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: ERalpha and ERbeta. 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 ERbeta expressed in rat tissues, beta1 and beta2, may function as inhibitors of ERalpha transcriptional activity. To gain insight into the role of ERbeta in estrogen action, we examined the effects of estrogen and relaxin, a ligand-independent activator of ERs, on the expression of ERbeta1 and ERbeta2 mRNA in the uterus in vivo. Eighteen-day-old female rats were ovariectomized and, after recovery, treated with 17beta-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 ERbeta1 and ERbeta2 at 3, 6, and 24 h after treatment. Relaxin induced a similar effect. Neither hormone had any significant effect on ERalpha mRNA levels. To determine if endogenous estrogen exerts this effect, we examined the expression of ERbetas 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 ERbeta expression may be required for estrogen to exert its full trophic effects on the uterus.

Relaxin (RLX) and estrogen affect estrogen receptor α, vascular endothelial growth factor, and RLX receptor expression in the neonatal porcine uterus and cervix

“…Observations are consistent with the fact that, in the absence of RLX, myometrial ERa expression was attenuated in RLX-null mice during late pregnancy (Siebel et al 2003). By contrast, studies in rats have shown that RLX decreased uterine ERb (ESR2) mRNA levels without affecting ERa (ESR1) mRNA levels (Pillai et al 2002). Moreover, in the cervix and vagina of RLX-null mice, chronic infusion of RLX had no effect on ERa gene expression and decreased ERb mRNA in late gestation (Parry et al 2005).…”

Locally produced relaxin may affect testis and vas deferens function in rats

“…Relaxin affects expression of estrogen receptors in several tissues (Pillai et al 2002, Siebel et al 2003, Yan et al 2008, but in vitro treatment of the vas deferens with 100 ng/ml relaxin did not significantly change the levels of transcripts for the estrogen receptors Esr1, Esr2, and Gper (Fig. 6B).…”

Estrogen synthesis in the hippocampus

“…Knowing from the reproductive system that the expression of ERs, being ligand-inducible transcriptions factors, is regulated by estrogen (Murata et al 2003;Pillai et al 2002;Xiao and Goff 1999) and that this dependency has also been proven for various brain regions (Gundlah et al 2000;Schreihofer et al 2000;Tena-Sempere et al 2004), we treated the primary hippocampal neurons with estradiol. This treatment resulted in an upregulation of ERα and a downregulation of ERβ, as immunohistochemistry and subsequent semiquantitative image analysis showed.…”