Influence of testosterone and a novel SARM on gene expression in whole blood of Macaca fascicularis.
Anabolic hormones, including testosterone, have been suggested as a therapy for aging-related conditions, such as osteoporosis and sarcopenia. These therapies are sometimes associated with severe androgenic side effects. A promising alternative to testosterone replacement therapy are selective androgen receptor modulators (SARMs). SARMs have the potential to mimic the desirable central and peripheral androgenic anabolic effects of testosterone without having its side effects. In this study we evaluated the effects of LGD2941, in comparison to testosterone, on mRNA expression of selected target genes in whole blood in an non-human model. The regulated genes can act as potential blood biomarker candidates in future studies with AR ligands. Cynomolgus monkeys (Macaca fascicularis) were treated either with testosterone or LGD2941 for 90 days in order to compare their effects on mRNA expression in blood. Blood samples were taken before SARM application, on day 16 and on day 90 of treatment. Gene expression of 37 candidate genes was measured using quantitative real-time RT-PCR (qRT-PCR) technology. Our study shows that both testosterone and LGD2941 influence mRNA expression of 6 selected genes out of 37 in whole blood. The apoptosis regulators CD30L, Fas, TNFR1 and TNFR2 and the interleukins IL-12B and IL-15 showed significant changes in gene expression between control and the treatment groups and represent potential biomarkers for androgen receptor ligands in whole blood.
Physiology Weihenstephan, Technische Universität München, Weihenstephaner Berg 3, Freising, Germany. irmgard.riedmaier@wzw.tum.de
Irmgard
I
Riedmaier
Ales
A
Tichopad
Martina
M
Reiter
Michael W
MW
Pfaffl
Heinrich H D
HH
Meyer
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007378:Interleukins / Q000235:genetics; D008252:Macaca fascicularis / Q000097:blood / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D012333:RNA, Messenger / Q000097:blood; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology*
C524268:6-(2-methyl-5-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-4-trifluoromethylquinolin-2(1H)-one; D051017:Apoptosis Regulatory Proteins; D007378:Interleukins; D011759:Pyrrolidines; D015363:Quinolones; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D013739:Testosterone