Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily.
Nuclear orpan receptors are members of the superfamily of structurally related, ligand-inducible transcription 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 orphan receptor retinoid Z receptor beta (RZR beta). We found RZR beta expression in the rat brain nearly coincident with binding sites for the pineal gland hormone melatonin (5-methoxy-N-acetyltryptamine). We show here binding and activation of RZR beta by melatonin with Kd and EC50 values in the low nanomolar range. A nuclear signaling pathway for melatonin may contribute to some of the diverse and profound effects of this hormone, for example, in the context of circadian rhythmicity.
Becker-André
M
M
Glaxo Institute for Molecular Biology, Plán-les-Ouates, Switzerland.
Wiesenberg
I
I
Schaeren-Wiemers
N
N
André
E
E
Missbach
M
M
Saurat
J H
JH
Carlberg
C
C
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D017931:DNA Primers; D004330:Drosophila; D006367:HeLa Cells; D006801:Humans; D008550:Melatonin / Q000378:metabolism*; D008969:Molecular Sequence Data; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D010870:Pineal Gland / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D044094:Receptors, Melatonin; D018168:Receptors, Retinoic Acid; D015533:Transcriptional Activation
D017931:DNA Primers; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D018168:Receptors, Retinoic Acid; D008550:Melatonin