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  • Title: 11Beta hydroxysteroid dehydrogenase type 1 is expressed and is biologically active in human skeletal muscle.
    Author: Jang C, Obeyesekere VR, Dilley RJ, Alford FP, Inder WJ.
    Journal: Clin Endocrinol (Oxf); 2006 Dec; 65(6):800-5. PubMed ID: 17121533.
    Abstract:
    OBJECTIVE: No data exist regarding the distribution and oxoreductase enzyme activity of 11beta hydroxysteroid dehydrogenase type 1 (11beta HSD-1) in fresh human skeletal muscle. We aimed to investigate the mRNA and protein expression of 11beta HSD-1 in fresh skeletal muscle, confirm its biological activity and determine its relationship with hexose-6-phosphate dehydrogenase (H6PDH). We also examined the muscle fibre localization of 11beta HSD-1. DESIGN: Eleven non-diabetic community volunteers underwent muscle biopsy of vastus lateralis. MEASUREMENTS: (i) 11beta HSD-1 and H6PDH mRNA expression by quantitative reverse transcription polymerase chain reaction (RT-PCR); (ii) protein localization and fibre type specificity by immunohistochemistry; and (iii) enzyme oxoreductase activity by percentage conversion of 3H cortisone to cortisol. RESULTS: 11beta HSD-1 mRNA was expressed at low levels compared to human liver. Mean DeltaCT of skeletal muscle in 11 subjects was 19.57 (range 18.40-20.79) compared to DeltaCT of 12.75 in human liver, which equates to an approximate 100-fold higher level of expression. H6PDH mRNA was also detected with a mean DeltaCT of 14.46 (range 13.13-16.60), approximately 35-fold more abundant than 11beta HSD-1 in skeletal muscle. There was a significant correlation between 11beta HSD-1 and H6PDH (r = 0.67, P = 0.03). 11beta HSD-1 immunostaining was present in all muscle specimens, with similar distribution among fast and slow twitch fibres. 11beta HSD-1 oxoreductase activity was demonstrated, with mean conversion of cortisone to cortisol of 17.7% per 200 mg of muscle per 24 h (range 7.1-29.5%). CONCLUSIONS: 11beta HSD-1 mRNA and protein is expressed in fresh human skeletal muscle along with readily demonstrable oxoreductase activity. 11beta HSD-1 localization is not muscle fibre type specific. High levels of skeletal muscle H6PDH should ensure that oxoreductase activity predominates in vivo.
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