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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 10 3925-3931
Copyright © 2000 by The Endocrine Society

Original Studies

Expression of Transcription Factor GATA-4 during Human Testicular Development and Disease1

Ilkka Ketola, Virve Pentikäinen, Tommi Vaskivuo, Vesa Ilvesmäki, Riitta Herva, Leo Dunkel, Juha S. Tapanainen, Jorma Toppari and Markku Heikinheimo

Children’s Hospital (I.K., V.P., L.D., M.H.), Department of Medicine (V.I.), University of Helsinki, 00290 Helsinki, Finland; Departments of Physiology and Pediatrics, University of Turku (J.T.), 20520 Turku, Finland; Departments of Obstetrics and Gynecology (T.V., J.S.T.) and Pathology (R.H.), University of Oulu, 90220 Oulu, Finland; and Department of Pediatrics, Washington University (M.H.), St. Louis, Missouri 63110

Address all correspondence and requests for reprints to: Markku Heikinheimo, M.D., Ph.D., Children’s Hospital, Stenbäckinkatu 11, 00290 Helsinki, Finland. E-mail: markku.heikinheimo{at}helsinki.fi

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.




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