Estrogen- and antiestrogen-induced ornithine decarboxylase activity and uterine growth in the rat.
The estrogen antagonists tamoxifen and monohydroxytamoxifen are also classified as partial estrogen agonists. In infantile rats, estradiol induced a single peak of uterine ODC activity at 6h following injection regardless of the extent of induction by various estradiol doses. By contrast, the timing of the ODC activity peak induced by tamoxifen and monohydroxytamoxifen was highly dependent upon the dosing conditions and was delayed to 18 h at lower tamoxifen doses. In immature rats, tamoxifen and monohydroxytamoxifen induced two peaks of uterine ODC activity resembling those induced by estradiol. Both ODC activity peaks were delayed by 9 h, without decreases in peak heights, by a 50-fold tamoxifen dose reduction. In all experiments the initial appearance of antiestrogen- and estradiol-induced ODC activity corresponded to initial uterine wet weight gain regardless of dosing condition. Thus, when dose-related temporal shifts are taken into account, tamoxifen and monohydroxytamoxifen are complete agonists with respect to induction of uterine weight gain and ODC activity.
Branham
W S
WS
Department of Health and Human Services, National Center for Toxicological Research, Jefferson, AR 72079.
Leamons
M L
ML
Sheehan
D M
DM
D000818:Animals; D004790:Enzyme Induction; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014599:Uterus / Q000033:anatomy & histology* / Q000187:drug effects / Q000201:enzymology
D004965:Estrogen Antagonists; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; D009955:Ornithine Decarboxylase