title: Identification of testosterone-/androgen receptor-regulated genes in mouse Sertoli cells.
abstract: Androgen and androgen receptor (AR) play important roles in male spermatogenesis and fertility, yet detailed androgen/AR signals in Sertoli cells remain unclear. To identify AR target genes in Sertoli cells, we analyzed the gene expression profiles of testis between mice lacking AR in Sertoli cells (S-AR(-/y)) and their littermate wild-type (WT) mice. Digital gene expression analysis identified 2276 genes downregulated and 2865 genes upregulated in the S-AR(-/y) mice testis compared to WT ones. To further nail down the difference within Sertoli cells, we first constructed Sertoli cell line TM4 with stably transfected AR (named as TM4/AR) and found androgens failed to transactivate AR in Sertoli TM4 and TM4/AR cells. Interestingly, additional transient transfection of AR-cDNA resulted in significant androgen responsiveness with TM4/AR cells showing 10 times more androgen sensitivity than TM4 cells. In the condition where maximal androgen response was demonstrated, we then analyzed gene expression and found the expression levels of 2313 genes were changed more than twofold by transient transfection of AR-cDNA in the presence of testosterone. Among these genes, 603 androgen-/AR-regulated genes, including 164 upregulated and 439 downregulated, were found in both S-AR(-/y) mice testis and TM4/AR cells. Using informatics analysis, the gene ontology was applied to analyze these androgen-/AR-regulated genes to predict the potential roles of androgen/AR in the process of spermatogenesis. Together, using gene analysis in both S-AR(-/y) mice testis and TM4/AR cells may help us to better understand the androgen/AR signals in Sertoli cells and their influences in spermatogenesis.
authors: The Guangdong and Shenzhen Key Lab of Male Reproductive Medicine and Genetics, Sex Hormone Research Center, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China.
authors: Qiao-Xia
authors: QX
authors: Zhang
authors: Xiao-Yan
authors: XY
authors: Zhang
authors: Zhen-Ming
authors: ZM
authors: Zhang
authors: Wei
authors: W
authors: Lu
authors: Ling
authors: L
authors: Liu
authors: Gang
authors: G
authors: Li
authors: Zhi-Ming
authors: ZM
authors: Cai
authors: Yao-Ting
authors: YT
authors: Gui
authors: Chawnshang
authors: C
authors: Chang
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics* / Q000502:physiology; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D025801:Ubiquitin; D013739:Testosterone; D018631:ras Proteins