Interaction of estrogen mimics, singly and in combination, with plasma sex steroid-binding proteins in rainbow trout (Oncorhynchus mykiss).
The plasma sex steroid-binding protein (SBP) is believed to be involved in regulating circulating endogenous sex steroids as well as cellular signal transduction to nuclear steroid receptors in sex steroid-sensitive tissues. In this study, a variety of estrogen mimics (EMs), which may contribute to the endocrine disrupting effects observed in fish, were tested for the ability to interact with the rainbow trout plasma sex steroid-binding protein (rtSBP) either singly or in binary combinations. The EMs ethynylestradiol, diethylstilbestrol, 4-hydroxytamoxifen, genistein, zearalenone, 4-t-octylphenol, bisphenol A and o,p'-DDT were all able to displace 1,2,4,6,7-[3H]estradiol from the sex steroid-binding site at the rtSBP (K(d)=2.1+/-0.5 nM, B(max)=2963+/-303 fmol estradiol/mg protein) in a dose-dependent and competitive manner. The plastizicer n-butyl benzyl phthalate only displayed weak binding affinity for the rtSBP, whereas the pesticide dieldrin was not able to compete for the high affinity estradiol-binding sites in plasma. None of the compounds tested was able to clearly promote the binding of the others when given in combination, indicating that synergy did not occur at the ligand-SBP binding level. The rtSBP binding affinity for EMs ranged over several orders of magnitude, but were consistently lower than those for the endogenous sex steroids (about 10(2)-10(6) less potent). The results suggest that the presence of rtSBP may potentially modulate the bioavailability of EMs to estrogen receptors relative to each other and to the endogenous sex steroids themselves. Since the binding of the endogenous ligands is reversible, SBP-bound estrogens (or androgens) potentially may also become displaced by potent EMs.
Tollefsen
K-E
KE
Toxicology Laboratory, Division of Molecular Cell Biology, Department of Biology, University of Oslo, PO Box 1050 Blindern, N-0316, Oslo, Norway. knut-erik.tollefsen@biosense.no
D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D045166:Estradiol Congeners / Q000097:blood / Q000378:metabolism*; D004967:Estrogens / Q000097:blood / Q000378:metabolism*; D005260:Female; D008297:Male; D017686:Oncorhynchus mykiss / Q000097:blood*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D015398:Signal Transduction
D045166:Estradiol Congeners; D004967:Estrogens; D012738:Sex Hormone-Binding Globulin