Shao Ruijin, Weijdegård Birgitta, Fernandez-Rodriguez Julia, Egecioglu Emil, Zhu Changlian, Andersson Niklas, Thurin-Kjellberg Ann, Bergh Christina, Billig Håkan
Instiute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, SE-41390 Gothenburg, Sweden.
Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E147-58. doi: 10.1152/ajpendo.00101.2007. Epub 2007 Mar 20.
Several ERbeta isoforms have been identified in human and rodent tissues, but it is unclear whether each isoform has distinctly different cellular targeting characteristics and physiological functions. We have investigated the intracellular localization and regulatory patterns for ERbeta isoforms in rat fallopian tubes. Western blot analysis reveals that two ERbeta isoforms corresponding to ERbeta1 and ERbeta2 are expressed in rat fallopian tubes. However, ERbeta2 is the predominant form of ERbeta in this tissue. High-resolution confocal imaging and immunohistochemical analysis provide ample evidence that ERbeta expression is limited almost exclusively to the ciliated epithelial cells, in contrast to ERalpha, which is widely distributed. Furthermore, within the ciliated epithelial cells, ERbeta is colocalized with beta-tubulin IV at stem portion of the cilia. We show that ERbeta2 protein expression is tightly regulated by E(2) or DPN in a time-dependent manner without changes in ERbeta1 expression. These estrogenic effects are inhibited by an ER antagonist, ICI 182,780. In addition, significant alteration of ERbeta immunoreactivity is detected only histologically in the ampullary region. Since the cilia are considered an essential determinant of tubal transport, we further demonstrate that E(2)- or DPN-induced ERbeta2 activation is associated with alterations in tubal protein expression crucial for the regulation of calcium-dependent ciliary beating. Given the coordinated regulation and interaction of ER and progesterone receptor in the cilia, we hypothesize that tubal ERbeta2 may facilitate the estrogen-mediated transport process by processing protein-protein interaction under physiological and/or pathological conditions. We show for the first time that a previously unrecognized localization of ERbeta isoform in rat fallopian tubes can combine with estrogen to individually control the expression of ER beta-isoforms in normal target tissues.
在人和啮齿动物组织中已鉴定出几种雌激素受体β（ERβ）亚型，但尚不清楚每种亚型是否具有明显不同的细胞靶向特征和生理功能。我们研究了大鼠输卵管中ERβ亚型的细胞内定位和调控模式。蛋白质免疫印迹分析显示，大鼠输卵管中表达了与ERβ1和ERβ2相对应的两种ERβ亚型。然而，ERβ2是该组织中ERβ的主要形式。高分辨率共聚焦成像和免疫组织化学分析提供了充分的证据，表明与广泛分布的ERα不同，ERβ的表达几乎仅限于纤毛上皮细胞。此外，在纤毛上皮细胞内，ERβ与β-微管蛋白IV在纤毛的茎部共定位。我们发现，ERβ2蛋白表达受到雌二醇（E₂）或二氢睾酮（DPN）的时间依赖性严格调控，而ERβ1的表达没有变化。这些雌激素效应被雌激素受体拮抗剂ICI 182,780抑制。此外，仅在组织学上检测到壶腹部区域的ERβ免疫反应性有显著改变。由于纤毛被认为是输卵管运输的重要决定因素，我们进一步证明，E₂或DPN诱导的ERβ2激活与对钙依赖性纤毛摆动调节至关重要的输卵管蛋白表达改变有关。鉴于雌激素受体和孕激素受体在纤毛中的协同调节和相互作用，我们推测输卵管ERβ2可能通过在生理和/或病理条件下处理蛋白质-蛋白质相互作用来促进雌激素介导的运输过程。我们首次表明，大鼠输卵管中ERβ亚型以前未被认识的定位可以与雌激素结合，在正常靶组织中单独控制ERβ亚型的表达。
