Division of Molecular Parasitology and Centre for Biological and Medical Research, Heinrich-Heine-University Düsseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
Steroids. 2010 Dec;75(12):998-1004. doi: 10.1016/j.steroids.2010.06.010. Epub 2010 Jul 1.
Testosterone (T) regulates expression of protein-encoding genes directly through androgen receptor (AR) targeting androgen response element (ARE) in gene promoters or indirectly through non-genotropic mechanisms, but only limited information is available about T effects on expression of gene-regulatory non-coding miRNAs. Here, we investigate the effect of T on miRNA expression profiles in the female mouse liver using miRXplore microarrays and quantitative RT-PCR. T treatment for 3 weeks induced upregulation of the 6 miRNAs miR-22, miR-690, miR-122, let-7A, miR-30D and let-7D, reaching maximal expression at different time-points during T treatment. This upregulation was transient, i.e. it disappeared after T withdrawal for 12 weeks, and it was rather robust since it was not essentially affected by blood-stage infections with Plasmodium chabaudi malaria. In silico analysis revealed an ARE in the miR-122 promoter, while the other 5 miRNAs did not contain any ARE in their 2000bp promoters. The T-induced upregulation of the 6 miRNAs coincided with a downregulation of some of their target protein-encoding genes, the majority of which did incidentally not contain any ARE in their promoters. T treatment did not affect expression of AR and estrogen receptor beta (ERbeta), but significantly downregulated the miR-22 target genes ERalpha and aromatase. This downregulation is presumably not caused by T after its aromatase-mediated conversion to E(2) through ER, but rather by the T-induced upregulation of miR-22. Collectively, our data suggest that T can regulate expression of distinct miRNAs in vivo by both genotropic and non-genotropic mechanisms.
睾酮（T）通过雄激素受体（AR）靶向基因启动子中的雄激素反应元件（ARE）直接调节蛋白质编码基因的表达，或者通过非基因机制间接调节，但关于 T 对基因调节性非编码 miRNA 表达的影响，只有有限的信息。在这里，我们使用 miRXplore 微阵列和定量 RT-PCR 研究了 T 对雌性小鼠肝脏中 miRNA 表达谱的影响。T 处理 3 周诱导了 6 个 miRNA 的上调，包括 miR-22、miR-690、miR-122、let-7A、miR-30D 和 let-7D，在 T 处理期间的不同时间点达到最大表达。这种上调是短暂的，即 T 停药 12 周后消失，而且相当稳健，因为它基本上不受间日疟原虫疟原虫感染引起的血液期的影响。计算机分析显示 miR-122 启动子中存在一个 ARE，而其他 5 个 miRNA 在其 2000bp 启动子中没有任何 ARE。T 诱导的 6 个 miRNA 的上调与一些靶蛋白编码基因的下调同时发生，其中大多数基因的启动子中没有任何 ARE。T 处理不影响 AR 和雌激素受体β（ERβ）的表达，但显著下调了 miR-22 的靶基因 ERα和芳香酶。这种下调推测不是 T 通过其在 ER 中的芳香酶介导转化为 E（2）引起的，而是由 T 诱导的 miR-22 上调引起的。总的来说，我们的数据表明，T 可以通过基因和非基因机制在体内调节不同的 miRNA 表达。
