Gender-specific links between hepatic 11 beta reduction of cortisone and adipokines

Objective: Reduction of cortisone to cortisol is mediated by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-alpha (TNF-alpha), are of importance for 11 beta HSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-a receptors and/or sex hormones. Research Methods and Procedures: A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood Sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11 beta HSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol. Results: Hepatic 11 beta HSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-alpha receptors also after adjustment of BMI and waist circumference. In contrast, 11 beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference. Discussion: Hepatic 11 beta reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11 beta HSD1 in both genders.