ESPE Abstracts

Background: Obesity in females is often associated with metabolic complications and hyperandrogenism but the role of adipose tissue (AT) in androgen synthesis remains unclear.

Aims/Objectives: Employing human subcutaneous and visceral AT and cultured adipocytes, we studied whether AT could be a source of androgens promoting hyperandrogenism in lean and especially in obese females.

Methods: Subcutaneous and visceral AT was collected during elective surgeries from lean and obese patients and from females undergoing bariatric surgery. Hormone levels were measured in serum. Furthermore androgens were measured by Mass-Spec analysis in the supernatants of cultured human preadipocytes and adipocytes, and in extracts from subcutaneous and visceral AT. Gene and protein expression of steroidogenic enzymes were determined in AT and in cultured cells.

Results: Obese females had elevated androgen levels (e.g. testosterone, androstenedione, DHEAs, and T-SHBG-quotient) in serum compared to lean females. Serum androgen levels were reduced in patients with weight loss after bariatric surgery. We found substantial amounts of testosterone in subcutaneous and visceral AT from lean and obese females (9.11 –12.3ng/g tissue) being significantly higher in visceral tissue of obese females (+35%, P=0.024) and in the supernatant of preadipocytes and adipocytes (0.22-0.55ng/10.000cells). Furthermore, Mass-Spec revealed that progesterone, testosterone, DHT and androstenedione were measurable in AT of both depots and cell culture supernatant of preadipocytes and adipocytes in culture. Measured steroids were higher in samples from obese females, with the highest difference for testosterone in visceral tissue (+687%, P=0.032). Steroidogenic enzymes, including StAR, Cyp11A1, Cyp17A1, Cyp19, Hsd3b2, Hsd17b3/6, CYP19, AR, LH-receptor, AKR1C2 and 3 and 5alpha-reductase I and II were expressed in most of the human AT samples and cultured adipocytes from both depots. We found a significantly higher expression of CYP19 in visceral AT of obese females. Furthermore we found depot-specific differences for the expression of the following genes: StAR, Hsd3b2, Hsd17b6, Cyp19 and AR. Interestingly AKR1c2 and 3 were highly expressed in both depots in lean and obese females with a highly significant upregulation in obese individuals. Therefore the backdoor pathway for steroidogenesis might be a new mechanism and pathway for hyperandrogenism in obese females.

Conclusion: The whole steroidogenic machinery of the classical and backdoor pathway of steroidogenesis and capacity for androgen biosynthesis were found in both AT depots and cultured preadipocytes and adipocytes. Therefore, we hypothesize that AT is a de-novo site of androgen production and hence might add to the hyperandrogenism and irregular cycles in obese females.