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• W2045182642 abstract "We examined the biological importance of Sertoli cell androgen receptor (AR) genomic interaction, using a Cre-loxP approach to selectively disrupt the AR DNA-binding domain (AR-DBD). Sertoli cell (SC)-specific transgenic Abpa or AMH promoters targeted Cre-mediated inframe excision of mouse Ar exon-3, encoding the AR-DBD second zinc-finger (ZF2), generating SC-specific mutant ARΔZF2 lines designated Abp.SCARΔZF2 and AMH.SCARΔZF2, respectively. Both SCARΔZF2 lines produced infertile males exhibiting spermatogenic arrest, despite normal SC numbers and immunolocalized SC nuclear AR. Adult homozygous TgCre(+/+) SCARΔZF2 or double-TgCre(+/−)Abp/AMH.SCARΔZF2 males displayed equivalent small testes 30% of normal size, representing maximal Cre-loxP-disruption of Sertoli AR function. Hemizygous TgCre(+/−)vs. homozygous TgCre(+/+)Abp.SCARΔZF2 testes were larger (47% normal size) with more postmeiotic development, indicating dose-dependent Cre-mediated disruption of SC-specific AR-DBD activity. SCARΔZF2 males exhibited adult Leydig cell hypertrophy but normal serum testosterone levels. Sertoli cell-specific Rhox5 and Spinlw1 transcription, regulated by divergent or classical androgen-response elements, respectively, were both decreased in postnatal SCARΔZF2vs. control testes, demonstrating SC-specific AR-DBD function as early as postnatal d 5. However, Rhox5 expression declined dose-dependently, whereas Spinlw1 expression increased, in adult TgCre(+/−) and TgCre(+/+) SCARΔZF2 testes, revealing differential temporal control for distinct AR-regulated transcripts. Androgen-repressed Ngfr was not up-regulated in SCARΔZF2 testes, suggesting maintenance of a nonclassical mechanism independent of AR-DBD. Thus, our unique SCARΔZF2 paradigm provided dose-dependent Cre-mediated disruption of testicular development and gene expression revealing that the AR-DBD is essential for SC function and postmeiotic spermatogenesis. Nongenomic or AR-DBD-independent pathways appear secondary or play no major independent role in SC function." @default.
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• W2045182642 date "2009-07-02" @default.
• W2045182642 modified "2023-10-02" @default.
• W2045182642 title "Sertoli Cell Androgen Receptor DNA Binding Domain Is Essential for the Completion of Spermatogenesis" @default.
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• W2045182642 doi "https://doi.org/10.1210/en.2009-0416" @default.
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