Background: Obesity in females is often associated with metabolic complications and hyperandrogenism. However, the source of androgens is not entirely clear.
Objectives and hypotheses: Our objective was to find out if adipose tissue (AT) is a site of steroid production during childhood and adolescence, and if this source could add to hyperandrogenism in obese females.
Methods: Parametrial and inguinal adipose tissue was collected and preadipocytes were isolated and cultured from young (day 20) and adult (day 60), lean female rats for gene expression analysis of steroidogenic enzymes and to measure testosterone in AT and in the supernatant of cultured cells. Thin layer chromatography (TLC) was performed on pre- and adipocytes to evaluate the conversion of pregnenolone to other steroids. Steroidogenic gene expression was measured at the transcriptional level by qPCR from AT of lean and obese rats.
Results: We found significant amounts of testosterone in AT from both depots in young animals and adult rats (25 ng to 153 ng/g AT) and in the supernatants of pre- and adipocytes (0.330.69 ng/10000 cells) with the highest values in mature adipocytes of adult rats. Steroidogenic enzymes, including Star, Cyp11A1, Cyp17A1, CYP19, Hsd3b2, Hsd17b3 and 5-alpha-reductase were expressed in AT and isolated cells in culture, from both depots and ages, with higher expression levels in mature adipocytes. TLC data revealed that pre- and adipocytes were able to convert pregnenolone to testosterone and 3-alpha-diol. Finally we analysed expression of steroidogenic enzymes in lean and obese animals and found higher levels for all steroidogenic enzymes in both depots, being significant in inguinal AT (StAR +77.5% P=0.048, Hsd3b2+221% P=0.015, Hsd17b3+280% P=0.009; CYP19+246% P=0.023).
Conclusion: Our study demonstrates that the whole steroidogenic machinery is expressed in AT and that it may serve as an additional site of steroid production. Thus, high levels of androgens in obesity might be produced by AT and thereby add to the vicious circle of metabolic complications in obese females.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology