title: Testicular steroidogenesis is locally regulated by androgen via suppression of Nur77.
abstract: Steroidogenesis in the testis is regulated by a negative feedback mechanism through the hypothalamus-pituitary-testis axis. Recent studies suggest that besides this long-loop regulation, testicular steroidogenesis is also locally regulated by androgen. However, the molecular mechanism behind this additional regulatory pathway has been poorly addressed. In the present study, we demonstrate that liganded androgen receptor (AR) suppresses the transcriptional activity of Nur77 on steroidogenic enzyme gene promoters, affecting testicular steroidogenesis. AR physically interacts and colocalizes with Nur77 in the nucleus in the presence of androgen. AR inhibits Nur77 transactivation by competing mainly with coactivators such as SRC-1 for Nur77 binding. These results suggest that androgen, through binding to AR, directly acts as a signal inhibiting the expression of steroidogenic enzyme genes in Leydig cells, eventually resulting in decreased testicular steroidogenesis. These findings strongly support the hypothesis that androgen acts locally to regulate testicular steroidogenesis, and may provide its action mechanism.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Chin-Hee
authors.initials: CH
authors.lastname: Song
authors.forename: Eun-Yeung
authors.initials: EY
authors.lastname: Gong
authors.forename: Ji soo
authors.initials: Js
authors.lastname: Park
authors.forename: Keesook
authors.initials: K
authors.lastname: Lee
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015971:Gene Expression Regulation, Enzymologic; D007985:Leydig Cells / Q000201:enzymology; D008297:Male; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000378:metabolism*; D013737:Testis / Q000201:enzymology*; D013739:Testosterone / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D000728:Androgens; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011944:Receptors, Androgen; D013739:Testosterone; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1