Reproductive functions of the progesterone receptor isoforms: lessons from knock-out mice
Reproductive functions of the progesterone receptor isoforms: lessons from knock-out mice
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DOI：
10.1016/s0303-7207(01)00465-8
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发表时间：
2001-06-20
影响因子：
4.1
通讯作者：
De Mayo, FJ
中科院分区：
文献类型：
--
作者：
Conneely, OM;Mulac-Jericevic, B;De Mayo, FJ
黄体酮在与妊娠建立和维持相关的各种生殖事件中起着中心协调作用。在人类和其他脊椎动物中。黄体酮的生物学活性是由来自同一基因的A （PR-A）和B （PR-B）两种蛋白介导的，它们作为黄体酮激活的转录因子，在体外表现出不同的转录调控活性。缺乏两种PR亚型的小鼠（PRKO小鼠）表现出多性生殖异常。为了解决单个亚型的生理作用，我们选择性地消融了PR-A在小鼠中的表达（PRAKO）。我们已经证明PR-B介导P的一部分生殖功能，PR-A的消融不会影响乳腺或胸腺对P的反应，但会导致卵巢和子宫功能的严重异常。对PRAKP小鼠尿液功能的分析显示，PR-B在上皮中具有意想不到的p依赖性增殖活性，并提供证据表明，该亚型的组织特异性生殖效应是由于靶基因转激活的特异性，而不是相对于PR-A的组织特异性表达差异。综上所述，我们的数据表明PR-A和PR-B在体内作为两种功能不同的转录因子，(C) 2001 Elsevier Science Ireland Ltd。版权所有。
Progesterone plays a central coordinate role in diverse reproductive events associated with establishment and maintenance of pregnancy. In humans and other vertebrates. the biological activities of progesterone are mediated by two proteins, A (PR-A) and B (PR-B) that arise from the same gene and function as progesterone activated transcription factors that exhibit different transcription regulatory activities in vitro. Mice lacking both PR isoforms (PRKO mice) exhibit pleiotropic reproductive abnormalities. To address the physiological role of the individual isoforms, we have selectively ablated PR-A expression in mice (PRAKO). We have demonstrated that PR-B mediates a subset of the reproductive functions of P. Ablation of PR-A does not affect responses of the mammary gland or thymus to P but results in severe abnormalities in ovarian and uterine function. Analysis of urine function of PRAKP mice reveals an unexpected P-dependent proliferative activity of PR-B in the epithelium and provides evidence that the tissue-specific reproductive effects of this isoform are due to specificity of target gene transactivation rather than differences in tissue-specific expression relative to PR-A. Taken together, our data indicate that PR-A and PR-B act in vivo as two functionally distinct transcription factors, (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.