Objective: The role of estrogens and androgens in the etiology and progression of testicular germ cell cancer is poorly understood. To gain insight into the role of sex steroid action in testicular tumorigenesis, we have measured mRNAs encoding estrogen receptor β (ERβ), androgen receptor (AR), and their coregulators SNURF/RNF4, PIASx, and PIAS1 in testicular germ cell tumors.Methods: We used real-time quantitative reverse transcription-PCR assay to compare the steroid receptor and coregulator mRNA levels in 12 matched samples of testicular tumors and adjacent normal tissues (seminomas n=8, nonseminomas n=4). In addition, ERβ and SNURF/RNF4 protein immunoreactivity was analyzed from paraffin-embedded normal testis and tumor specimens.Results: ERβ mRNA levels were down-regulated by 59% in seminomas (p=0.017), and those of AR and SNURF/RNF4 mRNAs were decreased by 75% and 67%, respectively, in seminomas and teratocarcinomas compared to paired normal samples (p=0.034 for both, Wilcoxon signed rank test), whereas the PIASx and PIAS1 mRNA were unaltered. ERβ and SNURF/RNF4 were also clearly down-regulated at the protein level in testicular tumors.Conclusions: Expression of ERβ and SNURF/RNF4 was significantly lower in cancerous than in noncancerous testis tissue. Down-regulation of the ERβ and the coregulator SNURF/RNF4 genes may play a role in testicular tumorigenesis.