Transcriptional profiling of Androgen Receptor (AR) mutants suggests instructive and permissive roles of AR signaling in germ cell development

摘要: The androgen receptor (AR) is a transcription factor that plays critical role in male sexual development, spermatogenesis, and maintenance of hormonal homeostasis. Despite the extensive knowledge phenotypic consequences mutations Ar, very little known about transcriptional targets AR within testis. To identify potential signaling testis, we have analyzed profile adult testes from Ar hypomorphs alone or combination with Sertoli cell-specific ablation. Using Affymetrix MOE430A mouse genome arrays interrogated more than 22,000 transcripts. We found expression level 62 transcripts mutants differed by greater 2-fold compared wild type. also were up-regulated down-regulated, highlighting AR's as repressor Twelve uniquely affected, 16 severely affected ablation hypomorphic mutants. comparative genomic approach, 6 kb around start sites for conserved AREs (androgen response elements). identified at least one ARE 65% genes misregulated our microarray analysis where clear mouse-human orthologs available. used reporter assay cell culture to functionally verify kallikrein 27 gene. This suggests majority high probability being direct targets. these encode diverse array proteins whose molecular functions support contention supports spermatogenesis both permissive instructive fashion.