is an intracellular receptor; the hydrophobic ligand accesses its receptor by diffusion across the plasma membrane. The ligand-activated GR translocates to the nucleus to regulate expression of its target genes. The GR, in common with the rest of the receptor family, can be functionally divided into an N-terminal transcription activation domain, a central DNA binding domain and a C-terminal ligand binding domain, which also includes a second transactivation domain. Although synthetic glucocorticoids are the most potent anti-inflammatory agents known, their use is limited owing to the range and severity of their side-effects. The structure of the ligand binding domain of the glucocorticoid receptor has now been solved, and a series of studies has shown that even subtle changes to the ligand structure alter the final conformation of the ligand–receptor complex, with consequences for further protein recruitment and for the function of the receptor. This, coupled with the successful development of selective oestrogen receptor agonists, has led to concerted efforts to find selective GR ligands, with preserved beneficial anti-inflammatory activity, but reduced side-effect profile. Current efforts have identified several useful tool compounds, and further molecules are in development in several pharmaceutical companies.

(Received 24 October 2006; accepted after revision 16 November 2006; first published online 30 November 2006)
Corresponding author D. W. Ray: Endocrine Sciences Research Group, Room 3-903, Stopford Building, University of Manchester, Manchester M13 9PT, UK. Email: david.w.ray{at}man.ac.uk

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				A McMaster, T Chambers, Q-J Meng, S Grundy, A S I Loudon, R Donn, and D W Ray Real-time analysis of gene regulation by glucocorticoid hormones J. Endocrinol., May 1, 2008; 197(2): 205 - 211. [Abstract] [Full Text] [PDF]