ANTIOXIDANT PROPERTIES OF MELATONIN - AN EMERGING MYSTERY

Over three centuries ago, the French philosopher Rene Descartes descri bed the pineal gland as ''the seat of the soul.'' However, it was not until the late 1950s that the chemical identity and biosynthesis of me latonin, the principal hormone secreted by the pineal body, were revea led. Melatonin, named from the Creek melanos, meaning black, and tones , meaning color, is a biogenic amine with structural similarities to s erotonin. The mechanisms mediating the synthesis of melatonin are tran scriptionally regulated by the photoperiodic environment. Once synthes ized, the neurohormone is a biologic modulator of mood, sleep, sexual behavior, reproductive alterations, immunologic function, and circadia n rhythms. Moreover, melatonin exerts its regulatory roles through hig h-affinity, pertussis toxin-sensitive, G-protein (or guanine nucleotid e binding protein) coupled receptors that reside primarily in the eye, kidney, gastrointestinal tract, blood vessels, and brain. Additional evidence also indicates a role for melatonin in aging and age-related diseases, probably related to its efficient free radical scavenger (or antioxidant) activity. The potential clinical benefit of melatonin as an antioxidant is remarkable, suggesting that it may be of use in the treatment of many pathophysiological disease states including various cancers, hypertension, pulmonary diseases, and a variety of neurodege nerative diseases such as Alzheimer's disease. This review summarizes the biosynthesis of melatonin and its many endocrine and physiological functions, including its therapeutic potential in human disease state s. Emphasis is placed on the recent speculations indicating that this pineal hormone serves as an endogenous antioxidant agent with proficie nt free radical scavenging activity. BIOCHEM PHARMACOL 56;10:1265-1272 , 1998. (C) 1998 Elsevier Science Inc.