Developmental and reproductive function of estrogen signaling

雌激素及其受体（ERα和ERβ）不仅对女性的正常生理功能是必需的，而且对男性的生殖系统、性行为、骨骼的维持和心血管系统等生理功能也是必需的。一般来说，雌激素的生理作用是由雌激素受体介导的雌激素应答基因的转录调节的。到目前为止，雌激素作用的具体机制仍不清楚。本实验利用重组腺病毒载体和/或条件性转基因小鼠，分别表达人ERα和ER β的组成型活性成分ca ERα和ER β，研究雌激素在小鼠体内的功能获得。另一种策略是通过使用Cre/loxP系统的转基因小鼠“条件性获得功能”。这些转基因细胞在wo/Cre重组酶处理前表达报告基因（nlsGFP/DsRed 2），在wo/Cre重组酶处理后分别表达caERα和caERβ。Cre重组酶有可能选择性地激活雌激素信号在时间和器官中的作用。最后，我们的目标是通过体内“选择性功能的获得/丧失”来揭示雌激素信号的生理作用。在该项目中，我们表明efp（雌激素应答指蛋白）通过蛋白水解14-3-3 σ（其为细胞周期的负调节因子）是乳腺肿瘤中细胞增殖所需的（Nature，417，871-875，2002）。

Estrogen and its receptors (ERα and ERβ) are not only essential in female for normal function, but also necessary in male function such as reproductive tract, sexual behavior, maintenance of the skeleton, and cardiovascular system. In general, physiological estrogen action is regulated the transcription of estrogen responsive genes mediated by estrogen receptors. So far, the mechanism of specific estrogen action is still not clear. Simple question is what is estrogen action, and how to make specific estrogen action in vivo.In this experiment, we have focused on gain of function in mouse in vivo by using recombinant adenovirus vector and/or conditional transgenic mice, which expressed constitutive active form human ERα and ERβ, such as ca ERα and ERβ, respectively. Alternative strategy was "conditional gain of function" by using transgenic mice with Cre/loxP system. These transgenics were expressed the reporter genes (nlsGFP/DsRed2) before treated wo/Cre recombinase, were expressed the caERα and caERβ after treated w/Cre, respectively. It was possible to activate the estrogen signaling in the timing and organs selectively, treated with Cre recombinase.Finally, our goal is unveiled with the physiological role of estrogen signaling by through "selective gain/loss of function" in vivo. In this projects, we show that efp (estrogen responsive finger protein) is required for cell proliferation in mammary tumor by through the proteolysis 14-3-3 sigma which is negative regulator cell cycle (Nature, 417, 871-875, 2002).