title: Identification of Hsf1 as a novel androgen receptor-regulated gene in mouse Sertoli cells.
abstract: 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.
authors.affiliation: Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, China; Department of Urological Surgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Lai
authors.forename: Cailing
authors.initials: C
authors.lastname: Li
authors.forename: Qiaoxia
authors.initials: Q
authors.lastname: Zhang
authors.forename: Weiren
authors.initials: W
authors.lastname: Huang
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Duan
authors.forename: Zhimao
authors.initials: Z
authors.lastname: Jiang
authors.forename: Xianxin
authors.initials: X
authors.lastname: Li
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.forename: Lisha
authors.initials: L
authors.lastname: Mou
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Gui
mesh_terms: D000818:Animals; D002460:Cell Line; D018834:Chaperonin 60 / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D050957:HSP110 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*; D013739:Testosterone / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018834:Chaperonin 60; D004268:DNA-Binding Proteins; D050957:HSP110 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; C490783:Hsp105 protein, mouse; C557066:Hspd1 protein, mouse; D024101:Mitochondrial Proteins; D011944:Receptors, Androgen; D014157:Transcription Factors; D013739:Testosterone