The role of ligand-binding as a determinant of the structure and activation of the estrogen receptor.
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 degrees. 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 nonactivated 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 half-time than estradiol. The biphasic dissociation kinetics of an estrogen from the receptor provides a new and sensitive criterion for measuring receptor activation.
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D004964:Estriol / Q000378:metabolism; D005260:Female; D007700:Kinetics; D008024:Ligands; D011960:Receptors, Estrogen / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism
D008024:Ligands; D011960:Receptors, Estrogen; D004958:Estradiol; D004964:Estriol