Fiche publication
Date publication
avril 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Cheong RY, Porteous R, Chambon P, Abraham I, Herbison AE
Lien Pubmed
Résumé
The negative feedback mechanism through which 17beta-estradiol (E2) acts to suppress the activity of the GnRH neurons remains unclear. Using inducible and cell-specific genetic mouse models, we examined the estrogen receptor (ER) isoforms expressed by neurons that mediate acute estrogen negative feedback. Adult female mutant mice in which ERalpha was deleted from all neurons in the neonatal period failed to exhibit estrous cycles or negative feedback. Adult mutant female mice with neonatal neuronal ERbeta deletion exhibited normal estrous cycles, but a failure of E2 to suppress LH secretion was seen in ovariectomized mice. Mutant mice with a GnRH neuron-selective deletion of ERbeta exhibited normal cycles and negative feedback, suggesting no critical role for ERbeta in GnRH neurons in acute negative feedback. To examine the adult roles of neurons expressing ERalpha, an inducible tamoxifen-based Cre-LoxP approach was used to ablate ERalpha from neurons that express calmodulin kinase IIalpha in adults. This resulted in mice with no estrous cycles, a normal increase in LH after ovariectomy, but an inability of E2 to suppress LH secretion. Finally, acute administration of ERalpha- and ERbeta-selective agonists to adult ovariectomized wild-type mice revealed that activation of ERalpha suppressed LH secretion, whereas ERbeta agonists had no effect. This study highlights the differences in adult reproductive phenotypes that result from neonatal vs adult ablation of ERalpha in the brain. Together, these experiments expand previous global knockout studies by demonstrating that neurons expressing ERalpha are essential and probably sufficient for the acute estrogen negative feedback mechanism in female mice.
Référence
Endocrinology. 2014 Apr;155(4):1418-27
