Abstract.-Previous work has shown that the activity of the melatoninforming enzyme in the rat pineal gland is elevated in rats kept in continuous darkness as compared to those kept in continuous light. Information about environmental lighting reaches the pineal gland via nerves that liberate noradrenaline. Rat pineal glands in organ culture can form C14-melatonin from C14-tryptophan as follows: tryptophan -+ 5-hydroxytryptophan -+ serotonin-+ melatonin.Noradrenaline was found to stimulate the synthesis of C14-melatonin from C'4-tryptophan in rat pineals in organ culture. Other compounds related in structure to noradrenaline increase melatonin and serotonin synthesis and inhibit the formation of the deaminated product of serotonin, 5-hydroxyindole acetic acid. Cycloheximide, a compound that inhibits protein synthesis, also prevents the formation of serotonin, melatonin, and 5-hydroxyindole acetic acid from tryptophan in pineal organ culture. These observations suggest that noradrenaline liberated from sympathetic nerves stimulates the formation of melatonin either by increasing the formation of new melatonin-forming enzyme, by increasing transport of tryptophan into the pineal cell, or by inhibiting the metabolism of serotonin by the alternate deaminating pathway.The rat pineal gland contains an enzyme, hydroxyindole-O-methyltransferase, that O-methylates N-acetylserotonin to form melatonin.' The activity of this enzyme is more than twice as great among rats kept in continuous darkness as among animals maintained in continuous light.2 When the sympathetic nerves to the pineal are cut, light or darkness no longer produce changes in the activity of the melatonin-forming enzyme.3 These observations suggest that the release of a transmitter substance from the pineal sympathetic nerves is influenced by environmental lighting and that this neurotransmitter affects the activity of hydroxyindole-O-methyltransferase.Recently we have shown that the rat pineal gland in organ culture can form melatonin from its amino acid precursor, tryptophan.4 5 The use of this experimental system has made it possible to examine the factors in the sympathetic nerves that influence hydroxyindole-O-methyltransferase. In both the innervated pineal gland6 and the rat pineal grown in organ culture,' the synthesis of melatonin proceeds as follows: tryptophan -4 5-hydroxytryptophan -4 serotonin -4 N-acetylserotonin -4 melatonin. Serotonin can also be metabolized by deamination and oxidation to form 5-hydroxyindoleacetic acid (HIAA).7 544

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