Gender-specific links between hepatic 11beta reduction of cortisone and adipokines.
OBJECTIVE
Reduction of cortisone to cortisol is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), 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 11betaHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-alpha receptors and/or sex hormones.


METHODS
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 11betaHSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol.


RESULTS
Hepatic 11betaHSD1 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, 11beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference.


CONCLUSIONS
Hepatic 11beta 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 11betaHSD1 in both genders.
Mattsson
Cecilia
C
Department of Public Health and Clinical Medicine, Umeå University Hospital, S-901 85 Umeå, Sweden. cecilia.mattsson@medicin.umu.se
Rask
Eva
E
Carlström
Kjell
K
Andersson
Jonas
J
Eliasson
Mats
M
Ahrén
Bo
B
Söderberg
Stefan
S
Olsson
Tommy
T
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D003348:Cortisone / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007328:Insulin; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003348:Cortisone