Pillai Suresh B, Jones Jenny M, Koos Robert D
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA.
Biol Reprod. 2002 Dec;67(6):1919-26. doi: 10.1095/biolreprod.102.003392.
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.
雌激素通过与雌激素受体（ERs）结合来调节子宫的生长和分化，雌激素受体是转录因子核受体家族的成员。存在两种形式的ER：ERα和ERβ。前者是雌激素诱导转录的一个特征明确的介质，但后者的功能尚不清楚。最近的体外研究表明，在大鼠组织中表达的ERβ的两种剪接形式，β1和β2，可能作为ERα转录活性的抑制剂发挥作用。为了深入了解ERβ在雌激素作用中的作用，我们在体内研究了雌激素和松弛素（一种不依赖配体的ER激活剂）对子宫中ERβ1和ERβ2 mRNA表达的影响。18日龄雌性大鼠接受卵巢切除术，恢复后，用17β-雌二醇、松弛素或赋形剂处理。对雌激素处理动物的子宫RNA进行定量逆转录-聚合酶链反应分析显示，处理后3、6和24小时，ERβ1和ERβ2 mRNA的稳态水平显著降低。松弛素诱导了类似的效果。两种激素对ERα mRNA水平均无显著影响。为了确定内源性雌激素是否发挥这种作用，我们检查了发情周期中子宫中ERβ的表达。两种异构体的水平在动情间期（低雌激素）最高，在动情前期早期（雌激素上升）显著降低，在动情前期晚期（雌激素峰值）达到最低点，并在发情期（雌激素下降）反弹。这些数据表明，雌激素对子宫发挥其充分的营养作用可能需要下调ERβ的表达。
