DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



In vivo activity of 11beta-hydroxysteroid dehydrogenase type 1 in man: effects of prednisolone and chenodesoxycholic acid.

Author(s): Diederich S, Quinkler M, Mai K, Schoneshofer M, Baehr V, Pfeiffer A, Oelkers W, Eigendorff E

Affiliation(s): Department of Endocrinology, Diabetes and Nutrition, Charite Campus Benjamin Franklin, Berlin, Germany. sven.diederich@endokrinologikum.com

Publication date & source: 2011-01, Horm Metab Res., 43(1):66-71. Epub 2010 Oct 5.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

The 11beta-hydroxysteroid dehydrogenases (11beta-HSDs) play a pivotal role in glucocorticoid (GC) action. 11beta-HSD1 is a predominant reductase, activating GCs from inert metabolites, whereas 11beta-HSD2 is a potent dehydrogenase inactivating GCs. Knowing the metabolic effects of GCs, a selective inhibition of 11beta-HSD1 represents a potential target for therapy of impaired glucose tolerance, insulin insensitivity and central obesity. In vitro, 11beta-HSD1 is selectively inhibited by chenodesoxycholic acid (CDCA) and upregulated under GC exposure. Therefore, we aimed to investigate the effects of CDCA and prednisolone on hepatic 11beta-HSD1 activity in vivo by measuring 11-reduction of orally given cortisone (E) acetate to cortisol (F). CDCA or placebo was given to 5 male healthy volunteers within a randomised cross-over trial before and after oral administration of 12.5 mg E acetate at 8:00 h. For measurement of in vivo effects of GCs on 11beta-HSD1 activity, hepatic reduction of 25 mg E acetate before and after treatment with prednisolone (30 mg for 6 days) was determined in 7 healthy males. Serum GC levels were determined using a fully automated liquid chromatographic system. CDCA had no effect on the activity of 11beta-HSD1 in vivo. Prednisolone therapy leads to a marked rise in serum F concentrations and an elevated F/E serum ratio. This proves GC-induced activation of hepatic 11beta-HSD1, which could not be extinguished by a parallel increase of IGF-1 under prednisolone. CDCA does not affect in vivo activity of 11beta-HSD1 when given in therapeutic dosages. During GC treatment, increased hepatic activation of E to F may aggravate metabolic side effects of GCs such as seen in the metabolic syndrome. (c) Georg Thieme Verlag KG Stuttgart . New York.

Page last updated: 2011-12-09

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017