Targeting the pre-receptor metabolism of cortisol as a novel therapy in obesity and diabetes

Laura Gathercole, Paul Stewart

Research output: Contribution to journalReview article

66 Citations (Scopus)


Due to its impact upon health and the economy, the mechanisms that contribute to the pathogenesis of obesity and the metabolic syndrome are under intense scrutiny. In addition to understanding the pathogenesis of disease it is important to design and trial novel therapies. Patients with cortisol excess. Cushing's syndrome, have a phenotype similar to that of the metabolic syndrome and as a result there is much interest the manipulation of glucocorticoid (GC) action as a therapeutic strategy. Intracellular GC levels are regulated by 11 beta-hydroxysteriod dehydrogenase (11 beta-HSD1) which converts inactive cortisone to cortisol, thereby increasing local GC action. There is an abundance of data implicating 11 beta-HSD1 in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome and 11 beta-HSD1 is an attractive therapeutic target. Selective 11 beta-HSD1 inhibitors, which do not act upon 11 beta-HSD2 (which inactivates cortisol to cortisone) are in development. So far studies have primarily been carried out in rodents, with results showing improvements in metabolic profile. Data are now beginning to emerge from human studies and the results are promising. (c) 2010 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalThe Journal of Steroid Biochemistry and Molecular Biology
Issue number1-3
Publication statusPublished - 1 Oct 2010


  • Obesity
  • 11 beta-Hydroxysteroid dehydrogenase
  • Glucocorticoids
  • Diabetes


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