Table 2.

Findings for or against the hypothesis of melatonin as a ROR ligand.

Findings	References
In Support of Melatonin as a ROR Ligand
Melatonin binds and activates the nuclear receptor RZRβ.	[10]
Melatonin binds and activates RORα.	[11]
CGP 52608 (a novel synthetic ligand of RORα) is similar to melatonin in function. The binding of 2-[125I]iodomelatonin ([125I]melatonin) to purified cell nuclei in the spleen and thymus was demonstrated, and this binding of melatonin could be substituted by CGP 52608.	[11]
Melatonin and ROR have identical functions.	[5,40,48,52,54,63,64]
ROR mediates a number of melatonin functions.	[27,28,29,30,35,36,37,38,39,40]
Melatonin exerts an additional effect on the transcription of ROR target genes.	[12,30,37,61]
Co-localisation and co-immunoprecipitation of melatonin and ROR.	[14]
Melatonin functions via ROR without the mediation of membrane receptors.	[120,121]
Refute that Melatonin is a ROR Ligand
The studies claimed that melatonin bound to RORβ was not reproducible.	[6,10]
ROR functions independently of melatonin-induced signalling.	[21,23,31,32,33,34,51]
Melatonin and its metabolites exhibit no significant impact on the transcriptional activity of RORα and RORγ.	[17]
Molecular modelling indicates that melatonin and its metabolites are not high-affinity ROR ligands.	[17]
Melatonin directly binds to membrane receptors (MT1 or MT2) and further modulates ROR.	[15,16]