Effects of selective estrogen receptor agonists on estrogen receptor expression in the uterus of ovariectomized rats

The aim of the present study was to investigate effects of short time treatment with estrogen receptor (ER) selective agonists on ERα, ERβ and G-protein coupled estrogen receptor-1 (GPER) expression in the uterus of ovariectomized rats. The rats were treated with either estradiol (E2), the specific ERα agonist PPT or the specific ERβ agonist DPN for 18 hrs. Uterine weights were higher after E2 or PPT treatment than after DPN or no treatment. ERα mRNA levels decreased significantly in PPT and DPN treated animals as compared to controls. Stromal ERα immunostaining was higher after E2 treatment than in controls. The ERβ mRNA level was lower in the E2 and PPT groups compared with controls. ERβ immunoreactivity was higher in the myometrium after DPN treatment than in controls. The GPER mRNA level was lower in the E2 and DPN groups as compared to the controls, whereas total protein levels did not display any change. The proliferation marker Ki67 increased after PPT treatment in stroma and myometrium, as compared to controls. Thus, uterine growth and proliferation are predominately regulated via ERα. Also ERβ expression showed regulation via ERα, while GPER expression indicated control via ERβ. This short term treatment did not result in any regulation of the total protein level as determined by Western blot. However, treatment by E2 increased ERα immunostaining in the stroma and DPN augmented ERβ immunostaining in the myometrium. Thus, the estrogen receptors in the rat uterus are differently regulated depending on the ligand and tissue type.