Melatonin in Health and Disease

While some hormones are “trophic” in terms of their target tissues being primarily other endocrine cells (e.g. TSH, ACTH, gonadotrophins, etc.), most hormones are “pleiotropic” in as much as their target tissues are numerous and functionally heterogeneous. Thyroid hormones, insulin, adrenocorticoids and sex steroids are among the most obvious examples of this. The hormone of the brain’s pineal gland, melatonin (5-methoxy-N-acetyltryptamine) is another notable member of this class, with some interesting parallels to the other hormones mentioned. For example, like steroids and thyroxine, melatonin is secreted without exocytosis and crosses target cell membranes. Melatonin is an evolutionary old molecule that presumably appeared 3.0–2.5 billion years ago in photosynthetic cyanobacteria fulfilling the function of an antioxidant. Later on, melatonin became a ligand for membrane receptors to mediate actions on a variety of additional intracellular processes, including cell growth and metabolism, gene expression, cell cycles, ion gradients, and many other vital activities necessary to maintain proper health. From its earliest incarnation some 60 years ago as a melanin-concentrating molecule structurally related to serotonin, melatonin has been variously assigned attributes of an anti/pro-gonadotropic, chronobiotic, soporific, antioxidant and neuroprotective molecule.

The goal of this Research Topic is to unify and stimulate on-going research developments on the key functions of melatonin in human health and disease. While established areas, such as the evolution of melatonin functions, its role in regulating sleep and circadian rhythms, will be discussed in all of their ramifications, more frontier areas, such as immune functions, cancer, cell metabolism, neurodegenerative disease and others, will also be given critical review. It is our intent to define the known, to evaluate the novel, and ultimately to inspire unknown future research into this fascinating, ancient molecule.