Xu Aimin, Chan Kok Weng, Hoo Ruby L C, Wang Yu, Tan Kathryn C B, Zhang Jialiang, Chen Baoying, Lam Michael C, Tse Cynthia, Cooper Garth J S, Lam Karen S L
Department of Medicine and Research Center of Heart, Brain, Hormone, and Healthy Aging, University of Hong Kong, Hong Kong, China.
J Biol Chem. 2005 May 6;280(18):18073-80. doi: 10.1074/jbc.M414231200. Epub 2005 Mar 9.
The antidiabetic hormone adiponectin circulates in blood as several oligomeric complexes, and the ratios between them are critical in determining insulin sensitivity. In this study we investigated the role of testosterone in regulating the oligomeric complex distribution of adiponectin. Gel filtration analysis revealed that circulating adiponectin existed as the forms of high molecular weight (HMW), middle molecular weight, and low molecular weight complexes in both human and mice. The concentration of HMW adiponectin in female was significantly higher than that in male, whereas there were no gender differences for the other two forms. Castration induced a dramatic elevation of the HMW form but had no effect on either the middle molecular weight or the low molecular weight form in mice. Testosterone treatment, on the other hand, caused a specific reduction of HMW adiponectin in the circulation. Pulse-chase labeling experiments in rat adipocytes revealed that the three oligomeric forms of adiponectin were secreted into the culture medium at different rates and that testosterone selectively impeded the secretion of HMW adiponectin but not the other two forms. The inhibitory effect of testosterone on secretion of HMW adiponectin was largely restored by the transcription inhibitor actinomycin D, suggesting the involvement of a transcriptional event in this process. The selective inhibition of HMW adiponectin by testosterone might contribute to the sex dimorphism of adiponectin in terms of its oligomeric complex distribution and could partly explain why men have higher risk to insulin resistance and atherosclerosis than women.
抗糖尿病激素脂联素以多种寡聚体复合物的形式在血液中循环，它们之间的比例对于确定胰岛素敏感性至关重要。在本研究中，我们调查了睾酮在调节脂联素寡聚体复合物分布中的作用。凝胶过滤分析显示，在人类和小鼠中，循环中的脂联素均以高分子量（HMW）、中分子量和低分子量复合物的形式存在。女性中HMW脂联素的浓度显著高于男性，而其他两种形式则无性别差异。去势导致小鼠中HMW形式显著升高，但对中分子量或低分子量形式没有影响。另一方面，睾酮治疗导致循环中HMW脂联素特异性减少。大鼠脂肪细胞的脉冲追踪标记实验表明，脂联素的三种寡聚体形式以不同速率分泌到培养基中，并且睾酮选择性地阻碍HMW脂联素的分泌，而不影响其他两种形式。睾酮对HMW脂联素分泌的抑制作用在很大程度上被转录抑制剂放线菌素D恢复，表明该过程涉及转录事件。睾酮对HMW脂联素的选择性抑制可能在脂联素寡聚体复合物分布方面导致其性别二态性，并且可以部分解释为什么男性比女性患胰岛素抵抗和动脉粥样硬化的风险更高。
