Expression of transcription factor GATA-4 during human testicular development and disease.
GATA-4 is a highly conserved transcription factor that plays a critical role in regulating embryonic morphogenesis and cellular differentiation. Given the emerging role of GATA-4 in the development and function of murine gonads, we have now studied its role in human testis. We find that GATA-4 is expressed from early human fetal testicular development to adulthood. This transcription factor is evident in Sertoli cells through fetal and postnatal development. Expression of GATA-4 in Sertoli cells peaks at 19-22 weeks gestation at the time of high circulating fetal FSH. In Leydig cells, GATA-4 is expressed during fetal period and after puberty, coinciding with the periods of active androgen synthesis in the testis; this suggests a link between GATA-4 and steroidogenesis. Also, fetal germ cells and prepubertal spermatogonia express GATA-4, and it is down-regulated in these cells after puberty. As hormonal regulation of GATA-4 in human testis was not possible to study directly, we used testicular samples from patients who had endocrine abnormalities or were hormonally treated. Testicular expression of GATA-4 in hCG-treated cryptorchidism does not differ from that in controls. In androgen resistance, GATA-4 expression in Sertoli and germ cells is weak or totally absent. GATA-4 protein is abundantly present in Sertoli and Leydig cell tumors, suggesting a relationship to tumorigenesis or tumor progression in somatic cell-derived testicular neoplasms.
Ketola
I
I
Children's Hospital, University of Helsinki, Finland.
Pentikäinen
V
V
Vaskivuo
T
T
Ilvesmäki
V
V
Herva
R
R
Dunkel
L
L
Tapanainen
J S
JS
Toppari
J
J
Heikinheimo
M
M
D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003456:Cryptorchidism / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D050991:GATA4 Transcription Factor; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018310:Sertoli-Leydig Cell Tumor / Q000235:genetics / Q000378:metabolism; D013733:Testicular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D000726:Androgen Antagonists; D006063:Chorionic Gonadotropin; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D014157:Transcription Factors; D007987:Gonadotropin-Releasing Hormone