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.
Glaxo Institute for Molecular Biology, Plán-les-Ouates, Switzerland.
M
M
Becker-André
I
I
Wiesenberg
N
N
Schaeren-Wiemers
E
E
André
M
M
Missbach
J H
JH
Saurat
C
C
Carlberg
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