Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, hyperinsulinaemia, and androgen excess. Adipose androgen generation of testosterone from androstenedione by aldo-ketoreductase type 1C3 (AKR1C3) may contribute to hyperandrogenism. We hypothesised that insulin may upregulate adipose AKR1C3 expression in vitro in a human differentiated preadipocyte cell line.

We analysed AKR1C3 expression in the SGBS human preadipocyte cell line. Preadipocytes were differentiated into adipocytes under optimised conditions over 14 days. Differentiated adipocytes were exposed to increasing concentrations of insulin, androstenedione, and testosterone in serum-free media for 20 h. We used real-time quantitative PCR to determine gene expression in SGBS cells across differentiation (days 0, 7, and 14) and after acute insulin treatment. Experiments were performed in triplicate. Data are expressed as mean±S.E.M. for delta CT (dCT).

Markers of adipogenesis PPARγ and LPL increased significantly across differentiation. Expression of AKR1C3 also increased across differentiation (dCT day 0, 13.3±0.1; day 14, 7.9±0.9, P=0.01). Acute insulin treatment significantly increased gene expression of AKR1C3 in a dose-dependent manner (insulin 10 mM, dCT 7.3±0.1; insulin 20 mM, dCT 6.5±0.1, P<0.05 for both compared to control, P=0.02 between treatments). Co-incubation of insulin with androstenedione and testosterone significantly reduced AKR1C3 expression compared to insulin alone, P=0.03 and P=0.01 respectively.

AK1C3 expression in a differentiated human preadipocyte cell line is upregulated by insulin. Adipose tissue may be a key site of cross-talk between insulin signalling and androgen metabolism. Local adipose androgen generation in PCOS may be increased in hyperinsulinaemic conditions, and represent a possible target for therapeutic intervention.