Inhibition of human and rat 11β-hydroxysteroid dehydrogenases activities by bisphenol A.
Bisphenol A (BPA) is a potential endocrine disruptor. It has been shown that it can interfere with steroid biosynthesis and metabolism. However, the mechanism is unclear. The objective of the present study is to investigate the effects of BPA on two isoforms of 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 11β-HSD2) in human and rat tissues. Human liver, rat testis microsomes as well as rat adult Leydig cells were used for measurement of 11β-HSD1 activity, and human and rat kidney microsomes for 11β-HSD2 activity. BPA inhibited human and rat 11β-HSD1 activities with the half maximal inhibitory concentrations (IC50s) of 14.81 ± 0.06 μM (mean ± SEM) for human and 19.39 ± 0.09 μM for rat enzyme, respectively. BPA inhibited rat 11β-HSD1 activity in intact rat Leydig cells. BPA also weakly inhibited both human and rat 11β-HSD2 activities. At 100 μM, BPA inhibited human and rat enzymes by 51.16% and 41.61%, respectively. In conclusion, BPA is an inhibitor for both 11β-HSD1 and 11β-HSD2, with selectivity against the type I enzyme.
The 2nd Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325000, PR China.
Jingjing
J
Guo
Xiaohuan
X
Yuan
Li
L
Qiu
Weiliu
W
Zhu
Chaonan
C
Wang
Guoxin
G
Hu
Yanhui
Y
Chu
Leping
L
Ye
Yunfei
Y
Xu
Ren-Shan
RS
Ge
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000098826:Bisphenol A Compounds
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds