Résumé

P2-082

The uterine and vascular actions of Estetrol delineate a distinctive profile of Estrogen Receptor alpha modulation, uncoupling nuclear and membrane activation.

Dr C. FONTAINE^a, Dr A. ABOT^a, Mlle M. BUSCATO^a, Dr A. DROUGARD^a, Dr R. SOLINHAC^a, Pr C. KNAUF^a, Dr G. FLOURIOT^b, Dr I. RAYMOND-LETRON^c, Dr J. KATZENELLENBOGEN^d, Dr B. KATZENELLENBOGEN^d, Dr G. GREENE^e, Pr JM. FOIDART^f, Pr P. GOURDY^g, Pr JF. ARNAL^a

^a INSERM 1048, Toulouse ; ^b INSERM 1085, Rennes ; ^c Ecole vétérinaire de Toulouse, Toulouse ; ^d University of Illinois, Urbana, Chicago ; ^e University of Chicago, Chicago ; ^f Université de Liège, Liège ; ^g INSERM1048, Toulouse

CONTEXT Estetrol (E₄) is an estrogen produced by the human fetal liver only during pregnancy. A recent clinical phase II study evaluating its contraceptive properties revealed that E₄ did not change the levels of hepatic-derived proteins, including coagulation factors. Thus, at variance to classically used estrogens, it might not increase thrombo-embolic events. The molecular mechanism of action of E₄ is essentially unknown, and the goal of this study was to define the nuclear/transcriptional actions versus the membrane/rapid actions in comparison to E2.

 RESULTS In this study, we show that E₄ is less potent than E2 to activate estrogen receptor alpha (ERα), but a high dose is able to modulate the transcriptional activity of ERα in the uterus, the proliferation of endometrial epithelium and to prevent atheroma. In contrast, E₄ was not only devoid of effects on endothelial healing and NO production, but it antagonized these E2 effects that are purely membrane ERα-dependent.

CONCLUSION Thus, E₄ appears not only as less potent estrogen than E2 but behaves as a natural Selective ER Modulator, and its spectrum of action as safe oral contraceptive or hormonal treatment of menopause should now be considered.

retour afficher le poster