Sulfonation of environmental estrogens by zebrafish cytosolic sulfotransferases.
Environmental estrogen-like chemicals are increasingly recognized as a potential hazardous factor for wildlife as well as humans. We have recently embarked on developing a zebrafish model for investigating the role of sulfonation in the metabolism and adverse functioning of environmental estrogens. Here, we report on a systematic investigation of the sulfonation of representative environmental estrogens (bisphenol A, 4-n-octylphenol, 4-n-nolylphenol, diethylstilbestrol, and 17 alpha-ethynylestradiol) by zebrafish cytosolic sulfotransferases (STs). Of the seven enzymes tested, four zebrafish STs (designated ZF ST #2, ZF ST #3, ZF ST #4, and ZF DHEA ST) exhibited differential sulfonating activities toward the five environmental estrogens tested, with ZF ST #3 being more highly active than the other three. It was further demonstrated that bisphenol A, 4-n-octylphenol, and 4-n-nonylphenol exerted concentration-dependent inhibition of the sulfonation of 17 beta-estradiol, implying a potential role of these environmental estrogens in interfering with the sulfonation, and possibly homeostasis, of endogenous estrogens. Kinetic studies revealed that the mechanism underlying the inhibition by bisphenol A or 4-n-nonylphenol to be of the competitive type.
Ohkimoto
Kei
K
Biomedical Research Center, The University of Texas Health Center, Tyler, TX 75708, USA.
Sugahara
Takuya
T
Sakakibara
Yoichi
Y
Suiko
Masahito
M
Liu
Ming-Yih
MY
Carter
Glendora
G
Liu
Ming-Cheh
MC
D000818:Animals; D001559:Benzhydryl Compounds; D003600:Cytosol / Q000201:enzymology* / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004054:Diethylstilbestrol / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004777:Environment; D045166:Estradiol Congeners / Q000737:chemistry; D004967:Estrogens / Q000378:metabolism*; D004968:Estrogens, Non-Steroidal / Q000737:chemistry; D004997:Ethinyl Estradiol / Q000737:chemistry; D007700:Kinetics; D010636:Phenols / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D020033:Protein Isoforms; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015238:Sulfotransferases / Q000737:chemistry*; D015027:Zebrafish; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D018076:DNA, Complementary; D004054:Diethylstilbestrol; D045166:Estradiol Congeners; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D004997:Ethinyl Estradiol; D010636:Phenols; D020033:Protein Isoforms; D011994:Recombinant Proteins; D015238:Sulfotransferases; C080417:4-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds