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  • Title: Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 as a promising therapeutic target.
    Author: Wamil M, Seckl JR.
    Journal: Drug Discov Today; 2007 Jul; 12(13-14):504-20. PubMed ID: 17631244.
    Abstract:
    Chronically elevated glucocorticoid levels cause obesity, diabetes, heart disease, mood disorders and memory impairments. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyses intracellular regeneration of active glucocorticoids (cortisol, corticosterone) from inert 11-keto forms in liver, adipose and brain, amplifying local action. Obese humans and rodents show increased 11beta-HSD1 in adipose tissue. Transgenic mice overexpressing 11beta-HSD1 selectively in adipose tissue faithfully recapitulate metabolic syndrome. Conversely, 11beta-HSD1 knockout mice have a 'cardioprotective' phenotype, whose effects are also seen with 11beta-HSD1 inhibitors in rodents. However, any major metabolic effects of 11beta-HSD1 inhibition in humans are, as yet, unreported. 11beta-HSD1 null mice also resist cognitive decline with ageing, and this is seen in humans with a prototypic inhibitor. Thus 11beta-HSD1 inhibition is an emerging pleiotropic therapeutic target.
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