Intra-adipose steroid metabolism may be a key determinant of accumulation and distribution of body fat. Adverse 'central' fat can be driven by glucocorticoid excess or decreased oestrogen/androgen ratio. We previously demonstrated increased regeneration of cortisol by 11beta-HSD1 in adipose in human obesity. Here, we measured mRNAs for enzymes dictating local activation of oestrogens (aromatase) and androgens (5alpha-reductase type 1) in subcutaneous human adipose and related these to adiposity, fat distribution, glucocorticoid metabolism and key steroid-regulated target genes.
With ethical approval, we examined subcutaneous abdominal adipose biopsies from two healthy volunteers cohorts (14 men (M) and 13 women (F) from Northern Sweden and 19 men from Finland), (BMI range 21-36). mRNAs were measured by real time PCR. Data presented as standardised beta coefficients (r) after adjustment for gender and cohort in multiple regression analyses. *p<0.05, **p<0.01, ***p<0.005.
Increased aromatase mRNA was associated with generalised rather than central obesity (for BMI, r=0.51**, % body fat r=0.42*, and waist/hip ratio r=0.11), with higher leptin (r=0.36*) and 11beta-HSD1 (r=0.31***) mRNAs, and with higher 11beta-HSD1 activity (r=0.34**), but not with differences in hormone sensitive lipase, lipoprotein lipase (LPL) or PPAR-gamma. 5alpha-Reductase type 1 mRNA was positively associated with aromatase (r=0.34*, adjusted for BMI), PPAR-gamma(r=0.40*) and LPL (r=0.32*) mRNAs but was not associated with anthropometric variables.
Aromatase deficiency is associated with central obesity in animal and human models. However, we have demonstrated increased aromatase expression in subcutaneous adipose in idiopathic obesity, which does not predict specifically gynoid fat distribution. Increased oestrogen generation may be balanced by associated increased generation of potent 5alpha-reduced androgens. In cell culture, aromatase expression is up-regulated by glucocorticoids, while in some models 11beta-HSD1 is down-regulated by oestrogens. The positive association between aromatase and 11beta-HSD1 mRNAs suggests that increased aromatase may be a consequence rather than cause of increased cortisol regeneration within adipose.