交易激励
雌激素受体
激素反应元件
转录因子
雌激素受体
兴奋剂
生物
雌激素
雌激素受体α
内分泌学
内科学
化学
受体
细胞生物学
基因
生物化学
医学
癌症
遗传学
乳腺癌
作者
Stefan O. Mueller,John A. Katzenellenbogen,Kenneth S. Korach
出处
期刊:Steroids
[Elsevier]
日期:2004-09-01
卷期号:69 (10): 681-686
被引量:8
标识
DOI:10.1016/j.steroids.2004.06.004
摘要
The estrogen receptor (ER) α is a hormone-inducible transcription factor that has a pivotal physiological role. Intriguingly, a clear and undisputed physiological function of the recently described ERβ remains elusive, with the exception of the ovary where a cooperative role of ERα and ERβ has been demonstrated. We have, therefore, investigated whether endogenous ERs, in particular ERβ, act as ligand-inducible transcription factors in primary ovarian cells derived from wild-type, ERα or ERβ knockout mice. Granulosa-enriched cell fractions naturally expressing ERβ and thecal cell fractions that express ERα were analyzed in transactivation assays using the vitellogenin A2 consensus estrogen response element and potent ER agonists diethylstilbestrol and S-indenestrol A. We studied also the potency-selective ERβ agonist R-indenestrol A, the pure ERα agonist and ERβ antagonist R,R-diethyl-tetrahydrochrysene and the pure ERα agonist propylpyrazole-triol. Using ER subtype-specific physiological cell models and these ER subtype-specific structural probes, we analyzed trans-activation of ERα and ERβ. This analysis revealed that endogenously expressed ERβ is indeed functional as a transcription factor, that it responds to estrogens appropriately, and that the ligands used are true ER subtype-specific probes in primary ovarian cells. In conclusion, this study demonstrates that endogenously expressed ERβ is capable of regulating gene transcription independent of ERα.
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