Identification of Hsf1 as a novel androgen receptor‐regulated gene in mouse Sertoli cells
Identification of Hsf1 as a novel androgen receptor‐regulated gene in mouse Sertoli cells
复制标题
DOI：
10.1002/mrd.22318
复制
发表时间：
2014-06
影响因子：
2.5
通讯作者：
Lihua Yang;Yadong Wang;Qiang Zhang;Y. Lai;Cailing Li;Qiaoxia Zhang;Weiren Huang;Yonggang Duan;Zhi-mao Jiang;Xianxin Li;Z. Cai;Lisha Mou;Yaoting Gui
中科院分区：
文献类型：
--
作者：
Lihua Yang;Yadong Wang;Qiang Zhang;Y. Lai;Cailing Li;Qiaoxia Zhang;Weiren Huang;Yonggang Duan;Zhi-mao Jiang;Xianxin Li;Z. Cai;Lisha Mou;Yaoting Gui
雄激素信号转导在精子发生中起着至关重要的作用，但很少有下游靶点已被确定。在当前的研究中，我们通过定量真实的时间PCR发现，与野生型小鼠相比，支持细胞选择性雄激素受体敲除（S-AR −/y）小鼠睾丸中热休克转录因子1（Hsf 1）的表达增加，并且基于免疫荧光分析，S-AR −/y支持细胞中HSF 1的表达显著增加。体外细胞培养研究表明，睾酮抑制TM 4细胞（一种小鼠支持细胞系）中Hsf 1的表达。此外，荧光素酶试验，电泳迁移率变动试验，染色质免疫沉淀试验表明，睾酮抑制Hsf 1的表达，促进雄激素受体的结合Hsf 1启动子。我们的实验还表明，睾酮介导的Hsf 1转录抑制下调热休克蛋白HSP 105和HSP 60的表达。综上所述，这些结果表明，Hsf 1是一个新的目标雄激素受体在小鼠支持细胞，睾酮及其受体调节精子发生的过程中，部分通过抑制Hsf 1的表达。摩尔Reprod. Dev. 81：514-523，2014.© 2014 Wiley Periodicals，Inc.
Androgen signaling plays a crucial role in spermatogenesis, yet few downstream targets for this signaling pathway have been identified. In the current study, we found that the expression of heat‐shock transcription factor 1 (Hsf1) was increased in the testes of Sertoli cell‐selective androgen receptor knockout (S‐AR−/y) mice compared with wild‐type mice by quantitative real‐time PCR, and the expression of HSF1 in the S‐AR−/y Sertoli cells was significantly increased, based on immunofluorescence analysis. In vitro cell‐culture studies showed that testosterone repressed the expression of Hsf1 in TM4 cells, a mouse Sertoli cell line. Moreover, a luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay showed that testosterone repressed Hsf1 expression by facilitating the binding of androgen receptor to the Hsf1 promoter. Our experiments also demonstrated that testosterone‐mediated inhibition of Hsf1 transcription down‐regulated the expression of heat‐shock proteins HSP105 and HSP60. Taken together, these results reveal that Hsf1 is a novel target of androgen receptor in mouse Sertoli cells, and testosterone and its receptor regulate the process of spermatogenesis partially by inhibiting Hsf1 expression. Mol. Reprod. Dev. 81: 514–523, 2014. © 2014 Wiley Periodicals, Inc.