11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mRNA expression in liver of patients with non-alcoholic steatohepatitis

Sarah Konopelska; Tina Kienitz; Matthias Pirlich; Jürgen Bauditz; Paul M. Stewart; Herbert Lochs; Christian J. Strasburger; Marcus Quinkler

OC10.2

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Endocrine Abstracts (2007) 14 OC10.2

ECE2007 Oral Communications Obesity & metabolism (7 abstracts)

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mRNA expression in liver of patients with non-alcoholic steatohepatitis

Sarah Konopelska ¹ , Tina Kienitz ¹ , Matthias Pirlich ¹ , Jürgen Bauditz ¹ , Paul M. Stewart ² , Herbert Lochs ¹ , Christian J. Strasburger ¹ & Marcus Quinkler ¹

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¹Internal Medicine, Center for Gastroenterology, Hepatology and Endocrinology, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin, Germany; ²Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom.

Background: Non-alcoholic fatty liver disease (NAFLD) is recognized as common liver disorder that represents the hepatic manifestation of the metabolic syndrome including visceral obesity, type 2 diabetes, insulin resistance and hyperlipidemia. Non-alcoholic steatohepatitis (NASH) is the progressive form of liver injury with the risk for progressive fibrosis, cirrhosis and end-stage liver disease. The pathophysiology that leads to NAFLD and NASH is not well understood. We hypothesize that an altered cortisol metabolism in the liver may be a pathogenetic factor. Hepatic 11beta-HSD1 regenerates cortisol from its inactive metabolite cortisone and requires NADPH as cosubstrate, which is supplied by hexose-6-phosphate-dehydrogenase (H6PDH).

Methods: 76 patients (29 men, 48 women) underwent liver biopsy due to elevated liver enzymes. We quantified 11beta-HSD1 and H6PDH mRNA expression by real-time PCR with 18S as housekeeping gene using a BioRad iCycler. In addition, anthropometric measurements and analysis of 24 hour excretion rates of glucocorticoids using gas chromatographic-mass spectrometric (GC-MS) analysis were performed.

Results: 11beta-HSD1 mRNA expression correlated significantly (r²=0.803; P<0.001) with H6PDH mRNA expression. We detected a significant correlation between 11beta-HSD1 mRNA expression and waist-to-hip ratio (r²=0.211; P<0.05), but not to urinary (THF+5alphaTHF)/THE ratio, total cortisol metabolite excretion, age or BMI. No gender specific differences were seen in mRNA gene expression.

Discussion: Our data suggest that 11beta-HSD1 gene expression highly depends on H6PDH gene expression. Surprisingly, 11beta-HSD1 gene expression did not correlate with any urinary glucocorticoid ratio showing the limitation of urinary analysis. In our patient’s cohort a higher waist-to-hip-ratio (abdominal obesity) was associated with a lower 11beta-HSD1 mRNA expression in the liver.