PT - JOURNAL ARTICLE AU - Takashi Furutani AU - Ken-ichi Takeyama AU - Masahiko Tanabe AU - Hiroshi Koutoku AU - Saya Ito AU - Nobuaki Taniguchi AU - Eriko Suzuki AU - Masafumi Kudoh AU - Masayuki Shibasaki AU - Hisataka Shikama AU - Shigeaki Kato TI - RETRACTION: Human Expanded Polyglutamine Androgen Receptor Mutants in Neurodegeneration as a Novel Ligand Target AID - 10.1124/jpet.105.087643 DP - 2005 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 545--552 VI - 315 IP - 2 4099 - http://jpet.aspetjournals.org/content/315/2/545.short 4100 - http://jpet.aspetjournals.org/content/315/2/545.full SO - J Pharmacol Exp Ther2005 Nov 01; 315 AB - Androgen receptor (AR) plays key roles in various biological events, including pathological processes such as prostate cancer, androgen-insensitive syndrome, and spinal and bulbar muscular atrophy (SBMA). SBMA is caused by mutation of the expanded polyglutamine (polyQ) stretches in the AR gene. Recently, we established a Drosophila SBMA model that expresses the expanded polyQ hAR mutant in eyes, which monitors neurodegeneration as a rough eye phenotype. In addition, we showed that androgen binding to the mutant hAR causes structural alterations, leading to the onset of neurodegeneration in the fly eyes. In the present study, we examined whether the ligand-induced neurodegeneration via the hAR mutant is coupled with the known ligand-induced transactivation function of hAR. By testing several known AR antagonists and several of their structure-related compounds, we unexpectedly found that none of the AR ligands antagonized the hAR mutant neurodegeneration function, and surprisingly, compound 4-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)-2-trifluoromethylbenzonitrile (RU56279) was more potent in inducing neurodegeneration. However, in vitro and in vivo mammalian assays showed that RU56279 exhibited the expected antagonistic activity with the same potency as those of the other compounds. Thus, these findings suggest the presence of a novel ligand-induced function of the polyQ hAR mutant in neurodegeneration that could not be prevented by known antagonists for the hAR transactivation function.