title: ARR19 (androgen receptor corepressor of 19 kDa), an antisteroidogenic factor, is regulated by GATA-1 in testicular Leydig cells.
abstract: ARR19 (androgen receptor corepressor of 19 kDa), which encodes for a leucine-rich protein, is expressed abundantly in the testis. Further analyses revealed that ARR19 was expressed in Leydig cells, and its expression was differentially regulated during Leydig cell development. Adenovirus-mediated overexpression of ARR19 in Leydig cells inhibited testicular steroidogenesis, down-regulating the expression of steroidogenic enzymes, which suggests that ARR19 is an antisteroidogenic factor. Interestingly, cAMP/luteinizing hormone attenuated ARR19 expression in a fashion similar to that of GATA-1, which was previously reported to be down-regulated by cAMP. Sequence analysis of the Arr19 promoter revealed the presence of two putative GATA-1 binding motifs. Further analyses with 5' deletion and point mutants of putative GATA-1 binding motifs showed that these GATA-1 binding sites were critical for high promoter activity. CREB-binding protein coactivated GATA-1 and markedly increased the activity of the Arr19 promoter. Both GATA-1 and CREB-binding proteins occupied the GATA-1 motifs within the Arr19 promoter, which was repressed by cAMP treatment. Altogether, these findings demonstrate that ARR19 is the target gene of GATA-1 and suggest that ARR19 gene expression in testicular Leydig cells is regulated by luteinizing hormone/cAMP signaling via the control of GATA-1 expression, resulting in the control of testicular steroidogenesis.
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: Eunsook
authors.initials: E
authors.lastname: Park
authors.forename: Eun-Yeung
authors.initials: EY
authors.lastname: Gong
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Keesook
authors.initials: K
authors.lastname: Lee
mesh_terms: D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007985:Leydig Cells / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism; D062792:MARVEL Domain-Containing Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D000728:Androgens; C489881:Cmtm2a protein, mouse; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D007986:Luteinizing Hormone; D000242:Cyclic AMP