Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand

Nucleic Acids Res. 1995 Feb 11;23(3):327-33. doi: 10.1093/nar/23.3.327.


Many important physiological functions are controlled by hormones via binding and activating members of the nuclear receptor superfamily. This group of structurally related transcription factors also includes a still growing number of orphan receptors for which no ligand is known so far. The identification of ligands for orphan receptors is a key to understanding their physiological role, as has been successfully shown for retinoid X receptors and the discovery of 9-cis retinoic acid as a specific ligand. We have discovered very recently that the pineal gland hormone melatonin is a specific ligand for the brain-specific nuclear receptor RZR beta. Here we report that the alpha-subtype of RZR, RZR alpha and its splicing variant ROR alpha 1, is also a nuclear receptor for melatonin with binding specificities in the low nanomolar range. In contrast to RZR beta, RZR/ROR alpha is expressed in many tissues and cells outside the brain. We found that RZR alpha and ROR alpha 1 vary in their constitutive transactivational activity and are activated to a different extent by melatonin. Furthermore, we identified a synthetic RZR-ligand, the thiazolidine dione CGP 52608. This compound is a functional analogue of melatonin at its nuclear receptor, but does not bind to the high affinity membrane receptor for melatonin. Therefore, this specific RZR-ligand may help to differentiate between nuclear and membrane signalling of melatonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding, Competitive
  • Cell Line
  • Drosophila
  • Kinetics
  • Ligands
  • Melatonin / metabolism
  • Melatonin / pharmacology*
  • Molecular Sequence Data
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cell Surface / physiology
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Receptors, Melatonin
  • Thiazoles / metabolism
  • Thiazoles / pharmacology*
  • Thiosemicarbazones / metabolism
  • Thiosemicarbazones / pharmacology*
  • Transcriptional Activation / drug effects*
  • Transfection


  • Ligands
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Melatonin
  • Thiazoles
  • Thiosemicarbazones
  • CGP 52608
  • Melatonin