Estrogen receptor (ER)-β reduces ERα-regulated gene transcription, supporting a "Ying Yang" relationship between ERα and ERβ in mice
Estrogen receptor (ER)-β reduces ERα-regulated gene transcription, supporting a "Ying Yang" relationship between ERα and ERβ in mice
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DOI：
10.1210/me.2002-0206
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发表时间：
2003-02-01
影响因子：
--
通讯作者：
Ohlsson, C
中科院分区：
文献类型：
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作者：
Lindberg, MK;Movérare, S;Ohlsson, C
雌激素对成人骨代谢的调节具有重要作用。本研究的目的是确定雌激素受体β（ER β）在体内对骨中雌激素调节的转录活性的作用。雌激素在卵巢切除小鼠骨中的作用使用包括9400个基因的微阵列分析来确定。在野生型（WT）小鼠中被雌激素增加的大多数基因（95% = 240个基因）在ER β失活小鼠中也被雌激素增加。有趣的是，雌激素对这些基因mRNA水平的平均刺激作用在ER β失活小鼠中比WT小鼠高85%，表明ER β降低了骨中雌激素受体α（ER α）调节的基因转录。雌激素对ER α失活小鼠雌激素调节的骨基因的平均刺激作用介于WT和ER α双失活小鼠之间。因此，在ER α存在的情况下，ER β抑制ER α介导的基因转录，而在ER α不存在的情况下，它可以部分取代ER α。总之，我们在体内的数据表明，ER β的一个重要的生理作用是调节ER α介导的基因转录支持“阴阳”之间的关系ER α和ER β在小鼠中。
Estrogen is of importance for the regulation of adult bone metabolism. The aim of the present study was to determine the role of estrogen receptor-beta (ERbeta) in vivo on global estrogen-regulated transcriptional activity in bone. The effect of estrogen in bone of ovariectomized mice was determined using microarray analysis including 9400 genes. Most of the genes (95% = 240 genes) that were increased by estrogen in wild-type (WT) mice were also increased by estrogen in ERbeta-inactivated mice. Interestingly, the average stimulatory effect of estrogen on the mRNA levels of these genes was 85% higher in ERbeta-inactivated than in WT mice, demonstrating that ERbeta reduces estrogen receptor-alpha (ERalpha)-regulated gene transcription in bone. The average stimulatory effect of estrogen on estrogen-regulated bone genes in ERalpha-inactivated mice was intermediate between that seen in WT and ERalphabeta double-inactivated mice. Thus, ERbeta inhibits ERalpha-mediated gene transcription in the presence of ERalpha, whereas, in the absence of ERalpha, it can partially replace ERalpha. In conclusion, our in vivo data indicate that an important physiological role of ERbeta is to modulate ERalpha-mediated gene transcription supporting a "Ying Yang" relationship between ERalpha and ERbeta in mice.