Altered glucocorticoid metabolism in girls with central obesity

Abstract

Background: Dysregulation of glucocorticoid metabolism is known to be a causative factor of obesity. However, only a few studies have evaluated the enzymatic activities involved in glucocorticoid metabolism in the pediatric population. Objective: To examine whether circulating glucocorticoid metabolites and their ratios reflecting the activities of metabolic enzyme are associated with obesity and body composition in girls. Methods: A total of 227 girls aged 7-13 years (131 control, 45 overweight, 51 obese) were enrolled in this study. Serum concentrations of glucocorticoids (11-deoxycortisol, cortisol, tetrahydrocortisol [THF], allo-THF, allodihydrocortisol [allo-DHF], and cortisone) were evaluated by gas chromatography-mass spectrometry. Enzyme activities corresponding to the ratios of cortisol and cortisone to their respective precursors and metabolites were also assessed. Results: Serum levels of allo-THF were significantly higher in obese girls compared with those in overweight and control girls (P = 0.018); however, concentrations of other cortisol metabolites were not significantly different between the groups studied. According to the severity of obesity, increasing trends in the metabolic ratios reflecting the activity of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) [(cortisol + allo-DHF + allo-THF + THF)/cortisone], relative 5 alpha/5 beta-reductase [allo-THF/THF] activity, and 3 alpha-HSD [allo-THF/allo-DHF] activity, were noted (P-for-trend <0.05). Body fat percentage and waist-to-height ratio positively correlated with the activities of 11 beta-HSD1 and 3 alpha-HSD (P < 0.05). Following covariate control, girls with central obesity demonstrated significantly higher metabolic ratios reflecting 11 beta-HSD1, relative 5 alpha/5 beta-reductase, and 3 alpha-HSD activities (P < 0.05). Conclusions: We found an altered glucocorticoid metabolism suggesting increased production of cortisol by 11 beta-HSD1 and increased metabolic clearance of cortisol catalyzed by 3 alpha-HSD in girls with central obesity.