Abstract

In this article, we attempt to classify a potential dimorphism of melatonin production. Thus, a new concept of “reserve or maximum capacity of melatonin synthetic function” is introduced to explain the subtle dimorphism of melatonin production in mammals. Considering ASMT/ASMTL genes in the pseudoautosomal region of sex chromosomes with high prevalence of mutation in males, as well as the sex bias of the mitochondria in which melatonin is synthesized, we hypothesize the existence of a dimorphism in melatonin production to favor females, which are assumed to possess a higher reserve capacity for melatonin synthesis than males. Under physiological conditions, this subtle dimorphism is masked by the fact that cells or tissues only need baseline melatonin production, which can be accomplished without exploiting the full potential of melatonin’s synthetic capacity. This capacity is believed to exceed the already remarkable nocturnal increase as observed within the circadian cycle. However, during aging or under stressful conditions, the reserve capacity of melatonin’s synthetic function is required to be activated to produce sufficiently high levels of melatonin for protective purposes. Females seem to possess a higher reserve/maximum capacity for producing more melatonin than males. Thus, this dimorphism of melatonin production becomes manifest and detectable under these conditions. The biological significance of the reserve/maximum capacity of melatonin’s synthetic function is to improve the recovery rate of organisms from injury, to increase resistance to pathogen infection, and even to enhance their chances of survival by maximizing melatonin production under stressful conditions. The higher reserve/maximum capacity of melatonin synthesis in females may also contribute to the dimorphism in longevity, favoring females in mammals.

Highlights

  • Melatonin, a small-molecular-weight antioxidant, is ubiquitously present among organisms, including the domains of bacteria and eukaryotes, and probably the domain of archaea [1]

  • Found that incubation with serotonin leads to melatonin production in a dose-responsive manner in mitochondria isolated from oocytes. These results provided direct evidence that mitochondria possess the capacity to synthesize melatonin

  • Suofu et al [43], by use of advanced biomolecular technology, have unambiguously proven that both serotonin N-acetyltransferase (SNAT) and ASMT are localized in the mitochondria and that melatonin is exclusively synthesized in the matrix of mitochondria

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Summary

Introduction

A small-molecular-weight antioxidant, is ubiquitously present among organisms, including the domains of bacteria and eukaryotes, and probably the domain of archaea [1]. In addition to its antioxidant activity, melatonin performs many functions, including circadian rhythm adjustment, immune-enhancement, reproductive regulation, sleep promotion, and anti-inflammatory activity in animals. All of these functions are acquired at a different stage of evolution [12]. In vertebrates, the pineal gland has evolved as a specific organ to generate melatonin as the signal of darkness, which synchronizes their physiological rhythmic activities [18]. This signal is extremely important for the reproductive activity of photoperiodic animals. We hope that this discussion will stimulate further research in this or related areas

Melatonin’s Synthetic Pathway in Animals
Sites of Melatonin Synthesis
Potential Gender Bias in the Expression of ASMT in Mammals
Potential Gender Bias of Mitochondria-Related Melatonin Synthesis
Evidence to Support the Masked Dimorphism of Melatonin Production
Discussion
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