ADRENERGIC SIGNALS DIRECT RHYTHMIC EXPRESSION OF TRANSCRIPTIONAL REPRESSOR CREM IN THE PINEAL-GLAND

Transcription factor CREM appears to play a key physiological and deve lopmental role within the hypothalamic-pituitary-gonadal axis. This ax is is modulated by the pineal hormone melatonin, whose production is i n turn driven by the endogenous clock. There is striking circadian flu ctuation of a novel CREM isoform, ICER, which is expressed at high lev els during the night. ICER is generated from an alternative, intronic promoter and functions as a powerful repressor of cyclic AMP-induced t ranscription. Rhythmic adrenergic signals originated by the clock dire ct ICER expression by stimulation of the cAMP signal transduction path way.