Ketola I, Pentikäinen V, Vaskivuo T, Ilvesmäki V, Herva R, Dunkel L, Tapanainen J S, Toppari J, Heikinheimo M
Children's Hospital, University of Helsinki, Finland.
J Clin Endocrinol Metab. 2000 Oct;85(10):3925-31. doi: 10.1210/jcem.85.10.6900.
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.
GATA-4是一种高度保守的转录因子，在调节胚胎形态发生和细胞分化中起关键作用。鉴于GATA-4在小鼠性腺发育和功能中的新作用，我们现在研究了它在人类睾丸中的作用。我们发现GATA-4从人类胎儿睾丸早期发育到成年期均有表达。在胎儿期和出生后发育过程中，这种转录因子在支持细胞中很明显。GATA-4在支持细胞中的表达在妊娠19 - 22周时达到峰值，此时胎儿促卵泡激素（FSH）循环水平较高。在睾丸间质细胞中，GATA-4在胎儿期和青春期后表达，与睾丸中雄激素合成活跃的时期一致；这表明GATA-4与类固醇生成之间存在联系。此外，胎儿生殖细胞和青春期前精原细胞表达GATA-4，青春期后这些细胞中的GATA-4表达下调。由于无法直接研究人类睾丸中GATA-4的激素调节，我们使用了患有内分泌异常或接受激素治疗患者的睾丸样本。人绒毛膜促性腺激素（hCG）治疗的隐睾症患者睾丸中GATA-4的表达与对照组无差异。在雄激素抵抗中，支持细胞和生殖细胞中GATA-4的表达较弱或完全缺失。GATA-4蛋白大量存在于支持细胞和睾丸间质细胞瘤中，表明其与体细胞来源的睾丸肿瘤发生或肿瘤进展有关。
