It is suggested that estrogen hormones involve pathways controlling histone acetylation to brought about their effects in the uterus. However, it is not known how the level of histone acetylation affect estrogen-dependent processes in the uterus, especially proliferation and morphogenetic changes. Therefore, effects of histone deacetylase blockers, trichostatin A and sodium butyrate, on proliferative and morphogenetic reactions in the uterus under long-term estrogen treatment were examined. Ovariectomized mice were treated with estradiol dipropionate (4 microg per 100 g; s.c., once a week) or vehicle and trichostatin A (0.008 mg per 100 g; s.c.; once a day) or sodium butyrate (1% in drinking water) or with no additional treatments for a month. In animals treated with estradiol and trichostatin A or sodium butyrate, uterine mass was increased, abnormal uterine glands and atypical endometrial hyperplasia were found more often. Both histone deacetylase inhibitors produced an increase 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 decreased in mice treated with estradiol with trichostatin A or sodium butyrate. Expression of beta-catenin in luminal and glandular epithelia was attenuated in mice treated with estradiol with trichostatin A or sodium butyrate. Both histone deacetylase inhibitors have similar unilateral effects, however the action of trichostatin A was more expressed than that of sodium butyrate. Thus, histone deacetylase inhibitors exert proliferative and morphogenetic effects of estradiol. Actions of trichostatin A and sodium butyrate are 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 (03-04-48000).
01 - 05 Apr 2006
European Society of Endocrinology