Retinoic acid-related Orphan Receptors (RORs) are a family of orphan nuclear receptors that are believed to play a role in numerous physiological processes, including circadian rhythm and bone metabolism. The endogenous ligand for these receptors is not yet known.

Retinoic acid-related Orphan Receptors (RORs) are a family of orphan nuclear receptors that are believed to play a role in numerous physiological processes, including circadian rhythm and bone metabolism. The endogenous ligand for these receptors is not yet known.

Three members of the ROR family have been identified: ROR , ROR and ROR . ROR shows the highest expression levels in the cerebellum and thalamus, whilst ROR is expressed in a more restricted fashion in the brain and retina. ROR isoforms are expressed in a number of tissues, with the ROR 2 isoform being exclusively expressed in a number of immune cell types.

The expression of RORs correlates with their roles in different physiological functions. For example, ROR regulates Purkinje cell gene expression, thereby influencing Purkinje cell maturation. ROR is crucial for rod development in the retina, and ROR -deficient mice exhibit postnatal retinal degeneration. Mice deficient in either ROR or ROR also exhibit abnormalities in circadian behavior.

The involvement of RORs in circadian rhythms is a consequence of their binding to ROR DNA response elements (ROREs). These elements are also bound by Rev-Erb and Rev-Erb . Cross-talk between these nuclear receptor families is particularly evident when considering the expression of Bmal1, a key circadian \'clock gene\' that contains two ROREs in its promoter. RORs upregulate Bmal1 expression whilst Rev-Erbs repress transcription. Bmal1/Clock or Bmal1/Npas2 heterodimers bind to promoters encoding Rev-Erb and ROR , enhancing their expression and thus constituting a positive feedback loop. The Bmal1/Clock complex also binds to the promoters of Period (Per) and Cryptochrome (Cry) genes, which in turn inhibit Bmal1/Clock and Bmal1/Npas2 complexes. These loops of gene expression are responsible for generating circadian rhythms.

External sources of pharmacological information for Retinoic Acid-related Orphan Receptors : IUPHAR Receptor CodeBJP Guide

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