The Impact of Reducing Therapy on the Activity of 11beta-hydroxysteroid Dehydrogenase Type 1 in Children

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 677-696-Obesity Physiology & Epidemiology
Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-695
Ludmila Macova*1, Marie Bicikova1, Hana Zamrazilova1, Karel Pacak2 and Luboslav Starka1
1Institute of Endocrinology, Prague, Czech Republic, 2National Institutes of Health (NIH), Bethesda, MD
Objective: Glucocorticoids (GC) are involved in a wide variety of metabolic processes, and their elevated levels lead to the development of dozens of disorders, such as obesity and metabolic syndrome. GC levels are regulated through the hypothalamic-pituitary-adrenal axis and through the local production of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD 1), an enzyme that regenerates active cortisol from inactive cortisone. Elevated expression of 11β-HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Therefore, specific inhibitors of the enzyme 11β-HSD 1 are considered to be an effective treatment option for the obesity and metabolic syndrome. Human 11β-HSD 1 acts also as a steroid oxido-reductase that converts the 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form and vice versa. The 7-OH-DHEA metabolites are known for their anti-glucocorticoid and anti-dietary effects, but the mechanism of the action remains unclear. The aim of this study is to contribute to the clarification of the role of 7-OH metabolites of DHEA as new hormonal factors that influence obesity in juvenile patients.

Methods: We investigated serum levels of cortisol, cortisone, 7α-OH-DHEA, 7β-OH-DHEA, and 7-oxo-DHEA in 30 adolescent patients aged 12-17.9 years, BMI˃90th percentile. Samples were collected before and after one month of reducing therapy.

Results: We found reduced levels of cortisol as well as 7-oxo-DHEA associated with lower BMI after reducing therapy. No significant differences in other steroid levels were observed.

Conclusions: We found a positive correlation between diminished levels of 7-oxo-DHEA, cortisol, and weight loss. These results indicate that metabolites of DHEA might affect the enzymatic activity of 11β-HSD 1. Further studies are needed to determine whether competitive substrates for 11β-HSD 1 (as metabolites of DHEA) inhibit production of GC. If so, they may provide a new therapeutic strategy for metabolic disorders such as obesity and metabolic syndrome.

Nothing to Disclose: LM, MB, HZ, KP, LS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The study was supported by grant NT 13542-3/2012 of the Internal Grant Agency of the Czech Ministry of Health.