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人类前脂肪细胞中雄激素受体和双氢睾酮代谢的内在区域差异。

Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes.

作者信息

Joyner J, Hutley L, Cameron D

机构信息

Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Ipswich Road, Wolloongabba 4102, Queensland, Australia.

出版信息

Horm Metab Res. 2002 May;34(5):223-8. doi: 10.1055/s-2002-32144.

Abstract

Androgens play an important role in regulating the central obesity that is a strong risk factor for cardiovascular disease and insulin resistance. This study confirms that androgen receptors are present in subcultured human preadipocytes, with androgen receptor gene expression and saturable specific dihydrotestosterone binding, dissociation constant 1.02 - 2.56 nM and maximal binding capacity 30.8 - 55.7 fmol/mg protein. There was an intrinsic regional difference in androgen receptor complement, with more androgen receptors in visceral than in subcutaneous preadipocytes. Dihydrotestosterone was metabolised by human preadipocytes, with more androstanediol produced by subcutaneous than visceral preadipocytes. While dihydrotestosterone metabolism was insufficient to explain the regional variation in androgen binding, both of these differences would reduce the androgen responsiveness of the subcutaneous preadipocytes compared with visceral preadipocytes. There were no gender differences in androgen binding or metabolism. While the direct effects of androgens on human PAs remain uncertain, these regional differences suggest that AR-mediated regulation of certain PA functions influences adipose tissue distribution.

摘要

雄激素在调节中心性肥胖方面发挥着重要作用,而中心性肥胖是心血管疾病和胰岛素抵抗的一个强大风险因素。本研究证实,在传代培养的人前脂肪细胞中存在雄激素受体,具有雄激素受体基因表达和可饱和的特异性双氢睾酮结合,解离常数为1.02 - 2.56 nM,最大结合容量为30.8 - 55.7 fmol/mg蛋白质。雄激素受体补体存在内在的区域差异,内脏前脂肪细胞中的雄激素受体比皮下前脂肪细胞中的更多。双氢睾酮被人前脂肪细胞代谢,皮下前脂肪细胞产生的雄烷二醇比内脏前脂肪细胞更多。虽然双氢睾酮代谢不足以解释雄激素结合的区域差异,但与内脏前脂肪细胞相比,这两种差异都会降低皮下前脂肪细胞的雄激素反应性。雄激素结合或代谢不存在性别差异。虽然雄激素对人前脂肪细胞的直接作用仍不确定,但这些区域差异表明,AR介导的某些前脂肪细胞功能调节会影响脂肪组织分布。

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