Neonatal Estrogen Receptor beta Is Important in the Permanent Inhibition of Epithelial Cell Proliferation in the Mouse Uterus

作者：Nakajima Tadaaki; Tanimoto Yuki; Tanaka Masami; Chambon Pierre; Watanabe Hajime; Iguchi Taisen; Sato Tomomi^*

来源：Endocrinology, 2015, 156(9): 3317-3328.

DOI：10.1210/en.2015-1012

Estrogen receptor alpha (ER alpha) plays a pivotal role in the mouse uterine and vaginal epithelial cell proliferation stimulated by estrogen, whereas ER beta inhibits cell proliferation. ER beta 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 ER beta, and its roles in cell proliferation in neonatal uteri and vaginae of ER beta knockout (beta ERKO) mice. ER beta 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 beta ERKO mice, cell proliferation was greater than that in wild-type animals and in uterine epithelia of 90- and 365-day-old beta ERKO mice. In addition, p27 protein, known as a cyclin-dependent kinase inhibitor, was decreased in the uteri of 90- and 365-day-old beta ERKO 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 ER beta is important in the persistent inhibition of epithelial cell proliferation with accumulation of p27 protein in the mouse uterus. Thus, suppression of ER beta function in the uterine epithelium during the neonatal period may be responsible for a risk for proliferative disease in adults.

• 出版日期2015-9