Horm Metab Res 2011; 43(1): 66-71
DOI: 10.1055/s-0030-1267170
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

In Vivo Activity of 11β-Hydroxysteroid Dehydrogenase Type 1 in Man: Effects of Prednisolone and Chenodesoxycholic Acid

S. Diederich1 , 2 , M. Quinkler3 , K. Mai1 , M. Schöneshöfer4 , V. Baehr1 , A. Pfeiffer1 , W. Oelkers1 , 2 , E. Eigendorff1
  • 1Department of Endocrinology, Diabetes and Nutrition, Charité Campus Benjamin Franklin, Berlin, Germany
  • 2Endokrinologikum Berlin, Centre for Endocrine and Metabolism Diseases, Berlin, Germany
  • 3Clinical Endocrinology, Centre for Internal Medicine, Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Berlin, Germany
  • 4Department of Clinical Chemistry, Krankenhaus Berlin-Spandau, Berlin, Germany
Further Information

Publication History

received 25.06.2010

accepted 31.08.2010

Publication Date:
05 October 2010 (eFirst)

Abstract

The 11β-hydroxysteroid dehydrogenases (11β-HSDs) play a pivotal role in glucocorticoid (GC) action. 11β-HSD1 is a predominant reductase, activating GCs from inert metabolites, whereas 11β-HSD2 is a potent dehydrogenase inactivating GCs. Knowing the metabolic effects of GCs, a selective inhibition of 11β-HSD1 represents a potential target for therapy of impaired glucose tolerance, insulin insensitivity and central obesity. In vitro, 11β-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 11β-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 11β-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 11β-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 11β-HSD1, which could not be extinguished by a parallel increase of IGF-1 under prednisolone. CDCA does not affect in vivo activity of 11β-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.

References

Correspondence

S. Diederich

Endokrinologikum Berlin am

Gendarmenmarkt

Centre for Endocrine and

Metabolism Diseases

Friedrichstraße 76 (Q207)

10117 Berlin

Phone: +49/30/2091 562 290

Fax: +49/30/2091 562 291

Email: sven.diederich@endokrinologikum.com