Melatonin as the Cornerstone of Neuroimmunoendocrinology

Abstract

Much attention has been recently drawn to studying melatonin - a hormone whose synthesis was first found in the epiphysis (pineal gland). This interest can be due to discovering the role of melatonin in numerous physiological processes. It was the discovery of melatonin synthesis in endocrine organs (pineal gland), neural structures (Purkinje cells in the cerebellum, retinal photoreceptors), and immunocompetent cells (T lymphocytes, NK cells, mast cells) that triggered the evolution of new approaches to the unifield signal regulation of homeostasis, which, at the turn of the 21st century, lead to the creation of a new integral biomedical discipline - neuroimmunoendocrinology. While numerous hormones have been verified over the last decade outside the "classical" locations of their formation, melatonin occupies an exclusive position with regard to the diversity of locations where it is synthesized and secreted. This review provides an overview and discussion of the major data regarding the role of melatonin in various physiological and pathological processes, which affords grounds for considering melatonin as the "cornerstone" on which neuroimmunoendocrinology has been built as an integral concept of homeostasis regulation.

Keywords: anti-inflammatory function; antioxidant activity; homeostasis; melatonin; neuroimmunoendocrinology.

Figure 1

Melatonin localization in the human body. The figure illustrates the unique property of melatonin to have the most widespread localization in the human body, being synthesized in various organs.

Figure 2

Melatonin is the main regulator of the circadian rhythm in all living organisms. Light information from the rods and cones of the retina through the ganglion cells and directly from the light-sensitive ganglion cells enters the paired suprachiasmatic nucleus (SCN) of the hypothalamus. These signals then travel to the cervical spinal cord, from where they travel back to the brain and reach the pineal gland. During sleep in the dark, when most of the SCN neurons are inactive, the nerve endings release norepinephrine, which activates the synthesis of melatonin in the pinealocytes. Bright light blocks the synthesis, while in constant darkness, the rhythmic production, maintained by the periodic activity of the SCN, is preserved.

Figure 3

Diagram of the biological role of melatonin.

Figure 4

Melatonin and mitochondrial function. The high concentration of melatonin in mitochondria is due to the fact that PEPT1/2 proteins present in the mitochondrial membrane move melatonin into mitochondria against the gradient. Since melatonin is a powerful free radical scavenger, its presence in mitochondria reflects the participation of this hormone in compensatory reactions that occur during the development of mitochondrial aging and pathology associated with mitochondrial dysfunction ([133], modified).