Elevated serum bisphenol A levels under hyperandrogenic conditions may be caused by decreased UDP-glucuronosyltransferase activity
Elevated serum bisphenol A levels under hyperandrogenic conditions may be caused by decreased UDP-glucuronosyltransferase activity
复制标题
DOI：
10.1507/endocrj.k06-032
复制
发表时间：
2006-08-01
影响因子：
2
通讯作者：
Taketani, Yuji
中科院分区：
文献类型：
--
作者：
Takeuchi, Toru;Tsutsumi, Osamu;Taketani, Yuji
本研究旨在探讨雄激素对内分泌干扰物双酚A（BPA）代谢的影响，以阐明男性和高雄激素血症女性血清BPA水平高于正常女性的机制。去势雌性大鼠（OVX）皮下注射丙酸睾酮（TP）（0.01，0.1和1毫克），每天2周。OVX大鼠血清BPA浓度呈TP剂量依赖性增加，在0.1和1.0 mg TP时显著升高。大鼠肝微粒体中BPA葡萄糖醛酸化的酶反应显示，OVX大鼠中葡萄糖醛酸的比率以TP剂量依赖性方式显著降低。通过实时定量RT-PCR分析UDP-葡萄糖醛酸基转移酶2131（UGT 2B 1）的mRNA表达，结果显示UGT 2B 1 mRNA的相对表达水平呈TP剂量依赖性降低。酶分析结果表明，BPA葡萄糖醛酸化率和UGT 2B 1 mRNA的表达水平显着降低高雄激素条件下。BPA的清除可能以TP剂量依赖性方式减慢，导致高雄激素血症条件下血清BPA浓度增加。
This study was performed to investigate the effect of androgen on the metabolism of bisphenol A (BPA), an endocrine disruptor, in order to clarify the mechanism of the higher levels of serum BPA in men and hyperandrogenernic women compared with normal women. Castrated female rats (OVX) were subcutaneously injected with testosterone propionate (TP) (0.01, 0.1, and 1 mg) every day for 2 weeks. Serum BPA concentrations in OVX rats showed a TP dose-dependent increase and were significantly higher at 0.1 and 1.0 mg of TP. The enzyme reaction of BPA glucuronidation in the rat liver microsomes showed that the ratio of glucuronide in the OVX rats was significantly reduced in a TP dose-dependent manner. Analysis of the mRNA expression of UDP-glucuronosyltransferase 2131 (UGT2B1) by real-time quantitative RT-PCR revealed that the relative expression level of UGT2B1 mRNA showed a TP dose-dependent decrease. The results of enzyme analyses demonstrated that the ratio of BPA glucuronidation and the expression level of UGT2B1 mRNA were significantly lower under the hyperandrogenernic conditions. The clearance of BPA may be slowed in a TP dose-dependent manner, resulting in an increase of serum BPA concentration under hyperandrogenemic conditions.