title: Anti-steroidogenic factor ARR19 inhibits testicular steroidogenesis through the suppression of Nur77 transactivation.
abstract: ARR19 (androgen receptor corepressor-19 kDa), a leucine-rich protein whose expression is down-regulated by luteinizing hormone and cAMP, is differentially expressed during the development of Leydig cells and inhibits testicular steroidogenesis by reducing the expression of steroidogenic enzymes. However, the molecular events behind the suppression of testicular steroidogenesis are unknown. In the present study, we demonstrate that ARR19 inhibits the transactivation of orphan nuclear receptor Nur77, which is one of the major transcription factors that regulate the expression of steroidogenic enzyme genes in Leydig cells. ARR19 physically interacts with Nur77 and suppresses Nur77-induced promoter activity of steroidogenic enzyme genes including StAR, P450c17, and 3beta-HSD in Leydig cells. Transient transfection and chromatin immunoprecipitation assays revealed that ARR19-mediated reduced expression of steroidogenic enzyme genes was likely due to the interference of SRC-1 recruitment to Nur77 protein on the promoter of steroidogenic enzyme genes. These findings suggest that ARR19 acts as a novel coregulator of Nur77, in turn regulating Nur77-induced testicular steroidogenesis, and may play an important role in the development and function of testicular Leydig cells.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Imteyaz
authors.initials: I
authors.lastname: Qamar
authors.forename: Eun-Yeung
authors.initials: EY
authors.lastname: Gong
authors.forename: Yeawon
authors.initials: Y
authors.lastname: Kim
authors.forename: Chin-Hee
authors.initials: CH
authors.lastname: Song
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sang-Young
authors.initials: SY
authors.lastname: Chun
authors.forename: Keesook
authors.initials: K
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000378:metabolism; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism; D062792:MARVEL Domain-Containing Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: C489881:Cmtm2a protein, mouse; D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012097:Repressor Proteins; D013256:Steroids; D013254:Steroid 17-alpha-Hydroxylase; D056920:Nuclear Receptor Coactivator 1
references.citation: Mol Endocrinol. 1997 Jun;11(7):891-904
references.pmid: 9178749
references.citation: Mol Cell Endocrinol. 1999 May 25;151(1-2):25-35
references.pmid: 10411317
references.citation: Endocrinology. 2001 Dec;142(12):5116-23
references.pmid: 11713204
references.citation: J Biol Chem. 1997 Apr 11;272(15):9825-32
references.pmid: 9092517
references.citation: Biol Reprod. 2001 Sep;65(3):660-71
references.pmid: 11514326
references.citation: Endocrinology. 2003 May;144(5):1958-71
references.pmid: 12697703
references.citation: Cytokine. 2002 Mar 21;17(6):301-10
references.pmid: 12061837
references.citation: J Biol Chem. 2000 Nov 24;275(47):37202-11
references.pmid: 10973968
references.citation: Mol Endocrinol. 1996 Feb;10(2):147-58
references.pmid: 8825555
references.citation: Endocr Rev. 1997 Jun;18(3):361-77
references.pmid: 9183568
references.citation: Mol Cell Biol. 2003 Feb;23(3):763-76
references.pmid: 12529383
references.citation: Methods. 2002 Jan;26(1):48-56
references.pmid: 12054904
references.citation: Rev Reprod. 2000 Sep;5(3):136-42
references.pmid: 11006163
references.citation: Mol Endocrinol. 2004 Aug;18(8):1929-40
references.pmid: 15155786
references.citation: Neuron. 1988 May;1(3):183-8
references.pmid: 3272167
references.citation: Curr Drug Targets Immune Endocr Metabol Disord. 2005 Mar;5(1):93-108
references.pmid: 15777208
references.citation: J Biol Chem. 2003 Jan 24;278(4):2294-303
references.pmid: 12431991
references.citation: Mol Cell Biol. 2004 Apr;24(7):2593-604
references.pmid: 15024051
references.citation: Endocrinology. 2001 Jul;142(7):3051-9
references.pmid: 11416027
references.citation: Int J Biochem Cell Biol. 2006 Mar;38(3):420-9
references.pmid: 16343975
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2719-24
references.pmid: 16467141
references.citation: Mol Endocrinol. 2004 Dec;18(12):2880-94
references.pmid: 15358835
references.citation: Biol Reprod. 2005 Jun;72(6):1405-15
references.pmid: 15716394
references.citation: J Biol Chem. 2001 Nov 23;276(47):43734-9
references.pmid: 11559707
references.citation: Annu Rev Biophys Biomol Struct. 2001;30:329-59
references.pmid: 11340063
references.citation: Mol Cell Biol. 1993 Feb;13(2):861-8
references.pmid: 8380897
references.citation: Endocr Rev. 2002 Apr;23(2):141-74
references.pmid: 11943741
references.citation: Gen Comp Endocrinol. 1986 Dec;64(3):321-9
references.pmid: 2948871
references.citation: J Biol Chem. 2003 Jul 4;278(27):24776-90
references.pmid: 12709428
references.citation: Endocrinology. 2003 Mar;144(3):929-36
references.pmid: 12586770
references.citation: J Biol Chem. 2007 Mar 9;282(10):7329-38
references.pmid: 17202144
references.citation: Mol Endocrinol. 2004 Jan;18(1):13-25
references.pmid: 14576337
references.citation: Mol Cell Biol. 1990 Dec;10(12):6454-9
references.pmid: 2247065
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3690-4
references.pmid: 11274386
references.citation: J Biol Chem. 2002 Sep 6;277(36):33001-11
references.pmid: 12082103
references.citation: Endocr Rev. 1999 Oct;20(5):689-725
references.pmid: 10529899
references.citation: Proc Natl Acad Sci U S A. 1988 Nov;85(22):8444-8
references.pmid: 3186734
references.citation: Mol Cell Biol. 1991 Jun;11(6):3239-46
references.pmid: 1645447
references.citation: Endocr Res. 1998 Aug-Nov;24(3-4):505-13
references.pmid: 9888531
references.citation: J Biol Chem. 1993 Nov 25;268(33):24808-12
references.pmid: 8227042
references.citation: J Biol Chem. 2009 Jul 3;284(27):18021-32
references.pmid: 19398553
references.citation: J Endocrinol. 1997 Aug;154(2):201-9
references.pmid: 9291830
references.citation: Mol Endocrinol. 1993 Aug;7(8):953-64
references.pmid: 8232315
references.citation: J Endocrinol. 2007 Sep;194(3):579-93
references.pmid: 17761897
references.citation: Mol Endocrinol. 2002 Jul;16(7):1638-51
references.pmid: 12089357