Melatonin: Some Aspects of Biochemistry, Physiology, and Pharmacology

Melatonin is a hormone synthesized by the pineal gland from tryptophan as a precursor and serotonin as an intermediate. It is secreted during the night and displays a peak around 3 a.m., depending on the individual chronotype. This rhythm is generated by an endogenous biological clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus and entrained to the light/dark cycle (circadian rhythm). The roles of melatonin are numerous, but this hormone is described as a messenger of nighttime to the body, a modulator of circadian rhythmicity in mammals (including humans), and a regulator of seasonal rhythms in photoperiodic animals. Melatonin, as a hormone message controlled by the central circadian clock, distributes temporal cues to the complex network of peripheral circadian clocks found in a multitude of target structures. This message favors the adaptation of the entire organism to the photoperiod. In this way, melatonin plays the role of an endogenous synchronizer capable of reinforcing the circadian rhythms, stabilizing them and maintaining their phase relationships (internal synchronization), which contributes to a physiological coherence. In fact, melatonin is not the sleep hormone, but it reinforces the contrast between day/night and activity/sleep. Further, exogenous administration of melatonin favors sleep onset (soporific effect) and influences the endogenous melatonin rhythm (advancing or delaying it according to the time of administration; a so-called chronobiotic activity) via the circadian clock. This chronobiotic activity is the pharmacological basis for the treatment of dysrhythmia (jet lag syndrome, delayed-sleep phase syndrome, non-24 circadian sleep disorder in blind people, etc.).