Melatonin, ~-acetyl-5-methoxytryptamine, is phylogenetically a very old molecule. Melatonin is known to exist in the dinoflagellate Gonyaulax polyedra, ' and it is perhaps produced by most if not all organisms in the animal kingdom. The conservation of this molecule during evolution may relate to its free radical scavenging ability.2 This recently discovered function of melatonin establishes a role for this indole in every organism, and indeed in every cell, from the most primitive members of the animal kingdom up to and including the was shown to be a hormone produced in and secreted from the mammalian pineal gland. In vertebrates melatonin's production in the pineal exhibits a circadian rhythm with highest blood levels of the hormone being present during the night.6 The circadian rhythm in melatonin production provides important time-of-day and time-of-year information' and, as a result, this hormonal cycle drives other 24-hour rhythms8 as well as seasonal cycles of reproduction, at least in photoperiodic mammal^.^ Although for years melatonin was thought to be exclusively produced in the pineal gland and to function only as a hormone which acted via membrane receptors located at a few discrete sites in mammals,'O~\" it was subsequently learned that in perhaps all vertebrates melatonin is found in a number of other cells and organs. l 2 , l 3 Its likely production outside the pineal gland was strongly reinforced by the observation that melatonin is even produced in unicellular organisms such as the dinoflagellate;' since they obviously lack a pineal gland, or for that matter any other organ, it is clear that individual pineal-unrelated cells can synthesize melatonin. The fact that melatonin is highly lipophilic made some investigators question Melatonin, when discovered slightly over 30 years

Melatonin as a free radical scavenger: implications for aging and age-related diseases.

PROBABLY no other organ in the body has suffered so long from a lack of its true functional recognition as the pineal gland. For more than two centuries the pineal was thought to be the seat of the soul or a vestigial remnant of the parietal eye. However, pineal research over the last 20 years has contributed significantly to unraveling the functional significance of this enigmatic endocrine gland. In this respect the isolation and characterization of melatonin by Lerner et al. (1) in 1958 constituted a landmark inasmuch as it was the first substance to be characterized in the pineal gland that reproduced many of the effects of pineal extracts or reversed the endocrine sequelae of pinealectomy. Today the pineal gland is recognized as an active functioning neuroendocrine organ that responds primarily to photic stimuli (and secondarily to hormonal signals originating in target tissues), exhibits circadian rhythms, and influences the metabolic activity of a host of endocrine glands.

Melatonin. A Mammalian Pineal Hormone

The nocturnal rise of melatonin in serum of humans is the result of endogenously released norepinephrine (NE) acting upon beta-adrenergic receptors of the pineal gland. As there is much interest in the possibility of there being changes in the function of beta-receptors in depressed patients, the nocturnal rise of melatonin was measured in depressives and healthy control subjects. In one study, multiple serum samples were taken between 4.30 p.m. to 7.30 a.m. in seven male depressed patients with melancholia and five healthy male control subjects. The melancholic patients had a significantly reduced nocturnal elevation of melatonin. In a separate study, serum samples were taken at 8 a.m. and 11 p.m. in melancholic depressives, non-melancholic depressives and healthy control subjects. The melancholic patients had a significantly lower concentration of melatonin at 11 p.m., but not at 9 a.m., than that measured in either the control subjects or the non-melancholic depressed patients. These results are similar to those found recently by several other groups of investigators. Further research is indicated to elucidate mechanism(s) responsible for this phenomenon.

/pdf/patterns-of-melatonin-rhythms-in-depression-1zrd03zpns.pdf

Patterns of melatonin rhythms in depression.

Measurement of 6-hydroxymelatonin in human urine and its diurnal variations.

Desmethylimipramine treatment increases melatonin production in humans

Identification of 6-hydroxymelatonin in normal human urine by gas chromatography-mass spectrometry.

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Identification of 6-hydroxymelatonin in normal human urine by gas chromatography-mass spectrometry.