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Antisteroid Hormones, Receptor Structure and Heat-Shock Protein MW 90,000 (HSP 90)

  • Etienne-Emile Baulieu
Part of the Serono Symposia, USA book series (SERONOSYMP)

Summary

Antisteroid hormones compete for hormone binding at the receptor level and prevent the hormonal response. A new parameter is proposed for explaining both antiglucocorticosteroid and antiprogesterone activities of RU 486, a synthetic derivative of high affinity for receptors. It is based on the antagonist ability to stabilize the hetero-oligomeric 8S-form of the glucocorticosteroid (in the chick oviduct) and progesterone (in the rabbit uterus) receptors. These 8-S complexes involve the interaction of the ~94,000 and ~120,000 Da receptor with the heat-shock protein of MW ~90,000 (hsp 90). It is proposed that hsp 90 caps the DNA binding site of the receptor, preventing it from interaction with the DNA of hormone regulatory elements (HRE) and thus from modifying transcription of regulated genes. In contrast, hormone agonists induce the dissociation of the hetero-oligomeric form of receptors, thus unmasking their functional DNA binding domain. Whether other differences between agonist- and antagonist-receptor complexes are involved in the expression of hormone and antihormone effects also is discussed in this paper.

Keywords

Glucocorticoid Receptor Triamcinolone Acetonide Mouse Mammary Tumor Virus Triamcinolone Acetonide Hormone Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Etienne-Emile Baulieu
    • 1
  1. 1.INSERM U 33 and Faculte de Medecine Paris-Sud Lab HormonesBicetre CedexFrance

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