Elevated serum bisphenol A levels under hyperandrogenic conditions may be caused by decreased UDP-glucuronosyltransferase activity.
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 hyperandrogenemic 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 2B1 (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 hyperandrogenemic 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.
Takeuchi
Toru
T
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan.
Tsutsumi
Osamu
O
Ikezuki
Yumiko
Y
Kamei
Yoshimasa
Y
Osuga
Yutaka
Y
Fujiwara
Toshihiro
T
Takai
Yasushi
Y
Momoeda
Mikio
M
Yano
Tetsu
T
Taketani
Yuji
Y
D000818:Animals; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors / Q000097:blood* / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D010052:Ovariectomy; D010636:Phenols / Q000097:blood*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D014453:Glucuronosyltransferase; D010636:Phenols; D012333:RNA, Messenger; D013739:Testosterone; C006780:bisphenol A; D000098826:Bisphenol A Compounds