title: Inhibitory effect of melatonin on testosterone synthesis is mediated via GATA-4/SF-1 transcription factors.
abstract: The aim of the present study was to elucidate whether the GATA-4/SF-1 signalling pathway is involved in the inhibitory effects of melatonin on testosterone production in both the TM3 Leydig cell line and in C57BL/6J mice. In-vitro experiments demonstrated that melatonin treatment significantly reduced testosterone levels in cell culture medium (P < 0.05 or P < 0.01); and decreased intracellular cyclic adenosine monophospha accumulation (P < 0.05 or P < 0.01) and mRNA/protein expression of GATA-4, SF-1 (NR5A1), StAR, P450SCC (CYP11A1) and 3β-HSD (P < 0.05 or P < 0.01). These effects were blocked by N-acetyl-2-benzyltryptamin, a melatonin receptor antagonist. Similar effects of melatonin on testosterone production (P < 0.05 or P < 0.01) and down-regulation of transcription factors GATA-4 and SF-1 (P < 0.01) were also observed in mice treated with intratesticular injections of melatonin. Overall, the data suggest that the inhibitory effects of melatonin on testosterone production are mediated via down-regulation of GATA-4 and SF-1 expression.
authors.affiliation: School of Public Health, Medical College of Soochow University, Suzhou 215123, China; Department of Biological Science and Technology, Suzhou University of Science and Technology, Suzhou 215009, China.
authors.forename: Fenju
authors.initials: F
authors.lastname: Qin
authors.affiliation: School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Xian, 712100, China.
authors.forename: Linsen
authors.initials: L
authors.lastname: Zan
authors.affiliation: Department of Biological Science and Technology, Suzhou University of Science and Technology, Suzhou 215009, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Biological Science and Technology, Suzhou University of Science and Technology, Suzhou 215009, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Ouxi
authors.initials: O
authors.lastname: Shen
authors.affiliation: School of Public Health, Medical College of Soochow University, Suzhou 215123, China. Electronic address: tongjian@suda.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Tong
mesh_terms: D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects*; D054339:Steroidogenic Factor 1 / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis*
chemical_list: D050991:GATA4 Transcription Factor; D054339:Steroidogenic Factor 1; D013739:Testosterone; D000242:Cyclic AMP; D008550:Melatonin
keywords: GATA-4; Leydig cell; SF-1; melatonin; restosterone