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


METHODS
Ovariectomized 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.


RESULTS
In 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.


CONCLUSIONS
Lithium 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.
Gunin
Andrei G
AG
Department of Histology, Medical School Chuvash State University, 428034 Cheboksary, Russia. drgunin@mail.ru
Emelianov
Vladimir U
VU
Mironkin
Igor U
IU
Morozov
Mikhail P
MP
Tolmachev
Alexei S
AS
D000284:Administration, Oral; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004714:Endometrial Hyperplasia / Q000473:pathology*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007279:Injections, Subcutaneous; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D010052:Ovariectomy; D011897:Random Allocation; D011960:Receptors, Estrogen / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000473:pathology; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D011960:Receptors, Estrogen; D015534:Trans-Activators; D051176:beta Catenin; D004958:Estradiol; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride