Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys.
OBJECTIVE
The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing's syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1) regenerates active cortisol from inactive cortisone. Altered 11beta-HSD1 may cause tissue-specific Cushing's syndrome with central obesity and impaired glucose homeostasis.


METHODS
Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male and 6 female obese pubertal children (aged 12-18 years, Tanner stages 2-5). In addition, analyses of 24-h excretion rates of glucocorticoids were also performed in 21 age-, sex-, and pubertal stage-matched non-obese children using gas chromatographic-mass spectrometric (GC-MS) analysis.


RESULTS
11beta-HSD1 activity (urinary tetrahydrocortisol (THF) + 5alpha-THF/tetrahydrocortisone (THE) ratio) was lower in obese when compared with non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11beta-HSD1 activity was significantly related to age in lean and obese children. Standard deviation score (SDS)-body mass index did not correlate with 11beta-HSD1 activity, or with total cortisol metabolite excretion within each group. In obese children, 11beta-HSD1 activity and total cortisol metabolite excretion showed no correlation to waist-to-hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index.


CONCLUSIONS
In conclusion, our findings strongly suggest that 11beta-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children have a higher total cortisol metabolites excretion suggesting a stimulated hypothalamus-pituitary-adrenal axis.
Wiegand
Susanna
S
Paediatric Endocrinology, Campus Virchow, Charité University Medicine Berlin, 13353, Berlin, Germany.
Richardt
Anna
A
Remer
Thomas
T
Wudy
Stefan A
SA
Tomlinson
Jeremy W
JW
Hughes
Beverly
B
Grüters
Annette
A
Stewart
Paul M
PM
Strasburger
Christian J
CJ
Quinkler
Marcus
M
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000652:urine*; D000293:Adolescent; D000367:Age Factors; D001837:Body Weights and Measures; D002648:Child; D003348:Cortisone / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005938:Glucocorticoids / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism
D005938:Glucocorticoids; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003348:Cortisone; D006854:Hydrocortisone