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)


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.


Estrogen Receptor Estrogen Antagonist Slow Component Fast Component Kinetic Phasis 
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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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