Treatment of Rats with 17β-Estradiol or Relaxin Rapidly Inhibits Uterine Estrogen Receptor β1 and β2 Messenger Ribonucleic Acid Levels1

Abstract

Estrogen regulates the growth and differentiation of the uterus via binding to estrogen receptors (ERs), members of the nuclear receptor family of transcription factors. Two forms of ER exist: ER and ER. The former is a well-characterized mediator of estrogen-induced transcription, but the function of the latter is unclear. Recent in vitro studies suggest that both splicing forms of ER expressed in rat tissues, 1 and 2, may function as inhibitors of ER transcriptional activity. To gain insight into the role of ER in estrogen action, we examined the effects of estrogen and relaxin, a ligand-independent activator of ERs, on the expression of ER1 and ER2 mRNA in the uterus in vivo. Eighteen-day-old female rats were ovariectomized and, after recovery, treated with 17-estradiol, relaxin, or vehicle. Quantitative reverse transcription-polymerase chain reaction analyses of uterine RNA from estrogen-treated animals revealed marked decreases in the steady-state levels of the mRNAs for both ER1 and ER2 at 3, 6, and 24 h after treatment. Relaxin induced a similar effect. Neither hormone had any significant effect on ER mRNA levels. To determine if endogenous estrogen exerts this effect, we examined the expression of ERs in the uterus during the estrous cycle. Levels of both isoforms were highest at diestrus (low estrogen), were significantly lower at early proestrus (rising estrogen), reached a nadir during late proestrus (peak estrogen), and rebounded at estrus (declining estrogen). These data suggest that down-regulation of ER expression may be required for estrogen to exert its full trophic effects on the uterus.