Evidence for biological action of the antiestrogens LY117018 and tamoxifen by different mechanisms.
The influence of LY117018 and tamoxifen on established uterotropic influence of estradiol was examined in immature ovariectomized rats. When LY117018 was introduced on the fourth day of estradiol treatment, it regressed the uterotropic effect of estradiol. However, tamoxifen did not attenuate estradiol activity under these conditions. Injection of estradiol, commencing on the fourth day of LY117018 treatment, elicited no increase in uterine weight, while tamoxifen caused substantial uterotropic action in the presence of established, continuous LY117018 treatment. The uterotropic influence of tamoxifen also occurred when it was administered concomitantly with LY117018, and a similar result was observed following the injection of 4-hydroxytamoxifen with LY117018. These observations demonstrate that LY117018 can block or regress uterotropic effects of estradiol, but it cannot antagonize the action of tamoxifen or its hydroxylated metabolite. This suggests that these antiestrogens might act at separate sites or by different molecular mechanisms.
D000818:Animals; D002369:Castration; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen / Q000378:metabolism; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
D004965:Estrogen Antagonists; D011759:Pyrrolidines; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D013876:Thiophenes; D013629:Tamoxifen; D004958:Estradiol; C025430:LY 117018