机构：[1]George Whipple Laboratory for Cancer Research , Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center,University of Rochester Medical Center, Rochester, New York 14646[2]Department of Urology, the Second Affiliated Hospital of Suzhou University, Suzhou, 215004 China[3]Chawnshang Chang Liver Cancer Center and Department of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016 China[4]Sex Hormone Research Center, China Medical University/Hospital, Taichung, 404 Taiwan
Testicular nuclear receptor 4 (TR4), also known as NR2C2, belongs to the nuclear receptor superfamily and shares high homology with the testicular nuclear receptor 2. The natural ligands of TR4 remained unclear until the recent discoveries of several energy/lipid sensors including the polyunsaturated fatty acid metabolites, 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid, and their synthetic ligands, thiazolidinediones, used for treatment of diabetes. TR4 is widely expressed throughout the body and particularly concentrated in the testis, prostate, cerebellum, and hippocampus. It has been shown to play important roles in cerebellar development, forebrain myelination, folliculogenesis, gluconeogenesis, lipogenesis, muscle development, bone development, and prostate cancer progression. Here we provide a comprehensive summary of TR4 signaling including its upstream ligands/activators/suppressors, transcriptional coactivators/repressors, downstream targets, and their in vivo functions with potential impacts on TR4-related diseases. Importantly, TR4 shares similar ligands/activators with another key nuclear receptor, peroxisome proliferator-activated receptor gamma, which raised several interesting questions about how these 2 nuclear receptors may collaborate with or counteract each other's function in their related diseases. Clear dissection of such molecular mechanisms and their differential roles in various diseases may help researchers to design new potential drugs with better efficacy and fewer side effects to battle TR4 and peroxisome proliferator-activated receptor gamma involved diseases.
基金：
This work was supported by the National Institutes of
Health (Grants CA156700 and DK73414), the George Whipple
Professorship Endowment; and the Taiwan Department of
Health Clinical Trial, Research Center of Excellence (Grant
DOH99-TD-B-111-004 to China Medical University, Taichung,
Taiwan).
第一作者机构：[1]George Whipple Laboratory for Cancer Research , Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center,University of Rochester Medical Center, Rochester, New York 14646
通讯作者：
通讯机构：[1]George Whipple Laboratory for Cancer Research , Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center,University of Rochester Medical Center, Rochester, New York 14646[3]Chawnshang Chang Liver Cancer Center and Department of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016 China[4]Sex Hormone Research Center, China Medical University/Hospital, Taichung, 404 Taiwan
推荐引用方式(GB/T 7714)：
Shin-Jen Lin,Yanqing Zhang,Ning-Chun Liu,et al.Minireview: Pathophysiological Roles of the TR4 Nuclear Receptor: Lessons Learned From Mice Lacking TR4[J].MOLECULAR ENDOCRINOLOGY.2014,28(6):805-21.doi:10.1210/me.2013-1422.
APA：
Shin-Jen Lin,Yanqing Zhang,Ning-Chun Liu,Dong-Rong Yang,Gonghui Li&Chawnshang Chang.(2014).Minireview: Pathophysiological Roles of the TR4 Nuclear Receptor: Lessons Learned From Mice Lacking TR4.MOLECULAR ENDOCRINOLOGY,28,(6)
MLA：
Shin-Jen Lin,et al."Minireview: Pathophysiological Roles of the TR4 Nuclear Receptor: Lessons Learned From Mice Lacking TR4".MOLECULAR ENDOCRINOLOGY 28..6(2014):805-21
