Supplementary Material for: De-novo and depot-specific androgen production in human adipose tissue - a source of hyperandrogenism in women with obesity

Introduction: Obesity in women is often associated with hyperandrogenism but the role of adipose tissue (AT) in androgen synthesis remains unclear. Therefore, we studied whether AT could be a source of androgens promoting hyperandrogenism. Methods: Subcutaneous and visceral AT was collected from lean and obese women. Androgen levels were evaluated in serum, AT and cell culture supernatant. Gene and protein expression of steroidogenic enzymes were determined. Results: Obese subjects had elevated serum androgen levels, which reduced after weight loss. Androgens were measurable in AT and in cell culture supernatants of adipocytes. Steroids were higher in AT from obese women, with the highest difference for testosterone in visceral AT (+7.9 fold, p=0.032). Steroidogenic enzymes were expressed in human AT with depot-specific differences. Obese women showed a significantly higher expression of genes of the backdoor pathway and of CYP19 in visceral AT. Conclusion: The whole steroidogenic machinery of the classical and backdoor pathways of steroidogenesis, and the capacity for androgen biosynthesis, were found in both AT depots and cultured adipocytes. Therefore, we hypothesize that AT is a de novo site of androgen production and the backdoor pathway of steroidogenesis might be a new pathomechanism for hyperandrogenism in women with obesity.

引言：女性肥胖常与高雄激素血症相关，但脂肪组织（adipose tissue, AT）在雄激素合成中的作用仍不明确。为此本研究探讨AT是否可作为促进高雄激素血症的雄激素来源。
方法：从体重正常及肥胖女性体内采集皮下及内脏脂肪组织。检测血清、AT及细胞培养上清液中的雄激素水平，并测定类固醇生成酶的基因与蛋白表达情况。
结果：肥胖受试者血清雄激素水平升高，且该水平在体重减轻后有所下降。AT及脂肪细胞的细胞培养上清液中均可检测到雄激素。肥胖女性的AT内类固醇水平更高，其中内脏AT中的睾酮差异最为显著（升高7.9倍，p=0.032）。人类AT中存在类固醇生成酶的表达，且存在部位特异性差异。肥胖女性的内脏AT中，后门通路相关基因及CYP19的表达水平显著升高。
结论：本研究在两类脂肪库AT及培养的脂肪细胞中，均检测到类固醇合成经典通路与后门通路的全套合成装置，以及雄激素生物合成能力。据此我们提出假说：AT是雄激素产生的全新位点，而类固醇合成后门通路可能是肥胖女性高雄激素血症的全新致病机制。