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

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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.