The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation. - Université d'Angers Accéder directement au contenu
Article Dans Une Revue EMBO Molecular Medicine Année : 2014

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

Coralie Fontaine
  • Fonction : Auteur
Aurelie J Fabre
  • Fonction : Auteur
Shyamala Rajan
  • Fonction : Auteur
Muriel Laine
  • Fonction : Auteur
Alain Milon
  • Fonction : Auteur
Isabelle Muller
  • Fonction : Auteur
  • PersonId : 1136648
Daniel Henrion
Céline Gerard
  • Fonction : Auteur
Isabelle Raymond-Letron
  • Fonction : Auteur
Philippe Valet
John A Katzenellenbogen
  • Fonction : Auteur
Geoffrey L Greene
  • Fonction : Auteur
Jean-François Arnal
  • Fonction : Auteur

Résumé

Estetrol (E4) 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 (ERα) ligand-binding domain bound to 17β-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.

Dates et versions

hal-01118028 , version 1 (18-02-2015)

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Citer

Anne Abot, Coralie Fontaine, Mélissa Buscato, Romain Solinhac, Gilles Flouriot, et al.. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation.. EMBO Molecular Medicine, 2014, 6 (10), pp.1328-46. ⟨10.15252/emmm.201404112⟩. ⟨hal-01118028⟩
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