Interactions between androgen and estrogen receptors and the effects on their transactivational properties

Interactions between androgen and estrogen receptors and the effects on their transactivational properties
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DOI:
10.1016/s0303-7207(00)00279-3
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发表时间:
2000-09-25
影响因子:
4.1
通讯作者:
Trifiro, MA
Trifiro, MA
中科院分区:
医学2区
文献类型:
--
作者:
Panet-Raymond, V;Gottlieb, B;Trifiro, MA

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雄激素和雌激素在内分泌组织中的生理作用是公认的。造成这种相互作用的生化过程尚未完全确定。我们已经证明,雄激素受体(AR)和雌激素受体-α(ERα)可以使用酵母和哺乳动物双杂交系统直接相互作用。这些相互作用发生在C端的ERα配体结合域和N端的AR反式激活结构域或全长AR之间。雌激素受体-β(ER-beta)不与空气相互作用。使用AR、ERα和ERβ表达载体以及AR或ER报告基因构建的DNA共转染研究用于鉴定和测量AR-ER相互作用的潜在功能效应。ERα与AR共表达可使AK反式激活减少35%,AR与ERα共表达可使ERα反式激活减少74%。AR和ERβ的共表达对AR或ERβ的反式激活没有明显的调节作用。综上所述,我们已经证明了AR和ERα的特定结构域在物理上相互作用,并证明了这种相互作用的功能后果。这些结果可能有助于解释雄激素和雌激素之间生理相互作用的本质。(C)2000爱思唯尔爱尔兰科学有限公司。保留所有权利。
The physiological interplay of androgen and estrogen action in endocrine tissues is well recognized. The biochemical processes responsible for this interplay have yet to be fully defined. We have demonstrated that the androgen receptor (AR) and estrogen receptor-alpha (ER alpha) can interact directly using the yeast and mammalian two-hybrid systems. These interactions occurred between the C-terminal ER alpha ligand-binding domain and either the N-terminal AR transactivational domain or the full-length AR. Estrogen receptor-beta (ER beta) did not interact with the AIR. DNA cotransfection studies employing AR, ER alpha and ER beta expression vectors and AR- or ER-reporter gene constructs were used to identify and measure potential functional effects of AR-ER interaction. Coexpression of ER alpha with AR decreased AK transactivation by 35%; coexpression of AR with ER alpha decreased ER alpha transactivation by 74%. Coexpression of AR and ER beta did not significantly modulate AR or ER beta transactivation. In summary, we have shown that specific domains of AR and ER alpha physically interact and have demonstrated the functional consequences of such interaction. These results may help explain the nature of the physiological interplay between androgens and estrogens. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.