Testosterone-induced upregulation of miRNAs in the female mouse liver.
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.
Delić
Denis
D
Division of Molecular Parasitology and Centre for Biological and Medical Research, Heinrich-Heine-University Düsseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
Grosser
Christian
C
Dkhil
Mohamed
M
Al-Quraishy
Saleh
S
Wunderlich
Frank
F
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D013739:Testosterone / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
D035683:MicroRNAs; D013739:Testosterone