PINEAL-GLAND HORMONE MELATONIN BINDS AND ACTIVATES AN ORPHAN OF THE NUCLEAR RECEPTOR SUPERFAMILY

Nuclear orphan receptors are members of the superfamily of structurall y related, ligand-inducible tran scription factors for which no ligand has yet been identified. Over the past few years many nuclear orphan receptors have been cloned, but only for the retinoid X receptor (RXR) has a natural ligand (9 cis-retinoic acid) been found. Here we report the identification of melatonin as a ligand for the recently cloned o rphan receptor retinoid Z receptor beta (RZR beta). We found RZR beta expression in the rat brain nearly coincident with binding sites for t he pineal gland hormone melatonin (5-methoxy-N-acetyltryptamine). We s how here binding and activation of RZR beta by melatonin with K-d and EC(50) values in the low nanomolar range. A nuclear signaling pathway for melatonin may contribute to some of the diverse and profound effec ts of this hormone, for example, in the context of circadian rhythmici ty.