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A Journal on Endocrine System Diseases

Indexed/Abstracted in: EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,118

Frequency: Quarterly

ISSN 0391-1977

Online ISSN 1827-1634


Minerva Endocrinologica 2007 September;32(3):141-59


Glucocorticoids and 11β-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic sindrome

Stimson R. H., Walker B. R.

Endocrinology Unit Centre for Cardiovascular Science Queen’s Medical Research Institute University of Edinburgh, Edinburgh, UK

Central obesity is associated with type 2 diabetes mellitus, hypertension and dyslipidaemia. This cluster of risk factors is known as the metabolic syndrome, and also occurs in people with primary glucocorticoid excess (Cushing’s syndrome). Exogenous glucocorticoid use also increases the risk of cardiovascular disease. Circulating glucocorticoid concentrations are tightly controlled by the hypothalamic-pituitary-adrenal axis, however tissue glucocorticoid levels are also enhanced by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Transgenic overexpression of 11β-HSD1 in either adipose tissue or the liver in mice causes components of the metabolic syndrome, while transgenic deletion of 11β-HSD1 prevents adverse metabolic complications of obesity. Although plasma glucocorticoid levels are not elevated in obesity, dysregulation of 11β-HSD1 is observed with decreased activity in the liver and increased activity in adipose tissue. 11β-HSD1 is highly regulated, and dietary composition may be a powerful determinant of activity. Polymorphisms in the 11β-HSD1 gene are also associated with components of the metabolic syndrome. Inhibition of this enzyme appears to be an attractive option to treat metabolic disease. Selective 11β-HSD1 inhibitors in rodents cause weight loss, improve insulin sensitivity and delay progression of cardiovascular disease. Trials in humans though will be the ultimate test to determine if inhibition of 11β-HSD1 offers a new tool in the treatment of metabolic disease.

language: English


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