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

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: ERa and ERb. 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 ERb expressed in rat tissues, b1 and b2, may function as inhibitors of ERa transcriptional activity. To gain insight into the role of ERb in estrogen action, we examined the effects of estrogen and relaxin, a ligand-independent activator of ERs, on the expression of ERb1 and ERb2 mRNA in the uterus in vivo. Eighteen-day-old female rats were ovariectomized and, after recovery, treated with 17b-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 ERb1 and ERb2 at 3, 6, and 24 h after treatment. Relaxin induced a similar effect. Neither hormone had any significant effect on ERa mRNA levels. To determine if endogenous estrogen exerts this effect, we examined the expression of ERbs 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 ERb expression may be required for estrogen to exert its full trophic effects on the uterus. estradiol, estradiol receptor, gene regulation, relaxin, uterus