Chronobiological Effects of L-Tryptophan in Humans: Influence on Melatonin Secretion

Abstract

Melatonin synthesis in the pineal organ results from acetylation of serotonin (5-HT) by arylalkylamine-N-acetyltransferase (NAT) and subsequent conversion of N-acetylserotonin to melatonin by hydroxyindole-O-methyltrans-ferase. A substantial amount of data derived from animal experiments indicates that the circadian rhythm of melatonin synthesis with an about tenfold increase in the dark phase is closely associated with the oscillation in the activity of pineal NAT, the rate-limiting enzyme of melatonin production. The major biological event controlling NAT and thus melatonin synthesis is the β-adrenoreceptor-linked increase in pineal cAMP production. However, the precise mechanism by which the noradrenergie (NE) input from sympathetic nerve endings controls the circadian melatonin rhythm is a matter of debate (circadian changes in NE input, β-adrenoreceptor density, uncoupling of the receptor after agonist interaction, synergism with α₁-adrenoreceptors, etc.; for summary, see Klein et al., 1987; Cardinali et al., 1987; Gonzalez-Brito and Reiter, 1987). In addition to the predominant role of mechanisms controlling NAT activity, many data are compatible with the suggestion that the availability of serotonin may be involved in regulating melatonin synthesis (Wurtman and Ozaki, 1978; Chan and Ebadi, 1981; for summary, see Ebadi, 1984). Recently, Demisch et al. (1986, 1987) reported that the administration of the selective 5-HT reuptake inhibitor fluvoxamine at night led to significant increases of nocturnal melatonin concentrations in the plasma of healthy volunteers and a delayed decline of plasma melatonin in early morning hours. This observation led to the hypothesis that the availability of serotonin as a substrate of NAT may be of relevance in the process of terminating the synthesis of melatonin. This study was designed to examine this hypothesis by elucidating the influence of L-tryptophan on melatonin plasma levels in healthy subjects.