Melatonin and Biological Rhythms: from bench to bedside

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Background

Melatonin is a multifaceted hormone. Its outstanding role as an internal temporal marker, signaling to the organism the daily and seasonal variations in the environmental light/dark cycle, grants melatonin a core function in physiologic regulation. Immediate and late actions involved in multiple metabolic functions, autonomic control, oxidative stress, gene transcription, and even fetal programming have also been described.
The peculiarity of melatonin action is related to its timed secretion regulated by the endogenous timekeeping system, so that circulating melatonin is restricted to the dark night in all species. The endogenous timekeeping system is a widespread network organized in several levels, from the molecular one to the neuroendocrine system, having the suprachiasmatic nuclei of the hypothalamus as its core. In this way, melatonin is not just regulated by this system, but it is also part of it, regulating a number of biological rhythms. Although a large amount of data on the functions of melatonin has been incorporated with experiments in different species, the translation of these results to human physiology and health still needs to be further investigated.

As a chronobiotic agent melatonin is able to synchronize and reset biological oscillations. The potential of melatonin to promote entrainment of rest/activity circadian rhythms has been largely demonstrated in mammals. In humans, it is recommended for therapeutic use in circadian rhythm disorders such as phase delayed syndrome and non-24 hours circadian rhythm disorder. Other conditions such as autistic spectrum disorder, neurogenetic and psychiatric diseases have been included in the therapeutic range, as well as syndromes involving melatonin disfunction. Transgenerational effects have been described in rats and are related to the daily maternal melatonin rhythm, which typically increases in amplitude towards the end of gestation. Transplacental melatonin has several programming effects on the fetus including the timing of the newborn future physiology and behavior.
However, studies in humans usually focus on sleep parameters, disregarding the aforementioned broad action profile of melatonin. Pinealectomy and melatonin replacement experiments in mammals have revealed their role in regulating daily and seasonal energy expenditure, including actions on insulin sensitivity and glucose tolerance, body weight, and adipose tissue. Also, insights into autonomic control and blood pressure daily rhythm have emerged from these experiments and have been recently translated into studies in humans. Incorporating this impressive amount of results into clinical practice is a challenge for researchers.

The aim of the current Research Topic is to explore the multiple faces of melatonin mediated by its timed mechanism of action in laboratory and translational studies. We welcome original research papers and review articles that focus on, but are not limited to, the following topics:

- Endogenous timekeeping system and mechanisms of melatonin action in its different levels, from molecular to the neuroendocrine system organization.

- Melatonin effects in various aspects of the timed regulation of physiological mechanisms, including but not restricted to, the sleep/wake cycle, energy metabolism, autonomic control, inflammation, and oxidative stress.

- Therapeutic use of melatonin as a chronobiotic agent and description of syndromes involving biological rhythms disfunction.

- Role of melatonin in fetal programming and transgenerational effects.

Keywords: Melatonin, Sleep, Circadian, Rhythm, Metabolism, Autonomic control, Inflammation, Oxidative stress

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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