UDP-glucuronosyltransferase Activities toward Sex Hormones in the Adult Male Rat Administered Bisphenol A

据报道，内分泌干扰物对雄性动物生殖器官有各种不良影响。我们发现，UDP-葡萄糖醛酸基转移酶活性对双酚A，睾酮和雌二醇显着减少，从成年雄性Wistar大鼠的内分泌干扰物双酚A（1毫克/2天，2或4周）制备的肝微粒体。然而，即使在双酚A治疗4周后，在雌性大鼠中也未观察到转移酶活性的抑制。己烯雌酚，这是众所周知的内分泌干扰物，有同样的效果，但对枯基苯酚对UDP-葡萄糖醛酸转移酶活性对性激素没有影响。与抗雌激素药他莫昔芬共同给药可抑制双酚A对转移酶活性的抑制。Western blotting分析表明，UGT 2B 1，即葡萄糖醛酸双酚A，在大鼠肝微粒体中的含量减少的处理。北方印迹分析也表明双酚A处理降低了肝脏中UGT 2B 1 mRNA的表达。结果表明，双酚A处理降低了成年雄性大鼠UGT 2B 1和其它UGT亚型的mRNA表达，提示可能通过抑制性激素的葡萄糖醛酸化而破坏内分泌平衡。

Various adverse effects of endocrine disruptors on the reproductive organs of male animals have been reported. We found that UDP-glucuronosyltransferase activines towards bisphenol A, testosterone and estradiol were significantly decreased in liver microsomes prepared from adult male Wistar rats administered the endocrine disruptor bisphenol A (1 mg/2 days for 2 or 4 weeks). However, suppression of the transferase activities was not observed in female rats even after bisphenol A-treatment for 4 weeks. Diethylstilbestrol, which is well known as an endocrine disruptor, had the same effects, but p-cumylphenol had no effect on UDP-glucuronosyltransferase activities towards sex hormones. Co-administration with an antiestrogen, tamoxifen, inhibited the suppression of the transferase activities by bisphenol A. Western blotting analysis showed that the content of UGT2B1, which glucuronidates bisphend A, was decreased in the rat liver microsomes by the treatment. Northern blotting analysis also indicated that UGT2B1 mRNA in the liver was decreased by bisphenol A treatment. These suppressions of UDP-glucuronosyltmnsferase activities, UGT2B 1 protein and UGT2I3 1 mRNA expression did not occur in female rats.The results indicate that bisphenol A treatment reduces the mRNA expression of UGT2B 1 and other UGT isoforms mediating glucuronidation of sex hormones in adult male rats, and this suggests that endocrine balance may be disrupted by suppression of glucuronidation.