Role of transcription factors Ad4bp/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia.
BACKGROUND
Ad4bp/SF-1 and DAX-1 are orphan members of the nuclear hormone receptor superfamily of transcription factors. In order to obtain better understandings of human testicular steroidogenesis and spermatogenesis, we examined the expression levels of both factors in human normal and idiopathic azoospermic testes and investigated their physical meaning.


METHODS
First, we examined the expression level of Ad4bp/SF-1 and DAX-1 by quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting analysis using eight normal human testicular tissues from infants to adults. Second, we performed quantitative RT-PCR using testicular biopsy samples obtained from 22 idiopathic azoospermic patients to examine the expression of Ad4bp/SF-1 and DAX-1, and analysed the correlation between the expression levels of both factors and the serum hormone levels or histological evaluation to study their potential correlation with steroidogenesis and spermatogenesis on idiopathic azoospermia.


RESULTS
The expression levels of both factors in the normal testes increased with testicular development. Ad4bp/SF-1 was abundantly expressed in Leydig cell, whereas DAX-1 was expressed in Sertoli cells. The expression level of Ad4bp/SF-1 in idiopathic azoospermic patients testes positively correlated with serum testosterone (P < 0.05). The average expression levels of DAX-1 mRNA for patients with maturation arrest (0.39 +/- 0.19) and Sertoli cell-only syndrome (0.13 +/- 0.08) were lower than that with hypospermatogenesis (1.60 +/- 1.32) and normal spermatogenesis (1.30 +/- 1.41).


CONCLUSIONS
Ad4bp/SF-1 is important for the maintenance of steroidogenesis in the human testis. DAX-1 plays a critical role in spermatogenesis in the human testis, and Sertoli cell-only syndrome and maturation arrest may result from abnormal Sertoli cell function that disrupts the normal progression of spermatogenesis.
Kojima
Yoshiyuki
Y
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. ykojima@med.nagoya-cu.ac.jp
Sasaki
Shoichi
S
Hayashi
Yutaro
Y
Umemoto
Yukihiro
Y
Morohashi
Ken-Ichiro
K
Kohri
Kenjiro
K
D000293:Adolescent; D000328:Adult; D000818:Animals; D053713:Azoospermia / Q000097:blood* / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007985:Leydig Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism* / Q000473:pathology; D013091:Spermatogenesis / Q000235:genetics; D054339:Steroidogenic Factor 1; D013739:Testosterone / Q000097:blood; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C539965:NR0B1 protein, human; C539967:Nr0b1 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D013739:Testosterone