Theretinoid X receptor (RXR)[1] is a type ofnuclear receptor that is activated by9-cis retinoic acid, which is discussed controversially to be of endogenous relevance,[2][3] and 9-cis-13,14-dihydroretinoic acid, which may be an endogenous mammalian RXR-selective agonist.[4]Bexarotene is the only specific activator of the RXRs which does not activateretinoic acid receptors.[5]
RXRheterodimerizes with multiple nuclear receptors includingCAR,FXR,LXR,PPAR,[6]PXR,RAR,TR,ER andVDR. RXRs are permissive co-receptors as only one of six alleles is needed for normal development and health.[7] Given this, it is difficult to extrapolate whether the RXR pathway has its own endogenous activity driven by 9-cis retinoic acid species or whether it merely participates in other pathways, predominantly the retinoic nuclear receptor pathway. Genomic knockout of the RXRs results in obesity resistance[8] whilebexarotene treatment causes severehypothyroidism,[9] suggesting that the RXR pathway functions at least to regulate thethyroid hormone receptor pathway.
As with othertype II nuclear receptors, the RXR heterodimer in the absence of ligand is bound to hormone response elements complexed withcorepressor protein. Binding of agonistligands to RXR results in dissociation of corepressor and recruitment ofcoactivator protein, which, in turn, promotestranscription of the downstream targetgene intomRNA and eventuallyprotein.
^Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, et al. (December 2006). "International Union of Pharmacology. LXIII. Retinoid X receptors".Pharmacological Reviews.58 (4):760–772.doi:10.1124/pr.58.4.7.PMID17132853.S2CID1476000.
^Haugen BR, Jensen DR, Sharma V, Pulawa LK, Hays WR, Krezel W, et al. (August 2004). "Retinoid X receptor gamma-deficient mice have increased skeletal muscle lipoprotein lipase activity and less weight gain when fed a high-fat diet".Endocrinology.145 (8):3679–3685.doi:10.1210/en.2003-1401.PMID15087432.
