Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes

被引:347
|
作者
Xu, AM
Chan, KW
Hoo, RLC
Wang, Y
Tan, KCB
Zhang, JL
Chen, BY
Lam, MC
Tse, C
Cooper, GJS
Lam, KSL
机构
[1] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China
[2] Univ Hong Kong, Res Ctr Heart Brain Hormone & Hlth Aging, Hong Kong, Hong Kong, Peoples R China
[3] Univ Hong Kong, Genome Res Ctr, Hong Kong, Hong Kong, Peoples R China
[4] Univ Auckland, Ctr Mol Biodiscovery, Auckland 1020, New Zealand
关键词
D O I
10.1074/jbc.M414231200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:18073 / 18080
页数:8
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