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

给予双酚 A 的成年雄性大鼠中 UDP-葡萄糖醛酸基转移酶对性激素的活性

• 批准号: 13833008
• 负责人: YOKOTA Hiroshi
• 金额: $ 2.37万
• 依托单位: Rakuno Gakuen University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13833008/
• 关键词: UDP-glucumnosyltransferase; Glucuronidation; Hormone; Bisphenol A; Estradiol; Xenoestrogen; グルクロン酸抱合反応; グルクロン酸抱合; 内分泌攪乱化学物質; UDP-glucuronosyltransferase; UGT2B1; エストラジオール; エストロジェン受容体

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.

内分泌干扰物对雄性动物生殖器官的各种不良影响已被报道。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。

项目成果

Inoue, H., Yuki, G., Yokota, H., Kato S.: "Bisphenol A Glucuronidation and Absorption in Rat Intestine"Drug Metab.Dispos.. 31. 140-144 (2003)

Inoue, H.、Yuki, G.、Yokota, H.、Kato S.：“大鼠肠道中的双酚 A 葡萄糖醛酸化和吸收”Drug Metab.Dispos.. 31. 140-144 (2003)

Yamashiki, N.: "Presence of Phenol UDP-glucuronosyltransferase in Bovine Alveolar Macrophages and Bronchial Epithelial Cells"Toxicology. 176(3). 221-227 (2002)

Yamashiki, N.：“牛肺泡巨噬细胞和支气管上皮细胞中苯酚 UDP-葡萄糖醛酸基转移酶的存在”毒理学。

Yokota, H., Kunimasa, Y., Shimoyama, Y., Kobayashi, T., Matsumoto, J., Yuasa, A: "Tissue Specific Effects on UDP-glucuronosyltransferase in Hypophysectomized Rat"J.Biochem. 132. 265-270 (2002)

Yokota, H.、Kunimasa, Y.、Shimoyama, Y.、Kobayashi, T.、Matsumoto, J.、Yuasa, A：“对垂体切除大鼠中 UDP-葡萄糖醛酸基转移酶的组织特异性影响”J.Biochem。

Matsumoto, J., Yokota, H., Yuasa, A.: "Developmental Increase in Rat Hepatic Microsomal UDP-glucuronosyltransferase activities toward Xenoestrogens and Decrease during Pregnancy"Environ Health Perspect. 110(2). 193-196 (2002)

Matsumoto, J.、Yokota, H.、Yuasa, A.：“大鼠肝微粒体 UDP-葡萄糖醛酸基转移酶对异雌激素活性的发育增加和妊娠期间的减少”环境健康观点。

Inoue, H., Yuki, G., Yokota, H., Kato S.: "Bisphenol A Glucuronidation and Absorption in Rat Intestine"Drug Metab.Dispos. 31. 140-144 (2003)

Inoue, H.、Yuki, G.、Yokota, H.、Kato S.：“大鼠肠道中的双酚 A 葡萄糖醛酸化和吸收”药物代谢处​​置。