Nyctohemeral Rhythm in the Levels of S‐Adenosylmethionine in the Rat Pineal Gland and Its Relationship to Melatonin Biosynthesis

Abstract: Liquid chromatographic techniques that permit the simultaneous analysis of S‐adenosylmethionine, melatonin, and its intermediary metabolites N‐acetyl‐5‐hydroxytryptamine and 5‐hydroxytryptamine within individual pineal glands have been developed. S‐Adenosylmethionine has been shown to undergo a marked nyctohemeral rhythm in the pineal gland of the rat, with maximal levels occurring during the light period and minimal levels during the dark period. Detailed studies of the temporal relationships between the levels of S‐adenosylmethionine and those of melatonin and its intermediary metabolites suggest that an association exists between the levels of S‐adenosylmethionine and the status of the biosynthesis of melatonin. Exposure of animals to continuous light and the administration of the β‐adrenoreceptor antagonist propranolol were both found to inhibit the induction of melatonin synthesis and prevent the reduction in the levels of S‐adenosylmethionine during the dark period. As a corollary the induction of melatonin biosynthesis following the administration of the β‐adrenoreceptor agonist isoproterenol during the light period was accompanied by a marked decrease in the levels of S‐adenosylmethionine in the pineal gland. The significance of the link between the nyctohemeral rhythms in the levels of S‐adenosylmethionine and the biosynthesis of melatonin in the pineal gland is discussed in the context of the therapeutic efficacy of S‐adenosylmethionine as an antidepressant.