The Role of Ligand-Binding as a Determinant of the Structure and Activation of the Estrogen Receptor

  • A. C. Notides
  • B. M. Weichman
  • N. Lerner
  • W. de Boer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 117)

Summary

The dissociation of estradiol from the estrogen receptor occurs in two kinetic phases: a fast component having a half-time of approximately 3 min and a slower, or second, dissociating component having a half-time of approximately 95 min at 28°. The fast component is produced by the dissociation of estradiol from the nonactivated 4 S receptor, a monomer. Thus, the magnitude of the fast component of the [3H] estradiol biphasic dissociation curve is proportional to the fraction of the receptor in the non-activated state. The slow component is the estradiol dissociating from the activated 5 S receptor, a dimer. The salt-extracted estrogen receptor isolated from uterine nuclei shows a single, slow dissociating component equal to the slower component of the cytoplasmic biphasic dissociation curve. Estradiol binding shifts the receptor equilibrium from the low affinity nonactivated 4 S receptor toward the high affinity activated 5 S receptor. The kinetics of estriol dissociation from the receptor shows a larger fractional magnitude for the fast component and a faster second dissociating component than estradiol. This suggests that estriol transforms a smaller fraction of the receptor to the activated state and that the activated estriol receptor has a shorter halftime than estradiol. The biphasic dissociation kinetics of an estrogen from the receptor provides a new and sensitive criterion for measuring receptor activation.

Keywords

Estrogen Receptor Estrogen Antagonist Slow Component Fast Component Kinetic Phasis 
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

© Springer Science+Business Media New York 1979

Authors and Affiliations

  • A. C. Notides
    • 1
  • B. M. Weichman
    • 1
  • N. Lerner
    • 1
  • W. de Boer
    • 1
  1. 1.Department of Pharmacology and ToxicologyUniversity of RochesterRochesterUSA

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