Hannema Sabine E, Print Cristin G, Charnock-Jones D Stephen, Coleman Nick, Hughes Ieuan A
Department of Paediatrics, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Horm Res. 2006;65(4):200-9. doi: 10.1159/000092408. Epub 2006 Mar 28.
Wolffian ducts (WDs) are the embryonic precursors of the male reproductive tract. Their development is induced by testosterone, which interacts with the androgen receptor (AR). The molecular pathways underlying androgen-dependent WD development are largely unknown. We aimed to identify AR target genes important in this process.
RNA was isolated from rat WDs at E17.5 and E20.5. Affymetrix GeneChip expression arrays were used to identify transcripts up- or downregulated more than 2-fold. Regulation of seven transcripts was confirmed using quantitative PCR.
Transcripts from 76 known genes were regulated, including modulators of insulin-like growth factor and transforming growth factor-beta signalling. By controlling these modulators, androgens may indirectly affect growth factor signalling pathways important in epithelial-mesenchymal interactions and organ development. Caveolin-1, also upregulated, may play a role in modifying as well as mediating AR signalling. Differentiation of WD epithelium and smooth muscle, innervation and extracellular matrix synthesis were reflected in regulation of other transcripts. Several genes were previously suggested to be regulated by androgens or contained functional or putative androgen/glucocorticoid response elements, indicating they may be direct targets of androgen signalling.
Our results suggest novel cohorts of signals that may contribute to androgen-dependent WD development and provide hypotheses that can be tested by future studies.
中肾管（WDs）是男性生殖道的胚胎前体。它们的发育由睾酮诱导，睾酮与雄激素受体（AR）相互作用。雄激素依赖性中肾管发育的分子途径在很大程度上尚不清楚。我们旨在鉴定在此过程中重要的AR靶基因。
在胚胎第17.5天和第20.5天从大鼠中肾管分离RNA。使用Affymetrix基因芯片表达阵列鉴定上调或下调超过2倍的转录本。使用定量PCR确认了7个转录本的调控。
76个已知基因的转录本受到调控，包括胰岛素样生长因子和转化生长因子-β信号通路的调节因子。通过控制这些调节因子，雄激素可能间接影响上皮-间充质相互作用和器官发育中重要的生长因子信号通路。同样上调的小窝蛋白-1可能在修饰以及介导AR信号中发挥作用。中肾管上皮和平滑肌的分化、神经支配和细胞外基质合成反映在其他转录本的调控中。先前有几个基因被认为受雄激素调控或含有功能性或推定的雄激素/糖皮质激素反应元件，表明它们可能是雄激素信号的直接靶标。
我们的结果提示了可能有助于雄激素依赖性中肾管发育的新信号组，并提供了可由未来研究检验的假设。
