Using a three-dimensional (3-D) culture model, we report the dose dependent effect of 17β-estradiol and testosterone on the adipogenic differentiation and maturation of human adipose derived stem cells (hASCs) obtained from female and male patients. Considering sexual dimorphism, we expected male and female adipocytes to respond differently to the sex steroids. Both male and female hASC spheroids were exposed to 100 nM and 500 nM of 17β-estradiol and testosterone either at the beginning of the adipogenic maturation (Phase I) to discourage intracellular triglyceride accumulation or exposed after adipogenic maturation (Phase II) to reduce the intracellular triglyceride accumulation. The results show that 17β-estradiol leads to a dose dependent reduction in intracellular triglyceride accumulation in female hASC spheroids compared to the both untreated and testosterone-treated cells. Affirming our hypothesis, 17β-estradiol prevented intracellular triglyceride accumulation during Phase I, while it stimulated lipolysis during Phase II. PPAR-γ and adiponectin gene expression also reduced upon 17β-estradiol treatment in female cells. Interestingly, 17β-estradiol and testosterone had only a modest effect on the male hASC spheroids. Collectively, our findings suggest that 17β-estradiol can prevent fat accumulation in adipocytes during early and late stages of maturation in females.

中文翻译：

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性别二态性对脂肪生成的影响：用 17β-雌二醇和睾酮处理的三维体外模型

使用三维 (3-D) 培养模型，我们报告了 17β-雌二醇和睾酮对从女性和男性患者获得的人类脂肪干细胞 (hASC) 的脂肪形成分化和成熟的剂量依赖性影响。考虑到性别二态性，我们预计男性和女性脂肪细胞对性类固醇的反应不同。雄性和雌性 hASC 球体在成脂成熟开始时（第一阶段）暴露于 100 nM 和 500 nM 的 17β-雌二醇和睾酮，以阻止细胞内甘油三酯积累，或在成脂成熟（第二阶段）后暴露于17β-雌二醇和睾酮，以减少细胞内甘油三酯的积累。甘油三酯积累。结果表明，与未处理和睾酮处理的细胞相比，17β-雌二醇导致雌性 hASC 球体细胞内甘油三酯积累的剂量依赖性减少。证实了我们的假设，17β-雌二醇在第一阶段阻止了细胞内甘油三酯的积累，而在第二阶段刺激了脂肪分解。在雌性细胞中，17β-雌二醇处理后，PPAR-γ 和脂联素基因表达也降低。有趣的是，17β-雌二醇和睾酮对雄性 hASC 球体的影响不大。总的来说，我们的研究结果表明，17β-雌二醇可以防止女性成熟早期和晚期脂肪细胞中的脂肪积累。