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Review
. 2023 Jan 6;12(1):89.
doi: 10.3390/biology12010089.

Melatonin: Both a Messenger of Darkness and a Participant in the Cellular Actions of Non-Visible Solar Radiation of Near Infrared Light

Dun-Xian Tan  1 , Russel J Reiter  1 , Scott Zimmerman  2 , Ruediger Hardeland  3
Affiliations
Review

Melatonin: Both a Messenger of Darkness and a Participant in the Cellular Actions of Non-Visible Solar Radiation of Near Infrared Light

Dun-Xian Tan et al. Biology (Basel). .

Abstract

Throughout the history of melatonin research, almost exclusive focus has been on nocturnally-generated pineal melatonin production, which accounts for its circadian rhythm in the blood and cerebrospinal fluid; these light/dark melatonin cycles drive the daily and seasonal photoperiodic alterations in organismal physiology. Because pineal melatonin is produced and secreted primarily at night, it is referred to as the chemical expression of darkness. The importance of the other sources of melatonin has almost been ignored. Based on current evidence, there are at least four sources of melatonin in vertebrates that contribute to the whole-body melatonin pool. These include melatonin produced by (1) the pineal gland; (2) extrapineal cells, tissues, and organs; (3) the microbiota of the skin, mouth, nose, digestive tract, and vagina as well as (4) melatonin present in the diet. These multiple sources of melatonin exhibit differentially regulated mechanisms for its synthesis. Visible light striking the retina or an intense physical stimulus can suppress nocturnal pineal melatonin levels; in contrast, there are examples where extrapineal melatonin levels are increased during heavy exercise in daylight, which contains the whole range of NIR radiation. The cumulative impact of all cells producing augmented extrapineal melatonin is sufficient to elevate sweat concentrations, and potentially, if the exposure is sustained, to also increasing the circulating values. The transient increases in sweat and plasma melatonin support the premise that extrapineal melatonin has a production capacity that exceeds by far what can be produced by the pineal gland, and is used to maintain intercellular homeostasis and responds to rapid changes in ROS density. The potential regulatory mechanisms of near infrared light (NIR) on melatonin synthesis are discussed in detail herein. Combined with the discovery of high levels of melanopsin in most fat cells and their response to light further calls into question pineal centric theories. While the regulatory processes related to microbiota-derived melatonin are currently unknown, there does seem to be crosstalk between melatonin derived from the host and that originating from microbiota.

Keywords: cerebrospinal fluid; circadian rhythm; light; melatonin synthesis; microbiota; mitochondria; near-infrared radiation; pineal gland.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The classic melatonin biosynthetic pathway in microorganisms and animals. Melatonin synthesis occurs primarily in the mitochondria of the cells. TPH: tryptophan hydroxylase, AADC: aromatic amino acid decarboxylase, SNAT (AANAT): aralkylamine N-acetyltransferase, ASMT (HIOMT): N-acetylserotonin O-methyltransferase (hydroxyindole-O-methyltransferase), SAM: S-adenosyl methionine, SHA: S-adenosyl homocysteine.
Figure 2
Figure 2
The differentially regulated melatonin synthetic pathway in cytosol, mitochondria, and microbiota. In the pineal, NE, which represents the dark message, acts on the Aβ and Aα membrane receptors to activate the tmAC to generate cytosolic cAMP, which is mitochondria impermeable. NIR is associated with sun exposure and acts mainly on the mitochondrial sAC to increase the mitochondrial cAMP, which in situ phosphorylates the AANTT at the posttranslational level. This model assumed an activation of sAC by NO, which would require further confirmation. In addition, NO activates sGC to increase cGMP, which can inhibit the phosphodiesterase to reduce cAMP degradation and further increases the mitochondria cAMP content. The posttranslational regulation of AANAT activity quickly increases the melatonin synthesis, as seen in extrapineal cells. The regulatory mechanisms of melatonin synthesis in microbiota are currently unknown, but it is hypothesized there is a reciprocal effect between the melatonin produced by the host and microbiota. NE: norepinephrine, Aβ: β adrenergic receptor, Aα: α adrenergic receptor, Gs: stimulatory G protein, Gq: G protein q subunit, tmAC: transmembrane adenylyl cyclase, sAC: soluble adenylyl cyclase, sGC: soluble Guanyl cyclase, PPD: phosphodiesterase, PLC: phospholipase C, PKC: protein kinase C, PKA: protein kinase A, AANAT: arylalkylamine acetyltransferase, pAANAT: phosphorylated AANAT, NO: nitric oxide, CCO: cytochrome C oxidase (mitochondrial complex IV), 14-3-3: 14-3-3 protein, Mel: melatonin.
Figure 3
Figure 3
The plasma melatonin levels as a function of time during heavy exercise under sunlight and circadian time. During a 4-h intense exercise session, plasma melatonin levels rose to 200 pg/mL in 20 min followed by a plateau for the duration of the exercise (five test subjects with indwelling catheter measured plasma melatonin at 10, 20, 30, 40, 50, 60, 240, and 300 min, respectively). This figure was from [159] and permitted by the authors.
Figure 4
Figure 4
Illustration of the melatonin pool of vertebrates. NIR: near infrared radiation.
See this image and copyright information in PMC

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