Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal gland

Nature. 1993 Sep 23;365(6444):314-20. doi: 10.1038/365314a0.


Transcription factor CREM appears to play a key physiological and developmental role within the hypothalamic-pituitary-gonadal axis. This axis is modulated by the pineal hormone melatonin, whose production is in turn driven by the endogenous clock. There is striking circadian fluctuation of a novel CREM isoform, ICER, which is expressed at high levels during the night. ICER is generated from an alternative, intronic promoter and functions as a powerful repressor of cyclic AMP-induced transcription. Rhythmic adrenergic signals originated by the clock direct ICER expression by stimulation of the cAMP signal transduction pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Circadian Rhythm*
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / physiology
  • Cyclic AMP Response Element Modulator
  • DNA
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation
  • Introns
  • Male
  • Melatonin / biosynthesis
  • Molecular Sequence Data
  • Norepinephrine / physiology
  • Pineal Gland / physiology*
  • Promoter Regions, Genetic
  • Rats
  • Rats, Wistar
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / genetics
  • Suprachiasmatic Nucleus
  • Sympathetic Nervous System / physiology*
  • Transcription, Genetic


  • DNA-Binding Proteins
  • Repressor Proteins
  • Cyclic AMP Response Element Modulator
  • DNA
  • Cyclic AMP
  • Melatonin
  • Norepinephrine