Testosterone stimulates adipose tissue 11beta-hydroxysteroid dehydrogenase type 1 expression in a depot-specific manner in children.
BACKGROUND
Activation of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue results in the production of excess tissue glucocorticoids and the induction of adiposity and visceral obesity in particular. Androgens may affect body fat distribution by regulating the local metabolism of cortisol.


OBJECTIVE
Our objective was to study 11beta-HSD1 mRNA expression in abdominal sc and omental (om) adipose tissue in children after in vitro testosterone and cortisol treatment.


METHODS
Paired fat biopsies (sc and om) were obtained from 19 boys (age 6-14 yr, body mass index 14.6-25.3 kg/m(2), BMI sd score SDS -1.6-3.1) undergoing open abdominal surgery. Pieces of adipose tissue were incubated with testosterone, cortisol, or both hormones for 24 h, whereupon mRNA expression of 11beta-HSD1 and hexose-6-phosphate dehydrogenase (H6PDH) were measured by real-time PCR, and 11beta-HSD1 enzyme activity was determined.


RESULTS
Testosterone treatment up-regulated 11beta-HSD1 mRNA expression compared with control incubations in the absence of testosterone (P < 0.05) in om adipose tissue. Testosterone and cortisol both increased 11beta-HSD1 mRNA expression in om but not sc adipose tissue in a depot-specific manner by 2.5- and 2.9-fold, respectively (P < 0.001). However, there was no synergistic effect of the two hormones. 11beta-HSD1 enzyme activity correlated positively to mRNA expression (r = 0.610; P = 0.001). Adipose tissue mRNA expression of H6PDH was affected in a similar fashion to 11beta-HSD1 after hormonal treatment.


CONCLUSIONS
Testosterone and cortisol stimulated 11beta-HSD1 and H6PDH mRNA expression and 11beta-HSD1 activity in om but not in sc adipose tissue. This suggests that these hormones may contribute to fat distribution and accumulation during childhood.
Zhu
Lijun
L
Departments of Children's Health Care, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
Hou
Miao
M
Sun
Bin
B
Burén
Jonas
J
Zhang
Li
L
Yi
Jun
J
Hernell
Olle
O
Li
Xiaonan
X
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D002648:Child; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D013739:Testosterone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D006854:Hydrocortisone