The Biological Effects and Clinical Uses of the Pineal Hormone Melatonin

Abstract

Melatonin, the primary hormone of the pineal gland, acts as a powerful “chronobiotic,” maintaining normal circadian rhythms. In patients with sleep disorders and exogenously-generated desynchrony of circadian rhythms such as occurs in jet lag, oral administration of melatonin can provide the necessary resynchronization of those cycles, at dosages ranging from 0.3 to 8 mg. Synthesis of melatonin from the amino acid tryptophan has been shown to be decreased by exposure to magnetic fields and by the aging process. Melatonin also possesses potent free radical scavenging properties and has been recognized as exerting direct inhibition of cancer growth. Various cancer types have been shown to be responsive to oral melatonin (10 to 50 mg daily), including breast cancer, non-small-cell lung cancer, metastatic renal cell carcinoma, hepatocellular carcinoma, and brain metastases due to solid tumors. Melatonin has also been reported to lower total cholesterol and LDL levels in rats, and abnormally low melatonin levels have been theorized to be a factor in multiple sclerosis, sudden infant death syndrome, coronary heart disease, epilepsy, and postmenopausal osteoporosis. These reports, while preliminary, serve to further illustrate the wide range of potential effects exerted by melatonin. (Alt Med Rev 1996;1(2):94-102) Biosynthesis and Physiologic Role of Melatonin Synthesis of melatonin, the primary hormone of the pineal gland, displays a pronounced circadian rhythm. The production of melatonin (N-acetyl-5-methoxytryptamine) from the amino acid tryptophan (Figure 1) is primarily nocturnal and is controlled by exposure to cycles of light and dark, independent of sleep. The synthesis of melatonin is inhibited by exposure to light and stimulated during periods of darkness by way of a multi-synaptic neural pathway connecting the pineal gland to the external environment via the retina. 1 (Figure 2.) This sympathetic innervation, through the hypothalamic suprachiasmatic nuclei, upper thoracic pre-ganglionic neurons and post-ganglionic fibers from the superior cervical ganglion has been shown to be essential to normal production and circadian cycling of melatonin. Diabetic patients with autonomic neuropathy have been found to have lower 24-hour melatonin levels and a lower nocturnal melatonin peak when compared to diabetics with an intact autonomic system. 1 This is consistent with earlier findings in patients with abnormal pre-ganglionic 2 and post-ganglionic 3 sympathetic enervation, as well as those with cervical spinal cord

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@inproceedings{Birdsall2002TheBE, title={The Biological Effects and Clinical Uses of the Pineal Hormone Melatonin}, author={Timothy C. Birdsall}, year={2002} }