Exercise and melatonin in humans: reciprocal benefits (original) (raw)

Structure and function of the human circadian system Most organisms, from cyanobacteria to humans, display rhythms in their physiology and behavior that are synchronized to environmental cycles of 24 hr. These rhythms are known as circadian rhythms. To generate this rhythmicity, organisms are provided with a time measuring device, known as the circadian timekeeping system. In humans, the circadian system is composed of a hierarchical network of structures responsible for the generation of circadian rhythms which keep cellular clocks synchronized with the daily environmental cycles (Fig. 1), especially the photoperiod. In mammals, the main circadian pacemaker is located in the suprachiasmatic nuclei (SCN) of the hypothalamus where each individual neuron can independently generate a self-sustained circadian rhythm. These rhythms are generated by a molecular clock based on complex cycles of transcription, translation, protein-protein interaction, phosphorylation, nuclear translocation, and protein degradation, all of which impose a delay to create a coordinated molecular cycle that matches the 24-hr environmental LD period [1]. The basic loop of the molecular clock is composed of two positive elements, CLOCK and BMAL1, which dimerize to activate rhythmic transcription of Per and Cry genes by binding to specific promoter elements. After translation, PER and CRY proteins dimerize and undergo nuclear translocation to inhibit the coupling of CLOCK:BMAL1, resulting in decreased transcription of Per and Cry genes. This molecular clock also regulates the expression of several clock-controlled genes (3-15%), which are not a part of the main clock machinery but are responsible for the generation of circadian rhythmicity in many physiological processes [2]. Recently, the molecular clock has been also reported in many peripheral tissues and organs such as, adipose tissue,