title: Sexually dimorphic expression of Dax-1 in the adrenal cortex.
abstract: BACKGROUND
  The DAX-1 (also known as AHC) gene encodes an unusual member of the nuclear receptor superfamily, and the gene product plays a pivotal role during gonadal and adrenal differentiation. Mutations of the human DAX-1 gene cause X-linked adrenal hypoplasia congenita associated with hypogonadotropic hypogonadism. However, the molecular mechanisms underlying the transcriptional regulation of the gene are not well understood.
  
  
  RESULTS
  Sexually dimorphic expression of Dax-1 (NR0B1) in the adrenal cortex was observed by RT-PCR, Western blotting and immunohistochemistry. The differential expression was abolished by gonadectomy and was restored again by sex steroid replacement. Our results suggested that the Dax-1 gene transcription is suppressed by androgens and androgen receptor (AR/NR3C4). Dax-1 gene transcription is regulated by Ad4BP/SF-1 (NR5A1), therefore we investigated the functional correlation between A4BP/SF-1 and AR. Interestingly, AR down-regulated the Dax-1 gene transcription mediated by Ad4BP/SF-1 in the presence of the ligand. DNA binding by AR was not essential for the suppressive action, however the suppression seemed to be dependent on the promoter contexts. An interaction between Ad4BP/SF-1 and AR was detected in the presence of the ligand for AR.
  
  
  CONCLUSIONS
  The present study revealed that the expression of Dax-1 in the adrenal cortex is regulated by androgen and the receptor. Interestingly, AR acts as a suppressor in the presence of the ligand through interaction with Ad4BP/SF-1.
authors.affiliation: Department of Developmental Biology, National Institute for Basic Biology, Myodaiji-cho, Okazaki 444-8585, Japan.
authors.forename: Tokuo
authors.initials: T
authors.lastname: Mukai
authors.forename: Masatomo
authors.initials: M
authors.lastname: Kusaka
authors.forename: Ken
authors.initials: K
authors.lastname: Kawabe
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Goto
authors.forename: Hajime
authors.initials: H
authors.lastname: Nawata
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
authors.forename: Ken-ichirou
authors.initials: K
authors.lastname: Morohashi
mesh_terms: D000302:Adrenal Cortex / Q000196:embryology / Q000378:metabolism*; D000728:Androgens / Q000502:physiology; D000818:Animals; D002460:Cell Line; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011944:Receptors, Androgen / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics*; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D000728:Androgens; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C539965:NR0B1 protein, human; C539966:Nr0b1 protein, mouse; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors