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In-Vitro Determination of Biological and Anabolic Functions of Weak Androgen Dehydroepiandrosterone (DHEA) Using a Variety of Cell Lines

机译:使用多种细胞系体外测定弱雄激素脱氢表雄酮(DHEA)的生物学和合成代谢功能

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Dehydroepiandrosterone (DHEA) is a weak androgen and is shown to have anti-cancer, anti-atherogenic, anti-adipogenic and anti-inflammatory effects on mouse, rat and rabbit models. However, human clinical trials data did not support animal findings and were inconclusive. These systemic differences in biological actions between rodents and humans were attributed to the low level of DHEA in rodents. In order to further understand the differences in biological functions between rodents and humans, we resorted to an in-vitroapproach involving mouse, rat and human cell lines to assess DHEA biological and anabolic functions separately and independently without systemic influence. Results indicated that DHEA was effective on mouse and rat cell lines but not on human cell lines, as observed in in-vivo studies. In addition, our in-vitrostudy showed that DHEA was able to induce myogenesis in mouse mesenchymal cells revealing its anabolic function, even though DHEA was considered as a weak androgen. This observation lent credence to the ban on DHEA by IOC medical commission, citing DHEA as an anabolic steroid. These in-vitro experiments suggested that the differences in biological actions of DHEA between rodents and humans existed not only in-vivo at the systemic level, but also in-vitro at the cellular level and thus paving the way to study the mechanism responsible for these differences at the cellular level itself.
机译:脱氢表雄酮(DHEA)是一种弱雄激素,已显示对小鼠,大鼠和兔子模型具有抗癌,抗动脉粥样硬化,抗脂肪形成和抗炎作用。但是,人类临床试验数据不支持动物发现,也没有定论。啮齿动物和人类之间生物学行为的这些系统性差异归因于啮齿动物中DHEA含量低。为了进一步了解啮齿动物和人类之间生物学功能的差异,我们采用了一种涉及小鼠,大鼠和人类细胞系的体外方法,分别和独立地评估DHEA的生物学和合成代谢功能,而没有系统性影响。结果表明,体内研究表明,DHEA对小鼠和大鼠细胞系有效,但对人细胞无效。此外,我们的玻璃体内研究表明,即使DHEA被认为是一种弱雄激素,DHEA仍能够诱导小鼠间充质细胞的肌发生,从而揭示其合成代谢功能。该观察结果证明了国际奥委会医学委员会对脱氢表雄酮的禁令,理由是脱氢表雄酮是一种合成代谢类固醇。这些体外实验表明,啮齿动物和人类之间DHEA生物学活性的差异不仅存在于体内,而且还存在于细胞水平的体外,从而为研究引起这些现象的机制铺平了道路。细胞水平本身的差异。

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