Bip is a molecular link between the phase I and phase II estrogenic responses in uterus.
Bip is a molecular link between the phase I and phase II estrogenic responses in uterus.
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DOI：
10.1210/me.2006-0046
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发表时间：
2006-08
影响因子：
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通讯作者：
Sanhita Ray;Xiao-Fan Hou;Hanyang Zhou;Haibin Wang;S. Das
中科院分区：
文献类型：
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作者：
Sanhita Ray;Xiao-Fan Hou;Hanyang Zhou;Haibin Wang;S. Das
子宫雌激素作用是双相的，早期（I相）和晚期（II相）反应。然而，这些相之间的分子连接是未知的。虽然某些I相反应被认为是雌激素受体（ER）α和ER β独立的，但II相反应是ER α依赖的。我们以前观察到，在几个基因中，Bip是由雌激素诱导的小鼠子宫中的ER-独立的方式作为I期反应。Bip是分子伴侣家族的成员，在蛋白质加工中发挥作用并赋予细胞保护。然而，其在雌激素依赖性子宫生物学中的作用尚不清楚。我们在这里展示了Bip在调节子宫雌激素信号传导中的新功能。Bip在I期反应期间诱导，与雌激素介导的II期生长反应所需的ER α分子相互作用。利用体内和体外模型系统，我们发现腺病毒驱动的Bip抑制拮抗ER α介导的子宫基因转录。重要的是，下调Bip妥协雌激素依赖的第二阶段生长反应与持续的第一阶段反应。总之，Bip对于协调雌激素引起的双相反应至关重要，并作为子宫中ER α非依赖性和ER α依赖性雌激素反应之间的分子联系。
Uterine estrogenic actions are biphasic, early (phase I) and late (phase II) responses. However, the molecular linkage between these phases is not known. Although certain phase I responses are considered estrogen receptor (ER)alpha and ERbeta independent, the phase II responses are ERalpha dependent. We previously observed that among several genes Bip is induced by estrogen in the mouse uterus in an ER-independent manner as a phase I response. Bip is a member of the chaperone family and plays roles in protein processing and confers cellular protection. However, its role in estrogen-dependent uterine biology is unknown. We show here a new function of Bip in regulating estrogen signaling in the uterus. Bip, induced during the phase I responses, molecularly interacts with ERalpha required for estrogen-mediated phase II growth responses. Utilizing in vivo and in vitro model systems, we found that adenovirus-driven suppression of Bip antagonizes ERalpha-mediated uterine gene transcription. Importantly, down-regulation of Bip compromises estrogen-dependent phase II growth responses with sustained phase I responses. In conclusion, Bip is critical for coordinating estrogen-elicited biphasic responses and serves as a molecular link between ERalpha-independent and -dependent estrogenic responses in the uterus.