Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Receptor interconversion model of hormone action. I. ATP-mediated conversion of estrogen receptors from a high to lower affinity state and its relationship to antiestrogen action

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • McNaught, R. W.
  • Raymoure, W. J.
  • Smith, Roy

publication date

  • 1986

journal

  • Journal of Biological Chemistry  Journal

abstract

  • We have previously reported that the estrogen receptor exists in three distinct states in the oviduct of the estrogen-treated chick. Since two of these forms bind estrogen and possess a number of similar properties, the intrinsic relationship between these two receptor forms has been investigated. We now show that a quantitative conversion of the high affinity (Rx) to the lower affinity (Ry) state can be induced by mild heating (30 degrees C) in the presence of estradiol and ATP, or the synthetic analogue alpha,beta-methylene adenosine triphosphate and the divalent cation Mg2+. Other nucleotides, including ADP, GTP, CTP, cAMP, and cGMP, as well as the nonhydrolyzable analogues beta,gamma-methylene adenosine triphosphate and alpha,beta-methylene adenosine diphosphate are ineffective. The conversion occurs only partially in the absence of estradiol but completely in its presence. The process is not inhibited by the protease inhibitors phenylmethylsulfonyl fluoride and alpha 2-macroglobulin, and when conversion is induced by low concentrations of ATP (1 mM), a time dependent reequilibration back to Rx occurs. These observations and the fact that the pure hormone-binding peptides Rx and Ry have similar molecular weights on sodium dodecyl sulfate-polyacrylamide gels (66,000) confirm that proteolysis is not involved in the conversion. Moreover their physical properties suggest that Rx and Ry exist in alternate conformations, with Ry being favored as a result of an ATP-mediated event involving the gamma-phosphoryl moiety. The biological relevance of the receptor conversion is suggested by studies with the antiestrogen hydroxytamoxifen. This antiestrogen binds to Rx with higher affinity than either estradiol or diethylstilbestrol but with low affinity to Ry. Hydroxytamoxifen also inhibits the conversion of Rx to Ry. Since this antiestrogen is a complete antagonist in the chick oviduct and prevents estradiol-induced stimulation of ovalbumin gene transcription, it is speculated that Rx to Ry conversion is crucial for ovalbumin gene activation and that Rx may act as a transcriptional repressor. Furthermore, since Rx and Ry both bind to nuclei and DNA, it is proposed that the presence of Ry is a better predictor of ovalbumin gene activation than DNA binding alone.

subject areas

  • Animals
  • Binding, Competitive
  • Chickens
  • Diethylstilbestrol
  • Estrogen Antagonists
  • Female
  • Kinetics
  • Models, Biological
  • Oviducts
  • Receptors, Cell Surface
  • Receptors, Estrogen
  • Tamoxifen
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0021-9258

PubMed ID

  • 3023378
scroll to property group menus

Additional Document Info

start page

  • 7011

end page

  • 7017

volume

  • 261

issue

  • 36

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support