> Details

Abot, Anne; Fontaine, Coralie; Buscato, Mélissa; Solinhac, Romain; Flouriot, Gilles; Fabre, Aurélie; Drougard, Anne; Rajan, Shyamala; Laine, Muriel; Milon, Alain; Muller, Isabelle; Henrion, Daniel; Adlanmerini, Marine; Valéra, Marie‐Cécile; Gompel, Anne; Gerard, Céline; Péqueux, Christel; Mestdagt, Mélanie; Raymond‐Letron, Isabelle; Knauf, Claude; Ferriere, François; Valet, Philippe; Gourdy, Pierre; Katzenellenbogen, Benita S; [...]

The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation
  • Contributor: Abot, Anne; Fontaine, Coralie; Buscato, Mélissa; Solinhac, Romain; Flouriot, Gilles; Fabre, Aurélie; Drougard, Anne; Rajan, Shyamala; Laine, Muriel; Milon, Alain; Muller, Isabelle; Henrion, Daniel; Adlanmerini, Marine; Valéra, Marie‐Cécile; Gompel, Anne; Gerard, Céline; Péqueux, Christel; Mestdagt, Mélanie; Raymond‐Letron, Isabelle; Knauf, Claude; Ferriere, François; Valet, Philippe; Gourdy, Pierre; Katzenellenbogen, Benita S; [...]
  • imprint: Springer Science and Business Media LLC, 2014
  • Published in: EMBO Molecular Medicine
  • Language: English
  • DOI: 10.15252/emmm.201404112
  • ISSN: 1757-4676; 1757-4684
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Estetrol (E<jats:sub>4</jats:sub>) is a natural estrogen with a long half‐life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (<jats:styled-content style="fixed-case">ER</jats:styled-content>α) ligand‐binding domain bound to 17β‐estradiol (E<jats:sub>2</jats:sub>) and E<jats:sub>4</jats:sub> are very similar, as well as their capacity to activate the two activation functions <jats:styled-content style="fixed-case">AF</jats:styled-content>‐1 and <jats:styled-content style="fixed-case">AF</jats:styled-content>‐2 and to recruit the coactivator <jats:styled-content style="fixed-case">SRC</jats:styled-content>3. <jats:italic>In vivo</jats:italic> administration of high doses of E<jats:sub>4</jats:sub> stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear <jats:styled-content style="fixed-case">ER</jats:styled-content>α actions. However, E<jats:sub>4</jats:sub> failed to promote endothelial <jats:styled-content style="fixed-case">NO</jats:styled-content> synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane‐initiated steroid signaling (<jats:styled-content style="fixed-case">MISS</jats:styled-content>). Furthermore, E<jats:sub>4</jats:sub> antagonized E<jats:sub>2</jats:sub> <jats:styled-content style="fixed-case">MISS</jats:styled-content>‐dependent effects in endothelium but also in <jats:styled-content style="fixed-case">MCF</jats:styled-content>‐7 breast cancer cell line. This profile of <jats:styled-content style="fixed-case">ER</jats:styled-content>α activation by E<jats:sub>4</jats:sub>, uncoupling nuclear and membrane activation, characterizes E<jats:sub>4</jats:sub> as a selective <jats:styled-content style="fixed-case">ER</jats:styled-content> modulator which could have medical applications that should now be considered further.</jats:p>
  • Access State: Open Access