Kinetics of catechol estrogen-estrogen receptor dissociation: a possible factor underlying differences in catechol estrogen biological activity

Steroids. 1983 May;41(5):643-56. doi: 10.1016/0039-128x(83)90030-2.

Abstract

The mechanisms underlying the differences in uterotrophic potency between 2- and 4-hydroxyestrogens were explored. Doses of estradiol (E2)(10 micrograms/kg), 2-OHE2 (500 micrograms/kg) and 4-OHE2 (100 micrograms/kg) sufficient to induce near maximal cell nuclear estrogen receptor (ERn) binding were injected subcutaneously into 26 day old female rats. Uterine ERn concentrations declined more rapidly after 2-OHE2 than after E2 or 4-OHE2. E2 and 4-OHE2 both elicited a significant increase in uterine wet weight, measured at 24-36 hrs after injection. 2-OHE2 had no significant effect and neither synergized with nor antagonized the effects of simultaneously administered E2 or 4-OHE2. Under in vitro conditions at 25 degrees C, 2-hydroxyestrone (2-OHE1) and 2-OHE2 both dissociated from the receptors more rapidly than either their parent monophenolic estrogens or the corresponding 4-hydroxyestrogens. These results suggest that differences in estrogenic potency between 2- and 4-hydroxyestrogens may partly be a function of the dissociation kinetics of their estrogen receptor complexes.

Publication types

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

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • Estradiol / metabolism
  • Estradiol / pharmacology*
  • Estrone / analogs & derivatives*
  • Female
  • Hydroxyestrones / metabolism
  • Hydroxyestrones / pharmacology*
  • Kinetics
  • Rats
  • Rats, Inbred Strains
  • Receptors, Estrogen / metabolism*
  • Uterus / drug effects
  • Uterus / physiology*

Substances

  • Hydroxyestrones
  • Receptors, Estrogen
  • Estrone
  • 4-hydroxyestrone
  • Estradiol
  • 2-hydroxyestrone