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Tamoxifen is a potent ‘pure’ anti-oestrogen in chick oviduct

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Abstract

OESTROGEN responsive cells contain a specific proteinaceous macromolecule—one receptor—capable of recognising physiologically active oestrogens as well as a number of synthetic oestrogen agonists and antagonists1,2. In the nonstimulated state, the majority of receptors are located in the cytoplasmic fraction of responsive cells3,4, including the chick oviduct5. When oestrogen reaches the target cell, it binds to the cytoplasmic receptor causing its ‘activation’ and the translocation of the hormone–receptor complex to the nucleus. The interaction of receptor with chromatin is thought to facilitate gene transcription and the synthesis of proteins implicated in the changes characteristic of the oestrogenic response6,7. Receptor is retained in the nucleus for varying periods of time depending on the concentration and nature of the oestrogen. In the rat uterus, the length of time that receptor is retained in the nucleus correlates well with a number of parameters of the hormonal response8. The initial translocation of receptor to the nucleus is followed by a period of cytoplasmic receptor replenishment3–5,9. This process is very important as it has been implicated in the ability of cells to respond to subsequent oestrogenic stimulation10,11. Anti-oestrogens prevent oestrogens from expressing their full effects on oestrogen target tissues. Recent studies have indicated that some non-steroidal anti-oestrogens (CI-628, nafoxidine and clomiphene) bind to cytoplasmic oestrogen receptor, induce the translocation of the antagonist–receptor complex to the nucleus, but fail to stimulate subsequent cytoplasmic receptor replenishment12–14. Oestrogen antagonism would be primarily due to inhibition of cytoplasmic receptor replenishment12. Further, such a hypothesis could explain the weak oestrogenic activity of these compounds following a single injection when cytoplasmic receptor is translocated to the nucleus, and their subsequent potent anti-oestrogenic activity after serial injections when the low cytoplasmic receptor level is the limiting factor in receptor translocation15. We present here results which illustrate that this theory of anti-oestrogenic action does not hold for tamoxifen (ICI 46,474) in the chicken oviduct.

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Authors and Affiliations

  1. Lab Hormones-U 33 Inserm, 94270, Bicêtre, France

    ROB SUTHERLAND, JÁN MEŠTER & ETIENNE-EMILE BAULIEU

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  1. ROB SUTHERLAND
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  2. JÁN MEŠTER
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  3. ETIENNE-EMILE BAULIEU
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SUTHERLAND, R., MEŠTER, J. & BAULIEU, EE. Tamoxifen is a potent ‘pure’ anti-oestrogen in chick oviduct. Nature 267, 434–435 (1977). https://doi.org/10.1038/267434a0

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