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- W2055393621 abstract "Abstract Androgens are natural estrogen antagonists currently used in the treatment of breast cancer. We have compared the initial steps of action of androgens and of synthetic antiestrogens in the rat and calf uterus and in the 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary tumors. (a) Synthetic antiestrogens bind “competitively” to the cytosol estrogen receptor (ER) and induce in vivo its nuclear translocation and replenishment. We now show that [3H]-dimethylstilboestrol and [3H]-tamoxifen interact directly with the 8S ER, with a much higher affinity than that calculated from competitive experiments. The antiestrogens differed from estradiol by a rapid dissociation rate and a lack of protection of ER binding sites against heat inactivation. 1. (b) Androgens at high concentration bind in vitro stereospecifically to ER. [ 3 H ]-5α- androstane -3β,17β- diol , and [ 3 H ]-5 ene-androstene -3β,17β- diol interact directly with the 8S ER. This binding induces the nuclear translocation of the ER as initially observed in rat uteri and DMBA mammary tumors. In vivo. dihydrotestosterone increased the incorporation of [3H]-leucine into protein and was efficient in inducing the progesterone receptor and proteins similar to the E2-induced protein. The similarity between the in vitro interaction of androgens and synthetic antiestrogens to ER suggest a similar mechanism of action, even though marked differences at the nuclear “acceptor level” are not excluded." @default.
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- W2055393621 date "1979-11-01" @default.
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- W2055393621 title "Mechanism of action of antiestrogens and androgens on the estrogen receptor" @default.
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- W2055393621 doi "https://doi.org/10.1016/0022-4731(79)90361-3" @default.
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