Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver

Bisphenol A, an environmental oestrogenic chemical, was found to conjugate highly with glucuronic acid in male rat liver microsomes studied in vitro. In the various isoforms tested (1A1, 1A3, 1A5, 1A6, 1A7 and 2B1), glucuroni dation of bisphenol A and of diethylstilboestrol, a synthetic crystalline c ompound possessing oestrogenic activity and known to be glucuronidated by l iver microsomes, was catalysed by an isoform of UDP-glucuronosyltransferase (UGT), namely UGT2BI, which glucuronidates some endogenous androgens. UGT activity towards bisphenol A in liver microsomes and in UGT2B1 expressed in yeast AH22 cells (22.9 and 0.58 nmol/min per mg of microsomal proteins res pectively) was higher than that towards diethylstilbuestrol (75.0 and 4.66 pmol/min per mg of micro-somal proteins respectively). UGT activities towar ds both bisphenol A and diethylstilboestrol were distributed mainly in the liver but were also observed at substantial levels in the kidney and testis . Northern blot analysis disclosed the presence of UGT2B1 solely in the liv er, and about 65% of the male rat liver microsomal UGT activities towards b isphenol A were absorbed by the anti-UGT2B1 antibody. These results indicat e that bisphenol A, in male rat liver, is glucuronidated by UGT2B1, an isof orm of UGT.