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Metabolism of androstenone, 17β-estradiol and dihydrotestosterone in primary cultured pig hepatocytes and the role of 3β-hydroxysteroid dehydrogenase in this process

机译:猪原代培养的肝细胞中雄烯酮,17β-雌二醇和二氢睾丸酮的代谢及3β-羟类固醇脱氢酶的作用

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摘要

Steroids metabolism plays an important role in mammals and contributes to quality of pig meat. The main objective of this study was to identify metabolites of androstenone, 17b-estradiol and dihydrotestosterone using primary cultured pig hepatocytes as a model system. The role of 3b-hydroxysteroid dehydrogenase (3bHSD) in regulation of steroid metabolism was also validated using trilostane, a specific 3bHSD inhibitor. Steroid glucuronide conjugated metabolites were detected by liquid chromatography time of flight mass spectrometry (LC-TOF-MS). 3bHSD enzyme was essential for metabolism of androstenone to 5a-androst-16-en-3b-ol, which then formed androstenone glucuronide conjugate. Metabolism of 17bestradiol was accompanied by formation of glucuronide conjugated estrone and glucuronide-conjugated estradiol. The ratio of the two metabolites was around 5:1. 3bHSD enzyme was not involved in 17b-estradiol metabolism. 5a-Dihydrotestosterone-17b-glucuronide was identified as a dihydrotestosterone metabolite, and this metabolism was related to 3bHSD enzyme activity as demonstrated by inhibition study.
机译:类固醇的代谢在哺乳动物中起重要作用,并有助于提高猪肉的品质。这项研究的主要目的是使用原代培养的猪肝细胞作为模型系统来鉴定雄烯酮,17b-雌二醇和二氢睾酮的代谢产物。还使用特定的3bHSD抑制剂trilostane验证了3b-羟基类固醇脱氢酶(3bHSD)在类固醇代谢调节中的作用。通过液相色谱飞行时间质谱(LC-TOF-MS)检测类固醇葡糖醛酸苷共轭的代谢物。 3bHSD酶对于雄烯酮代谢为5a-androst-16-en-3b-ol必不可少,然后形成雄烯酮葡糖醛酸苷共轭物。 17bestradiol的代谢伴随着葡糖苷酸结合的雌酮和葡糖苷酸结合的雌二醇的形成。两种代谢物的比例约为5:1。 3bHSD酶不参与17b-雌二醇代谢。 5a-Dihydrotestosterone-17b-lucuronide被鉴定为二氢睾丸激素的代谢产物,这种代谢与3bHSD酶活性有关,如抑制研究所示。

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