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2014 ; 28
(6
): 805-21
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Minireview: Pathophysiological roles of the TR4 nuclear receptor: lessons learned
from mice lacking TR4
#MMPMID24702179
Lin SJ
; Zhang Y
; Liu NC
; Yang DR
; Li G
; Chang C
Mol Endocrinol
2014[Jun]; 28
(6
): 805-21
PMID24702179
show ga
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 ?, 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 ? involved diseases.