11β hydroxysteroid dehydrogenase type 1 is expressed and is biologically active in human skeletal muscle

Objective No data exist regarding the distribution and oxoreductase enzyme activity of 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD-1) in fresh human skeletal muscle. We aimed to investigate the mRNA and protein expression of 11 beta 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 11 beta HSD-1. Design Eleven non-diabetic community volunteers underwent muscle biopsy of vastus lateralis. Measurements (i) 11 beta 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 H-3 cortisone to cortisol. Results 11 beta HSD-1 mRNA was expressed at low levels compared to human liver. Mean Delta C-T of skeletal muscle in 11 subjects was 19.57 (range 18.40-20.79) compared to Delta C-T 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 Delta C-T of 14.46 (range 13.13-16.60), approximately 35-fold more abundant than 11 beta HSD-1 in skeletal muscle. There was a significant correlation between 11 beta HSD-1 and H6PDH (r = 0.67, P = 0.03). 11 beta HSD-1 immunostaining was present in all muscle specimens, with similar distribution among fast and slow twitch fibres. 11 beta 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 11 beta HSD-1 mRNA and protein is expressed in fresh human skeletal muscle along with readily demonstrable oxoreductase activity. 11 beta HSD-1 localization is not muscle fibre type specific. High levels of skeletal muscle H6PDH should ensure that oxoreductase activity predominates in vivo.