Androgen-mediated down-regulation of CYP1A subfamily genes in the pig liver
Androgen-mediated down-regulation of CYP1A subfamily genes in the pig liver
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DOI：
10.1677/joe-10-0160
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发表时间：
2010-11-01
影响因子：
4
通讯作者：
Degawa, Masakuni
中科院分区：
文献类型：
--
作者：
Kojima, Misaki;Sekimoto, Masashi;Degawa, Masakuni
研究了梅山猪和长白猪肝细胞色素P4501A （CYP1A）亚家族酶组成表达的mRNA、蛋白和酶活性的性别差异。实时RT-PCR、western blotting和CYP1A亚家族酶的酶分析结果表明，5月龄梅山猪雄性CYP1A1和CYP1A2的表达水平显著低于雌性。相比之下，长白猪没有这种显著的性别差异。雄性梅山猪阉割导致CYP1A亚家族酶的雌性型表达，而雄性长白猪阉割后没有观察到这种影响。在这两个品种的猪中，雌性和阉割的雄性给药丙酸睾酮导致CYP1A亚家族酶的mrna和蛋白质表达水平显著降低，酶活性也显著降低。此外，对不同性成熟（1-5月龄）雄性猪血清睾酮水平与CYP1A亚家族酶基因表达水平的相关性分析表明，当血清睾酮浓度超过33 ng/ml时，肝脏CYP1A亚家族酶的表达水平明显下降。同时，5月龄长白猪和梅山猪的血清睾酮平均浓度分别约为18和50 ng/ml。综上所述，我们首次证明血清睾酮水平是调节猪肝脏CYP1A1和CYP1A2组成性表达的生理因素之一。内分泌学杂志（2010）207,203-211
In Meishan and Landrace pigs, sex differences in the constitutive expression of hepatic cytochrome P4501A (CYP1A) subfamily enzymes were examined in terms of their mRNA, protein, and enzyme activity. All the results from the real-time RT-PCR, western blotting, and enzyme assays for CYP1A subfamily enzymes indicated that, in 5-month-old Meishan pigs, the expression levels of CYP1A1 and CYP1A2 in males were significantly low as compared with those in females. In contrast, there were no such significant sex differences in Landrace pigs. Castration of male Meishan pigs led to a female-type expression of the CYP1A subfamily enzymes, whereas no such effect was observed in male Landrace pigs after castration. In both breeds of pigs, the administration of testosterone propionate to the females and castrated males led to marked decreases in the expression levels of mRNAs and proteins in the CYP1A subfamily enzymes, and also in their enzyme activities. Furthermore, the correlation analyses between the serum testosterone level and the gene expression levels of CYP1A subfamily enzymes in different sex-matured (1-5-month-old) male pigs revealed that the clear decrease in expression levels of hepatic CYP1A subfamily enzymes occurred at concentrations of more than 33 ng/ml of serum testosterone. Incidentally, the mean concentrations of serum testosterone in 5-month-old Landrace and Meishan pigs were around 18 and 50 ng/ml respectively. In conclusion, we demonstrated for the first time that the serum testosterone level is one of the physiological factors which regulate constitutive expression of hepatic CYP1A1 and CYP1A2 in pigs. Journal of Endocrinology (2010) 207, 203-211