Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, insulin resistance, and androgen excess in women. Adipose androgen generation of testosterone from androstenedione by aldo-ketoreductase type 1C3 (AKR1C3) may contribute to hyperandrogenism, particularly in the setting of obesity. We aimed to determine the effects of BMI and age on AKR1C3 expression in subcutaneous (SC) and omental (OM) fat depots in both women and men.

Paired SC and OM samples were obtained from men and women undergoing abdominal surgery at the Queen Elizabeth Hospital Birmingham. Baseline demographic data including age and BMI was collected. RNA was extracted; after RT, AKR1C3 mRNA expression was determined by realtime quantitative PCR. Pearson’s correlation testing was used to determine relationships between variables.

Paired SC and OM samples from 38 women and 23 men (total 122 samples) were analysed (mean age 56.4±1.7 and 60±2.6 years respectively). Mean BMI was 28.8±0.8 kg/m² in women and 27.8±0.5 kg/m² in men. AKR1C3 expression (ΔCT) was similar in men and women (8.1±0.5 and 8.3±0.6 respectively). Expression was significantly higher in SC compared to OM fat (7.1±0.6 vs 9.2±0.4, P=0.004), and in obese compared to non-obese women (6.4±1.1 vs 8.9±0.4, P=0.01). BMI had a strong positive correlation with SC adipose AKR1C3 expression in women (R=−0.51 for ΔCT, P=0.006); this association was not observed in men or in omental fat. AKR1C3 expression declined with age in men but not women (R=0.61 for ΔCT, P=0.009).

We have found evidence of depot- and sex-specific regulation of AKR1C3 by BMI and age in human adipose tissue. Subcutaneous AKR1C3 expression is upregulated in obesity in females. Obesity may drive adipose androgen generation in PCOS through this pathway.