Recent findings have clarified the mechanisms regulating the night- and pineal-specific transcription of serotonin N-acetyltransferase, the rate-limiting enzyme in melatonin formation. Norepinephrine acting via β-adrenoceptors and cAMP at night, stimulates the cAMP response element binding protein, which turns on the transcription of N-acetyltransferase and inducible cAMP early repressor, the major inhibitor of N-acetyltransferase transcription. The tissue-specific gene expression within the pineal gland and retina derives, in part, from a pineal/retina-specific transcription factor, cone-rod homeobox protein, which binds to a pineal regulatory element. This regulatory element is present in promoters of pineal-selective enzymes, such as N-acetyltransferase, hydroxyindole-O-methyl transferase, and pineal night-specific ATPase.
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