Endocrine Abstracts

Introduction: Elevated activity and expression of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) are associated with the development of obesity and metabolic syndrome. This enzyme is responsible for majority of the extra-adrenal production of glucocorticoids. It regenerates active cortisol from biologically inactive cortisone. Human 11β-HSD1 also reversibly catalyzes the inter-conversion of 7α-hydroxy- and 7β-hydroxy-DHEA into 7-oxo-DHEA. In order to examine the role of 11β-HSD1 in human obesity, we followed the circulating levels of steroids related to 11β-HSD1 in obese patients and non-obese controls.

Methods/design: The cohort of 282 obese adolescents, 154 girls (median age 15.31, range 14.17–16.68 years) and 128 boys (median age 14.95, range 13.87–16.16 years), BMI >90th percentile and the cohort of 100 normostenic controls including 50 girls (median age 15.29, range 14.32–16.79 years) and 50 boys (median age 15.29, range 14.47–16.77 years), BMI 25th–75th percentiles were examined. Circulating levels of cortisol, cortisone, DHEA, 7-oxo-, 7α-hydroxy-, 7β-hydroxy-, and 16α-hydroxy-DHEA were analysed by liquid chromatography-tandem mass spectrometry method.

Results: We found significantly increased levels of cortisone in obese subjects, while cortisol levels did not differ between obese and normostenic adolescents. Higher circulating levels of DHEA in obese girls, higher 7β-hydroxy-DHEA in both sexes, higher 7-oxo-DHEA in obese boys and reduced levels of 16α-hydroxy-DHEA in obese girls were observed. While the absolute levels of circulating 7α-hydroxy-DHEA did not differ between examined groups, the 7α-hydroxy-DHEA/DHEA ratio was significantly lower in obese subjects suggesting reduced 7α-hydroxylation in obesity.

Conclusion: Our findings support a role of 11β-HSD1 as well as derivatives of DHEA in the control of human metabolism.

Disclosure: This work was supported by IGA MZCR NT/13542-3 and MH CZ – DRO (Institute of Endocrinology – EU, 00023761).