Androgens Decrease Plasma Adiponectin, an Insulin-Sensitizing Adipocyte-Derived Protein
- Hitoshi Nishizawa,
- Iichiro Shimomura,
- Ken Kishida,
- Norikazu Maeda,
- Hiroshi Kuriyama,
- Hiroyuki Nagaretani,
- Morihiro Matsuda,
- Hidehiko Kondo,
- Naoki Furuyama,
- Shinji Kihara,
- Tadashi Nakamura,
- Yoshihiro Tochino,
- Tohru Funahashi and
- Yuji Matsuzawa
- From the Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Japan
Abstract
Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 ± 11.9 years [mean ± SD]) than in 137 women (53.2 ± 12.0 years) but not different between pre- and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high levels of plasma adiponectin were found in castrated mice. Testosterone treatment reduced plasma adiponectin concentration in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone reduced adiponectin secretion into the culture media, using pulse-chase study. Castration-induced increase in plasma adiponectin was associated with a significant improvement of insulin sensitivity. Our results indicate that androgens decrease plasma adiponectin and that androgen-induced hypoadiponectinemia may be related to the high risks of insulin resistance and atherosclerosis in men.
Footnotes
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Address correspondence and reprint requests to Iichiro Shimomura, Department of Organismal Biosystems, Graduate School of Frontier Bioscience, Department of Medicine and Pathophysiology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: ichi{at}imed2.med.osaka-u.ac.jp.
Received for publication 19 January 2002 and accepted in revised form 22 May 2002.
5α-DHT, 5α-dihydrotestosterone; DMEM, Dulbecco’s modified Eagle’s medium; ELISA, enzyme-linked immunosorbent assay; HOMA-IR, homeostasis model assessment insulin resistance; IPB, immunoprecipitation buffer; NP-40, Nonidet P-40; PMSF, phenylmethylsulfonyl fluoride; TNF, tumor necrosis factor.
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