Differential interaction of antiestrogens with cytosol estrogen receptors.
Interaction of tamoxifen, trioxifene and LY117018 with cytosol-estrogen receptors from immature rat uteri was compared. Determination of relative binding affinity (RBA) by competition with [3H] estradiol under various assay conditions revealed that the RBA of LY117018 increased with temperature while that of trioxifene declined. Furthermore, the RBA values of tamoxifen and trioxifene observed after 24 h of incubation at 4 degrees C were significantly lower than those obtained with 1-h incubations. However RBA values obtained with 1- or 24-h incubations of LY117018 at 4 degrees C were similar. The complex formed by estradiol or LY117018 at 4 degrees was relatively stable for 24 h, while significant dissociation of tamoxifen and trioxifene was detected under these conditions. At 30 degrees C estradiol displayed a biphasic pattern of dissociation, but tamoxifen and trioxifene dissociated rapidly and little evidence of a stable phase was apparent. By contrast, the complex formed by LY117018 exhibited greater stability than that of estradiol at 30 degrees C. These results establish a relationship between shifts in competition curves (RBA) and rates of dissociation relative to estradiol; and clearly reveal that LY117018 has different binding characteristics than tamoxifen and trioxifene.
D000818:Animals; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000378:metabolism*; D005260:Female; D011759:Pyrrolidines / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000378:metabolism; D013696:Temperature; D013876:Thiophenes / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D004965:Estrogen Antagonists; D011759:Pyrrolidines; D011960:Receptors, Estrogen; D013876:Thiophenes; D013629:Tamoxifen; D004958:Estradiol; C025430:LY 117018; C014934:trioxifene