Competitive binding of xenobiotic oestrogens to rat alpha-fetoprotein and to sex steroid binding proteins in human and rainbow trout (Oncorhynchus mykiss) plasma.
The ability of a variety of "environmental oestrogens" to compete with radiolabelled steroids to rat alpha-fetoprotein (AFP) and to sex steroid binding proteins was investigated in human and rainbow trout (Oncorhynchus mykiss) plasma. For [3H]oestradiol binding to AFP, diethylstilbestrol and 4-nonylphenoxyacetic acid showed significant competition at concentrations about 100-fold greater than oestradiol (relative binding affinities approximately 1% c.f. oestradiol). All other compounds (phytooestrogens: coumestrol, daidzein, genistein; others: 4-nonylphenol, 4-tert-octylphenol, 4-nonylphenoldiethoxylate, 4-tert-butylphenol, bisphenol-A (Bis-A), bis(2- ethylhexl)phthalate, dioctylphthalate, dibutyl phthalate, 2, 4'DDT (op' enantiomer), 2,4'-DDE (mixed enantiomers), kepone) showed only very weak or no competition (relative binding affinities <<0.1% c.f. oestradiol). The situation for both human and fish plasma was very similar, with only very high concentrations (>>1000 fold more than the natural ligand) of a few of the compounds showing any ability to displace the natural ligand. These results suggest that environmental oestrogenic agents are unlikely to produce biological effects by displacing endogenous steroids from plasma steroid binding proteins unless they are present in very high concentrations.
Milligan
S R
SR
Physiology Group, Biomedical Sciences Division, King's College London, Strand, London, WC2R 2LS, United Kingdom. Stuart.Milligan@kcl.ac.uk
Khan
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O
Nash
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M
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000097:blood*; D013196:Dihydrotestosterone / Q000097:blood; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D017686:Oncorhynchus mykiss / Q000097:blood*; D011247:Pregnancy; D051381:Rats; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D015262:Xenobiotics / Q000097:blood*; D000509:alpha-Fetoproteins / Q000378:metabolism*
D002352:Carrier Proteins; D012738:Sex Hormone-Binding Globulin; D015262:Xenobiotics; D000509:alpha-Fetoproteins; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol