Lithium treatment enhances estradiol-induced proliferation and hyperplasia formation in the uterus of mice

А. Г. Гунин, Vladimir U. Emelianov, I. U. Mironkin, M. P. Morozov, Alexei S. Tolmachev
In: European Journal of Obstetrics & Gynecology and Reproductive Biology · 2004 · vol. 114(1) , pp. 83–91 · doi:10.1016/j.ejogrb.2003.09.023 · PMID:15099877 · W2080055110
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Lithium treatment increased estradiol-induced uterine proliferation and hyperplasia in mice, associated with decreased uterine expression of estrogen receptors, beta-catenin, and glycogen synthase kinase-3beta.

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Abstract

ObjectivesIt is suggested that the Wnt/beta-catenin pathway plays a role in the regulation of estrogen action in the uterus. However, this suggestion has not been proved. Lithium can mimic increased activity of the Wnt/beta-catenin pathway by blocking the activity of glycogen synthase kinase-3beta. There are no data on the effects of lithium on estrogen-dependent processes in the uterus. This work was therefore aimed to examine the action of lithium on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments.Study designOvariectomized mice received estradiol dipropionate (2 microg per 100g; s.c.) once a week or vehicle and drank tap water with 0.05% lithium chloride or plain tap water for 2 or 30 days.ResultsIn animals treated with estradiol and lithium for a month, the incidence of atypical endometrial hyperplasia was significantly higher. In animals treated with estradiol and lithium for 2 days or for a month, uterine mass, the number of mitotic cells and BrdU-labelled cells in luminal epithelium, glandular epithelium, stromal and myometrial cells was markedly greater, whereas the levels of estrogen receptors-alpha, beta-catenin and glycogen synthase kinase-3beta were markedly lower in all uterine compartments, than in those in mice received estradiol with no lithium to drink.ConclusionsLithium treatment results in an increase in estradiol-induced proliferative and morphogenetic changes in the uterus. This action of lithium is associated with decreased expression of estrogen receptors-alpha, beta-catenin and glycogen synthase kinase-3beta in the uterus.

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