Anti-steroidogenic factor ARR19 inhibits testicular steroidogenesis through the suppression of Nur77 transactivation.
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.
Qamar
Imteyaz
I
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
Gong
Eun-Yeung
EY
Kim
Yeawon
Y
Song
Chin-Hee
CH
Lee
Hyun Joo
HJ
Chun
Sang-Young
SY
Lee
Keesook
K
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*
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
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