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• W2040887597 abstract "The interaction of tamoxifen with the rat uterine oestrogen receptor protein has been investigated. The administration of tamoxifen to immature female rats produced a dose-dependent decrease in cytoplasmic oestrogen receptor concentrations and exchange methods were used to demonstrate a rise in nuclear oestrogen receptor concentrations. In immature rat uterine weight tests tamoxifen produced a partial uterotrophic response over a dose range of 0.5–8.0 μg/day and the same doses, administered simultaneously with oestradiol, produced a dose-related inhibition of oestrogen-stimulated uterine wet weight increases and uterine DNA content. Measurement of cytoplasmic oestrogen receptor concentrations during a uterine weight test demonstrated that 4 μg tamoxifen produced significant antiuterotrophic effects without a complete depletion of cytoplasmic oestrogen receptors. A single administration of tamoxifen (4 μg) produced a slow but prolonged rise in uterine wet weight associated with a slow decrease in cytoplasmic oestrogen receptors and a prolonged rise in oestrogen receptor levels in the nucleus. By 24 h cytoplasmic oestrogen receptor concentrations had returned to control levels. After a single dose of oestradiol (0.08 μg) there was a rapid decrease in cytoplasmic oestrogen receptors associated with a rapid rise in uterine wet weight but only a small rise in nuclear oestrogen receptor concentrations. In oestradiol-treated animals neither rises in uterine weight nor nuclear oestrogen receptor concentrations were maintained after 24 h. Oestrogen receptors which were translocated to the nucleus after a large dose of oestradiol (0.9 μg) were in the main salt (0.4 M KC1) extraetable although a small but significant proportion were salt resistant. By comparison oestrogen receptors translocated after tamoxifen were completely salt extractable. It is suggested that the change in the properties of the oestrogen receptor is responsible for the partial agonistic effects of tamoxifen. Since tamoxifen does not have to deny oestrogen binding completely to produce antioestrogenic effects in the uterus, a competition between tamoxifen-oestrogen receptor complexes and oestradiol-oestrogen receptor complexes for nuclear acceptor sites may be the primary antioestrogenic mechanism." @default.
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• W2040887597 date "1977-04-01" @default.
• W2040887597 modified "2023-09-25" @default.
• W2040887597 title "Studies on the mechanism of action of the nonsteroidal antioestrogen tamoxifen (I.C.I. 46,474) in the rat" @default.
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• W2040887597 doi "https://doi.org/10.1016/0303-7207(77)90066-1" @default.
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