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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 …