Down-regulation of hepatic and renal 11 beta-hydroxysteroid dehydrogenase in rats with liver cirrhosis

Gastroenterology
G EscherF J Frey

Abstract

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) enzymes are responsible for the interconversion of active 11 beta-hydroxycorticosteroids into inactive 11-ketoglucocorticosteroids and by that mechanism regulate the intracellular access of the steroids to the cognate receptor. A down-regulation of the shuttle of active to inactive glucocorticoids enhances access of glucocorticosteroids to both the glucocorticoid and the mineralocorticoid receptors. In liver cirrhosis, enhanced mineralocorticoid and glucocorticoid effects are observed. We therefore investigated the impact of liver cirrhosis after bile duct ligation on the transcription and activity of 11 beta-OHSD1 and 11 beta-OHSD2 in the corresponding tissues. Messenger RNA from 11 beta-OHSD1 and 11 beta-OHSD2 was assessed by reverse-transcription polymerase chain reaction; activity was assessed by measuring the interconversion of corticosterone to dehydrocorticosterone. The effect of bile and bile salts was determined using COS-1 cells transfected with 11 beta-OHSD1 or 11 beta-OHSD2. In liver tissue, the messenger RNA ratios of 11 beta-OHSD1 to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) levels and, in kidney tissue, the ratios of 11 beta-OHSD2 to GAPDH levels decrease...Continue Reading

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Citations

Aug 26, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D AckermannF J Frey
Jul 20, 1999·Molecular and Cellular Endocrinology·Z Krozowski
Jul 12, 2001·Journal of Gastroenterology and Hepatology·T G van RossumS W Schalm
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Sep 29, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Felix J Frey
Aug 22, 2006·Cancer Science·Kazunari TsujimuraTomoyuki Shirai
Jun 29, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Daniel AckermannAlain Doucet
Dec 4, 2003·Expert Opinion on Therapeutic Targets·Brian R Walker, Jonathan R Seckl
Nov 7, 2001·The Journal of Clinical Investigation·C QuattropaniF J Frey
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Aug 1, 2013·Physiological Reviews·Karen ChapmanJonathan Seckl
Aug 19, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Helle C ThiessonOle Skøtt

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