Expression of 11beta-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome.
OBJECTIVE
To investigate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity.


METHODS
Cross-sectional study.


METHODS
A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age- and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR.


RESULTS
Polycystic ovary syndrome (P<0.05) and obesity (P<0.05) were independently associated with increased expression of 11beta-HSD1 mRNA. The subgroups LP and OC had increased 11beta-HSD1 and 11beta-HSD2 mRNA expression compared with LC (P<0.05, P<0.05). There were no effects of PCOS or obesity on11beta-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (P<0.001) and increased upper body fat distribution (P<0.01) were associated with increased expression of 11beta-HSD1, but neither 11beta-HSD2 nor H6PDH.


CONCLUSIONS
Polycystic ovary syndrome and obesity are independently associated with increased expression of 11beta-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11beta-HSD1.
Svendsen
P F
PF
Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Hvidovre, Denmark. pernille.svendsen@hvh.regionh.dk
Madsbad
S
S
Nilas
L
L
Paulsen
S K
SK
Pedersen
S B
SB
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D015502:Absorptiometry, Photon; D000328:Adult; D000704:Analysis of Variance; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D009765:Obesity / Q000201:enzymology*; D011085:Polycystic Ovary Syndrome / Q000201:enzymology*; D050151:Subcutaneous Fat / Q000201:enzymology*; D013851:Thinness / Q000201:enzymology*
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2