It is suggested that phosphatidylinositol 3-kinase pathway is involved in regulation of estrogen effects in the uterus. Therefore, effects of posphatidylinositol 3-kinase blocker, wortmannin, on proliferative and morphogenetic reactions in the uterus under long-term estrogen treatment were examined. Ovariectomized mice were treated with estradiol dipropionate (4 μg per 100 g; s.c.; once a week) or vehicle and wortmannin (0.1 mg per 100 g; s.c.; once a day) or vehicle for a month. In animals treated with estradiol and wortmannin, uterine mass was decreased, abnormal uterine glands and atypical endometrial hyperplasia were found rarely. Wortmannin produced a decrease in the numbers of mitotic and bromodeoxyuridine-labelled cells in luminal and glandular epithelia, in stromal and myometrial cells. Levels of estrogen receptors-alpha and progesterone receptors in uterine epithelia, stromal and myometrial cells were increased in mice treated with estradiol and wortmannin. Expression of beta-catenin in luminal and glandular epithelia was also elevated in mice treated with estradiol and wortmannin. Thus, phosphatidylinositol 3-kinase inhibitor wortmannin diminishes proliferative and morphogenetic effects of estradiol. Action of wortmannin is associated with changes in expression of estrogen receptors-alpha, progesterone receptors and beta-catenin in the uterus. This work was supported by grant from RFBR (07-04-00023).
03 - 07 May 2008
European Society of Endocrinology