Flutamide depresses expression of cortactin in the ectoplasmic specialization between the Sertoli cells and spermatids in the mouse testis
Flutamide depresses expression of cortactin in the ectoplasmic specialization between the Sertoli cells and spermatids in the mouse testis
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DOI：
10.1016/j.fct.2005.12.010
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发表时间：
2006-07-01
影响因子：
4.3
通讯作者：
Mori, Chisato
中科院分区：
文献类型：
--
作者：
Anahara, Reiko;Toyama, Yoshiro;Mori, Chisato
氟他胺（FLUT）具有强大的抗雄激素活性，被用于医学领域和检测内分泌活性化合物的筛选试验。我们先前的研究表明，FLUT诱导小鼠睾丸精细胞的组织学变形和顶端外质特化（ES）的超微结构缺陷。顶端ES是介于支持细胞和生殖细胞之间的一个以行动蛋白为基础的连接结构。皮质蛋白是一种肌动蛋白结合蛋白，存在于ES的肌动蛋白层。Western blot分析显示，经flut处理的睾丸中，接触蛋白水平降低。详细分析表明，从第6期到第9期，flut处理的精管蛋白水平急剧下降。免疫组织化学和免疫电镜显示，FLUT抑制了ES根尖的皮质蛋白表达。此外，FLUT对接触定位的影响出现在治疗1天后的12 ~ 8天（约180 h）。这些结果表明，FLUT在ES的根尖处抑制了皮质蛋白的表达，具有分期特异性。因此，FLUT的初始靶点可能是支持细胞和生殖细胞之间的细胞间相互作用。据我们所知，本研究首次记录了FLUT治疗后异常根尖ES中接触蛋白表达的减少。(c) 2006 Elsevier Ltd.版权所有。
Flutamide (FLUT) has potent anti-androgenic activity and is used in the medical field and in a screening test to detect endocrinologically active compounds. Our previous study demonstrated that FLUT induced histological deformation of spermatids and ultrastructural defects of the apical ectoplasmic specialization (ES) in the mouse testis. The apical ES is an actin-based junctional structure between the Sertoli cells and germ cells. Cortactin, an actin-binding protein, is found in the actin layer of ES. The protein level of cortactin was decreased in FLUT-treated testes as shown by Western blot analysis. The detailed analysis indicated that the protein level was drastically decreased in FLUT-treated seminiferous tubules of stages from VI to IX.Immunohistochemistry and immunoelectron microscopy showed that FLUT depressed cortactin expression in the apical ES. In addition, the effect of FLUT on cortactin localization appeared between 12 h and 8 days (about 180 h) after a one-day treatment. These results suggest that FLUT depressed the expression of cortactin in the apical ES with stage specificity. Therefore, the initial target of FLUT may be the cell-cell interactions between the Sertoli and germ cells. To our knowledge, this study is the first to document the decrease of cortactin expression in the abnormal apical ES following treatment with FLUT. (c) 2006 Elsevier Ltd. All rights reserved.