Estrogen enhances endometrial estrogen receptor gene expression by a posttranscriptional mechanism in the ovariectomized ewe.

Prior influence of estrogen is required for many physiological effects of steroid hormones. This study addresses positive autoregulation of estrogen receptor gene expression in endometrium. Groups of ovariectomized ewes (n = 6) were treated with a single i.m. injection of 50 micrograms 17 beta-estradiol for 6, 12, 24, or 48 h or of vehicle for 24 h (control) prior to collection of endometrium. Three ewes received a regimen of estradiol-progesterone-estradiol (EPE) designed to mimic the estrous cycle. Northern analysis of endometrial RNA using an ovine estrogen receptor complementary RNA probe indicated that estradiol increased (p < 0.0001) estrogen receptor messenger RNA abundance over time to be 5-fold greater at 24 h postinjection. This effect also occurred after a period of progesterone dominance in EPE ewes (p < 0.05). Ribonuclease protection assays with a complementary RNA probe for the ovine progesterone receptor demonstrated that estradiol treatment increased progesterone receptor messenger RNA abundance at 48 h (p < 0.005). Nuclear runoff analyses indicated that whereas estradiol enhanced the transcription rates of progesterone receptor (p < 0.1) and 28S ribosomal RNA genes (p < 0.002), activity of the estrogen receptor gene was unchanged (p > 0.25). These results suggest that a physiological dose of estradiol, similar to the preovulatory surge of estrogen, up-regulates endometrial estrogen receptor gene expression by a posttranscriptional mechanism.