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Int J Gynecol Cancer ; 13(4): 485-96, 2003.
Article in English | MEDLINE | ID: mdl-12911726

ABSTRACT

This work examined the effect of chorionic gonadotropin on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments. Ovariectomized mice received a single injection with estradiol dipropionate (2 micro g per 100 g; subcutaneously, sc) or vehicle and injections with human chorionic gonadotropin (10 IU per 100 g; sc) or vehicle twice a day for 2 days. Other groups of animals received injections with estradiol once a week or vehicle and injections with chorionic gonadotropin or vehicle once a day for 30 days. The uteri were removed 48 h after the last estradiol or vehicle injection. In animals treated with estradiol and chorionic gonadotropin for a month, the incidence of atypical endometrial hyperplasia was significantly higher. In animals treated with estradiol and chorionic gonadotropin for 2 days or for a month, uterine mass was slightly increased, the number of mitotic cells and BrdU-labeled cells was greater in luminal epithelium, glandular epithelium, stromal and myometrial cells, whereas the expression of estrogen receptors-alpha was lower in all uterine compartments, than in control. In mice who received estradiol and chorionic gonadotropin for 2 days, levels of beta-catenin and glycogen synthase kinase-3beta in luminal and glandular epithelia were lower. In animals treated with estradiol and chorionic gonadotropin for a month, the level of beta-catenin was slightly higher, and the expression of glycogen synthase kinase-3beta was lower in luminal and glandular epithelia. Thus, chorionic gonadotropin exerts estradiol-induced proliferative and morphogenetic changes in the uterus. This action of chorionic gonadotropin is associated with decreased expression of estrogen receptors-alpha and with changes in expression of beta-catenin and glycogen synthase kinase-3beta in the uterus.


Subject(s)
Chorionic Gonadotropin/pharmacology , Endometrial Hyperplasia/etiology , Endometrial Hyperplasia/pathology , Estradiol/pharmacology , Animals , Biomarkers/analysis , Biopsy, Needle , Cytoskeletal Proteins/analysis , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Interactions , Female , Glycogen Synthase Kinases/analysis , Immunohistochemistry , Injections, Subcutaneous , Mice , Mice, Inbred Strains , Ovariectomy , Random Allocation , Reference Values , Sensitivity and Specificity , Trans-Activators/analysis , Uterus/drug effects , Uterus/pathology , beta Catenin
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