title: Reduced levels of circulating 7alpha-hydroxy-dehydroepiandrosterone in treated adolescent obese patients.
abstract: Elevated levels of glucocorticoids lead to the development of obesity and metabolic syndrome. Local glucocorticoid levels are regulated through the enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD 1), an enzyme that regenerates active cortisol from inert cortisone. Increased expression of 11beta-HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Human 11beta-HSD 1 is also responsible for inter-conversion of 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form. To better understanding the mechanism of the action, we focused on 7-OH- and 7-oxo-DHEA, and their circulating levels during the reductive treatment in adolescent obese patients. We determined plasma levels of 7alpha-OH-DHEA, 7beta-OH-DHEA, and 7-oxo-DHEA in 55 adolescent patients aged 13.04-15.67 years, BMI greater than 90th percentile. Samples were collected before and after one month of reductive therapy. Circulating levels of 7alpha-OH-DHEA decreased during the reductive therapy from 1.727 (1.614; 1.854, transformed mean with 95 % confidence interval) to 1.530 nmol/l (1.435; 1.637, p<0.05) in girls and from 1.704 (1.583; 1.842) to 1.540 nmol/l (1.435; 1.659, p<0.05) in boys. With regard to the level of 7-oxo-DHEA, a significant reduction from 1.132 (1.044; 1.231) to 0.918 nmol/l (0.844; 1.000, p<0.05) was found after the treatment, but only in boys. No significant difference in 7beta-OH-DHEA levels was observed. In conclusions, diminished levels of 7alpha-OH-DHEA indicate its possible effect on activity of 11beta-HSD 1. Further studies are necessary to clarify whether competitive substrates for 11beta-HSD 1 such as 7alpha-OH-DHEA could inhibit production of glucocorticoids and may be involved in metabolic processes leading to reduction of obesity.
authors.affiliation: Department of Steroids and Proteofactors, Institute of Endocrinology, Prague, Czech Republic. lmacova@endo.cz.
authors.forename: L
authors.initials: L
authors.lastname: Máčová
authors.forename: M
authors.initials: M
authors.lastname: Bičíková
authors.forename: H
authors.initials: H
authors.lastname: Zamrazilová
authors.forename: M
authors.initials: M
authors.lastname: Hill
authors.forename: H
authors.initials: H
authors.lastname: Kazihnitková
authors.forename: B
authors.initials: B
authors.lastname: Sedláčková
authors.forename: L
authors.initials: L
authors.lastname: Stárka
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D031204:Caloric Restriction / Q000379:methods / Q000639:trends; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009765:Obesity / Q000097:blood* / Q000628:therapy*; D016896:Treatment Outcome; D061217:Weight Reduction Programs / Q000379:methods / Q000639:trends*
chemical_list: D015415:Biomarkers; D003687:Dehydroepiandrosterone; C003587:7-hydroxydehydroepiandrosterone