Binding of 2-hydroxyestradiol and 4-hydroxyestradiol to estrogen receptors from human breast cancers

J Steroid Biochem. 1989 Apr;32(4):485-92. doi: 10.1016/0022-4731(89)90380-4.


The binding of catechol estrogens, epoxyenones and methoxyestrogens was evaluated using estrogen receptors in cytosol prepared from human breast cancers. The relative affinity of 2-hydroxyestradiol, a metabolite formed in vitro from estradiol-17 beta by breast cancer cells, was indistinguishable from that of estradiol-17 beta. 4-Hydroxyestradiol, which is also a metabolite of estradiol-17 beta, associated with the estrogen receptor with a relative affinity approximately 1.5-fold greater than that of estradiol-17 beta. Epoxyenones and methoxyestrogens were weak competitors compared to the binding of estradiol-17 beta, exhibiting relative affinities 3% or less than the affinity of estradiol-17 beta. Sucrose density gradient centrifugation revealed that both 2- and 4-hydroxyestradiol inhibited the binding of estradiol-17 beta to both the 4S and 8S isoforms of the estrogen receptor in a competitive manner, with a Ki = 0.94 nM for 2-hydroxyestradiol and a Ki = 0.48 nM for 4-hydroxyestradiol. It can be concluded that these data demonstrate a specific receptor-mediated estrogenic action for both of these catechol estrogens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding, Competitive
  • Breast Neoplasms / metabolism*
  • Centrifugation, Density Gradient
  • Cytosol / metabolism
  • Estradiol / analogs & derivatives*
  • Estradiol / metabolism
  • Estradiol / pharmacology
  • Estrogens, Catechol / metabolism*
  • Female
  • Humans
  • Kinetics
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / isolation & purification
  • Receptors, Estrogen / metabolism*
  • Tumor Cells, Cultured / metabolism


  • Estrogens, Catechol
  • Receptors, Estrogen
  • Estradiol
  • 2-hydroxyestradiol
  • 4-hydroxyestradiol