Investigation of testosterone, androstenone, and estradiol metabolism in HepG2 cells and primary culture pig hepatocytes and their effects on 17βHSD7 gene expression.
Investigation of testosterone, androstenone, and estradiol metabolism in HepG2 cells and primary culture pig hepatocytes and their effects on 17βHSD7 gene expression.
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DOI：
10.1371/journal.pone.0052255
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Doran O
中科院分区：
文献类型：
--
作者：
Chen G;Li S;Dong X;Bai Y;Chen A;Yang S;Fang M;Zamaratskaia G;Doran O
类固醇代谢在许多物种中很重要。雄激素代谢产物雄烯酮在猪脂肪组织中的积累与猪肉的风味、气味呈负相关，使猪肉不适合人类食用。17β-羟基类固醇脱氢酶7（17β-hydroxysteroid dehydrogenase type 7，17β HSD 7）在猪肝脏中大量表达，并与雄甾烯酮水平相关。了解酶和代谢途径负责雄甾烯酮以及其他类固醇代谢是重要的改善肉质。同时，已知类固醇的代谢具有种属特异性和组织特异性。因此，研究肝脏类固醇代谢的种间差异并阐明17β HSD 7在该过程中的作用是重要的。在这里，我们使用了一种有效的方法学手段，液相色谱-质谱联用，研究种特异性代谢的雄甾烯酮，睾酮和β-雌二醇在HepG 2细胞系，和猪培养的肝细胞。还研究了类固醇对17β HSD 7基因表达的种属和浓度依赖性效应。结果表明，甾体激素对HepG 2和原代培养猪肝细胞17β HSD 7基因表达具有浓度依赖性和种属依赖性调节作用。甾体代谢产物研究表明，雄甾烯酮形成3′-羟基化合物3β-羟基-5 α-雄甾-16-烯。睾酮代谢为4-雄甾烯-3，17-二酮。发现雌酮是β-雌二醇的代谢产物。17βHSD抑制剂芹菜素对雄甾烯酮代谢的抑制作用表明，芹菜素不影响雄甾烯酮的代谢。高浓度（50 µM）芹菜素倾向于抑制睾酮代谢，但这种抑制作用可以忽略不计。芹菜素在高浓度时显著抑制β-雌二醇代谢。该研究还确定，与高浓度芹菜素共孵育后，睾酮和β-雌二醇代谢产物的水平显著增加。本研究证实，17β HSD 7不是猪肝细胞中负责雄烯酮和睾酮代谢的关键酶。
Steroid metabolism is important in various species. The accumulation of androgen metabolite, androstenone, in pig adipose tissue is negatively associated with pork flavor, odour and makes the meat unfit for human consumption. The 17β-hydroxysteroid dehydrogenase type 7 (17βHSD7) expressed abundantly in porcine liver, and it was previously suggested to be associated with androstenone levels. Understanding the enzymes and metabolic pathways responsible for androstenone as well as other steroids metabolism is important for improving the meat quality. At the same time, metabolism of steroids is known to be species- and tissue-specific. Therefore it is important to investigate between-species variations in the hepatic steroid metabolism and to elucidate the role of 17βHSD7 in this process. Here we used an effective methodological approach, liquid chromatography coupled with mass spectrometry, to investigate species-specific metabolism of androstenone, testosterone and beta-estradiol in HepG2 cell line, and pig cultured hepatocytes. Species- and concentration-depended effect of steroids on 17βHSD7 gene expression was also investigated. It was demonstrated that the investigated steroids can regulate the 17βHSD7 gene expression in HepG2 and primary cultured porcine hepatocytes in a concentration-dependent and species-dependent pattern. Investigation of steroid metabolites demonstrated that androstenone formed a 3′-hydroxy compound 3β-hydroxy-5α-androst-16-ene. Testosterone was metabolized to 4-androstene-3,17-dione. Estrone was found as the metabolite for β-estradiol. Inhibition study with 17βHSD inhibitor apigenin showed that apigenin didn’t affect androstenone metabolism. Apigenin at high concentration (50 µM) tends to inhibit testosterone metabolism but this inhibition effect was negligible. Beta-estradiol metabolism was notably inhibited with apigenin at high concentration. The study also established that the level of testosterone and β-estradiol metabolites was markedly increased after co-incubation with high concentration of apigenin. This study established that 17βHSD7 is not the key enzyme responsible for androstenone and testosterone metabolism in porcine liver cells.
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猪3β-羟基类固醇脱氢酶和17β-羟基类固醇脱氢酶基因转录因子的调查。
影响因子：
3.5
作者：
Dong, Xinxing;Bai, Ying;Fang, Meiying
通讯作者：
Fang, Meiying
影响因子：
5.1
作者：
Doran, E;Whittington, FA;McGivan, JD
通讯作者：
McGivan, JD
影响因子：
4.1
作者：
PATTERSON, RL
通讯作者：
PATTERSON, RL
影响因子：
2.7
作者：
Rauh, Manfred;Groeschl, Michael;Doerr, Helmuth G.
通讯作者：
Doerr, Helmuth G.
影响因子：
3.3
作者：
Chen, G.;Bourneuf, E.;Lundstrom, K.
通讯作者：
Lundstrom, K.