Horenburg S, Fischer-Posovszky P, Debatin K-M, Wabitsch M
Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany.
Horm Metab Res. 2008 Nov;40(11):779-86. doi: 10.1055/s-0028-1083780. Epub 2008 Sep 15.
Adiponectin is an adipokine with profound antidiabetic and antiatherogenic effects. Circulating adiponectin concentrations are higher in women than in men. In order to study the molecular aspects of this sex-specific dimorphism, we examined the expression of adiponectin in human fat cells under the influence of sex hormones, using SGBS cells as an in vitro model. Androgen and estradiol receptor 1 and 2 (AR, ESR1, ESR2) mRNA expression increased dramatically during adipogenic differentiation. Stimulation with human male and female serum led to a downregulation of adiponectin expression, with male serum exerting significantly stronger inhibitory properties than female serum (p<0.05). Increasing concentrations of testosterone or estradiol influenced neither adiponectin mRNA expression and secretion nor intracellular protein expression of high-, middle-, and low-molecular-weight (HMW, MMW, LMW) adiponectin multimers. These data have been verified in in vitro-differentiated primary human adipocytes. We conclude that although human adipocytes express AR, ESR1, and ESR2 and respond to testosterone treatment with a decrease in leptin expression, expression and secretion of adiponectin is unaffected by sex steroids. We hypothesize, therefore, the existence of a serum factor that is differently regulated by sex steroids and subsequently causes the sex dimorphism in circulating adiponectin levels.
脂联素是一种具有显著抗糖尿病和抗动脉粥样硬化作用的脂肪因子。女性循环脂联素浓度高于男性。为了研究这种性别特异性二态性的分子机制，我们以SGBS细胞作为体外模型，检测了性激素影响下人体脂肪细胞中脂联素的表达。雄激素和雌激素受体1和2（AR、ESR1、ESR2）的mRNA表达在脂肪生成分化过程中显著增加。用人男性和女性血清刺激导致脂联素表达下调，男性血清的抑制作用明显强于女性血清（p<0.05）。睾酮或雌二醇浓度的增加既不影响脂联素mRNA的表达、分泌，也不影响高分子量、中分子量和低分子量（HMW、MMW、LMW）脂联素多聚体的细胞内蛋白表达。这些数据已在体外分化的原代人脂肪细胞中得到验证。我们得出结论，虽然人脂肪细胞表达AR、ESR1和ESR2，并且对睾酮治疗有反应，瘦素表达降低，但脂联素的表达和分泌不受性类固醇的影响。因此，我们推测存在一种受性类固醇不同调节的血清因子，随后导致循环脂联素水平的性别二态性。
