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Publication : Neonatal Estrogen Receptor β Is Important in the Permanent Inhibition of Epithelial Cell Proliferation in the Mouse Uterus.

First Author  Nakajima T Year  2015
Journal  Endocrinology Volume  156
Issue  9 Pages  3317-28
PubMed ID  26020796 Mgi Jnum  J:226952
Mgi Id  MGI:5699236 Doi  10.1210/en.2015-1012
Citation  Nakajima T, et al. (2015) Neonatal Estrogen Receptor beta Is Important in the Permanent Inhibition of Epithelial Cell Proliferation in the Mouse Uterus. Endocrinology 156(9):3317-28
abstractText  Estrogen receptor alpha (ERalpha) plays a pivotal role in the mouse uterine and vaginal epithelial cell proliferation stimulated by estrogen, whereas ERbeta inhibits cell proliferation. ERbeta 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 ERbeta, and its roles in cell proliferation in neonatal uteri and vaginae of ERbeta knockout (betaERKO) mice. ERbeta 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 betaERKO mice, cell proliferation was greater than that in wild-type animals and in uterine epithelia of 90- and 365-day-old betaERKO mice. In addition, p27 protein, known as a cyclin-dependent kinase inhibitor, was decreased in the uteri of 90- and 365-day-old betaERKO 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 ERbeta is important in the persistent inhibition of epithelial cell proliferation with accumulation of p27 protein in the mouse uterus. Thus, suppression of ERbeta function in the uterine epithelium during the neonatal period may be responsible for a risk for proliferative disease in adults.
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