title: Estrogen receptors and endothelium.
abstract: Estrogens, and in particular 17beta-estradiol (E2), play a pivotal role in sexual development and reproduction and are also implicated in a large number of physiological processes, including the cardiovascular system. Both acetylcholine-induced and flow-dependent vasodilation are preserved or potentiated by estrogen treatment in both animal models and humans. Indeed, E2 increases the endothelial production of nitric oxide and prostacyclin and prevents early atheroma through endothelial-mediated mechanisms. Furthermore, whereas it prevents endothelial activation, E2 potentiates the ability of several subpopulations of the circulating or resident immune cells to produce proinflammatory cytokines. The balance between these 2 actions could determine the final effect in a given pathophysiological process. E2 also promotes endothelial healing, as well as angiogenesis. Estrogen actions are essentially mediated by 2 molecular targets: estrogen receptor-alpha (ERalpha) and ERbeta. The analysis of mouse models targeted for ERalpha or ERbeta demonstrated a prominent role of ERalpha in vascular biology. ERalpha directly modulates transcription of target genes through 2 activation functions (AFs), AF-1 and AF-2. Interestingly, an AF-1-deficient ERalpha isoform can be physiologically expressed in the endothelium and appears sufficient to mediate most of the vasculoprotective actions of E2. In contrast, AF-1 is necessary for the E2 actions in reproductive targets. Thus, it appears conceivable to uncouple the vasculoprotective and sexual actions with appropriate selective ER modulators.
authors.affiliation: INSERM U858-I2MC, Faculté de Médecine, Université de Toulouse et Centre Hospitalier Universitaire, de Toulouse, BP 84225, 31432 Toulouse Cedex 4, France. Jean-Francois.Arnal@inserm.fr
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Arnal
authors.forename: Coralie
authors.initials: C
authors.lastname: Fontaine
authors.forename: Audrey
authors.initials: A
authors.lastname: Billon-Galés
authors.forename: Julie
authors.initials: J
authors.lastname: Favre
authors.forename: Henrik
authors.initials: H
authors.lastname: Laurell
authors.forename: Françoise
authors.initials: F
authors.lastname: Lenfant
authors.forename: Pierre
authors.initials: P
authors.lastname: Gourdy
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D046468:Sexual Development; D015398:Signal Transduction; D014945:Wound Healing
chemical_list: D018836:Inflammation Mediators; D011960:Receptors, Estrogen; D004958:Estradiol