AR3 messenger ribonucleic acid expression and its functional implication in human primary testicular failure.

ABSTRACT

AR3, a major one of androgen receptor (AR) splice variants, has been shown to play a pivotal role in concert with AR signalling in prostate cancer. The present study was undertaken to characterise the expression pattern of AR3 in normal and impaired spermatogenesis. Expression of AR3 mRNA showed significantly lower level in testicular tissues with impaired spermatogenesis when compared to normal tissues. This aberrant expression profile of AR3 in human pathological testes was further confirmed by immunoblotting analysis. Moreover, in situ hybridisation studies revealed that the transcripts of the gene were dominantly localised in the pachytene spermatocytes and round spermatids, suggesting a potential involvement of this transcriptional regulator in the auto-/paracrine regulation of meiotic and post-meiotic differentiation. This hypothesis was strengthened by the observation that AR3 mRNA expression was positively correlated to average seminiferous tubule score and was negatively correlated to serum FSH level. To the best of our knowledge, such a distinct expression profile of AR3 has not been reported previously in human testis. Overall, our data are suggestive of a novel site of action of AR3 during human spermatogenesis and should shed light on the complicated circuit composed of AR and its splice variants.