Neonatal Estrogen Receptor β Is Important in the Permanent Inhibition of Epithelial Cell Proliferation in the Mouse Uterus.
Fiche publication
Date publication
septembre 2015
Journal
Endocrinology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Nakajima T, Tanimoto Y, Tanaka M, Chambon P, Watanabe H, Iguchi T, Sato T
Lien Pubmed
Résumé
Estrogen receptor α (ERα) plays a pivotal role in the mouse uterine and vaginal epithelial cell proliferation stimulated by estrogen, whereas ERβ inhibits cell proliferation. ERβ mRNA is expressed in neonatal uteri and vaginae; however, its functions in neonatal tissues have not been ascertained. In this study, we investigated the ontogenic mRNA expression and localization of ERβ, and its roles in cell proliferation in neonatal uteri and vaginae of ERβ knockout (βERKO) mice. ERβ mRNA and protein were abundant in the uterine and vaginal epithelia of 2-day-old mice and decreased with age. In uterine and vaginal epithelia of 2-day-old βERKO mice, cell proliferation was greater than that in wild-type animals and in uterine epithelia of 90- and 365-day-old βERKO mice. In addition, p27 protein, known as a cyclin-dependent kinase inhibitor, was decreased in the uteri of 90- and 365-day-old βERKO mice. Inhibition of neonatal ERs by ICI 182780 (an ER antagonist) treatment stimulated cell proliferation and decreased p27 protein in the uterine luminal epithelium of 90-day-old mice but not in the vaginal epithelium. These results suggest that neonatal ERβ is important in the persistent inhibition of epithelial cell proliferation with accumulation of p27 protein in the mouse uterus. Thus, suppression of ERβ function in the uterine epithelium during the neonatal period may be responsible for a risk for proliferative disease in adults.
Mots clés
Animals, Animals, Newborn, Apoptosis, Cell Cycle, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p27, metabolism, Epithelial Cells, physiology, Estradiol, analogs & derivatives, Estrogen Receptor alpha, metabolism, Estrogen Receptor beta, physiology, Female, Gene Expression, Intercellular Signaling Peptides and Proteins, metabolism, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Uterus, physiology, Vagina, physiology
Référence
Endocrinology. 2015 Sep;156(9):3317-28