scholarly journals The Reserve/Maximum Capacity of Melatonin’s Synthetic Function for the Potential Dimorphism of Melatonin Production and Its Biological Significance in Mammals

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7302
Author(s):  
Dun-Xian Tan ◽  
Rüdiger Hardeland

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.

2021 ◽  
Vol 4 (1) ◽  
pp. 99-114
Author(s):  
Janaína B Garcia ◽  
Fernanda G Do Amaral ◽  
Daniela C Buonfiglio ◽  
Rafaela FA Vendrame ◽  
Patrícia L Alves ◽  
...  

The pineal gland synthesizes melatonin exclusively at night, which gives melatonin the characteristic of a temporal synchronizer of the physiological systems. Melatonin is a regulator of insulin activities centrally and also peripherally and its synthesis is reduced in diabetes.  Since monosodium glutamate (MSG) is often used to induce the type 2 diabetic and metabolic syndrome in animal models, the purpose of this work is to evaluate the potential effects of MSG given to neonates on the pineal melatonin synthesis in different aged male and female rats. Wistar rats were subcutaneously injected with MSG (4mg/g/day) or saline solution (0.9%) from the second to eighth post-natal day. The circadian profiles both melatonin levels and AANAT activity were monitored at different ages. Body weight, naso-anal length, adipose tissues weight, GTT, ITT and serum insulin levels were also evaluated. Typical obesity with the neonatal MSG treatment was observed, indicated by a great increase in adipose depots without a concurrent increase in body weight. MSG treatment did not cause hyperglycemia or glucose intolerance, but induced insulin resistance. An increase of melatonin synthesis at ZT 15 with phase advance was observed in in some animals. The AANAT activity was positively parallel to the melatonin circadian profile. It seems that MSG causes hypothalamic obesity which may increase AANAT activity and melatonin production in pineal gland. These effects were not temporally correlated with insulin resistance and hyperinsulinemia indicating the hypothalamic lesions, particularly in arcuate nucleus induced by MSG in early age, as the principal cause of the increase in melatonin production.


1988 ◽  
Vol 475 (2) ◽  
pp. 393-396 ◽  
Author(s):  
A. Gonzalez-Brito ◽  
R.J. Reiter ◽  
C. Santana ◽  
A. Menedez-Pelaez ◽  
J.M. Guerrero

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5275
Author(s):  
Jun Pan ◽  
Fengming Li ◽  
Caidie Wang ◽  
Xiaobin Li ◽  
Shiqi Zhang ◽  
...  

The purpose of this study is to investigate the potential effects of 5-hydroxytryptophan (5-HTP) duodenal perfusion on melatonin (MT) synthesis in the gastrointestinal (GI) tract of sheep. 5-hydroxytryptophan is a precursor in the melatonin synthetic pathway. The results showed that this method significantly increased melatonin production in the mucosa of all segments in GI tract including duodenum, jejunum, ileum, cecum and colon. The highest melatonin level was identified in the colon and this indicates that the microbiota located in the colon may also participate in the melatonin production. In addition, portion of the melatonin generated by the GI tract can pass the liver metabolism and enters the circulation via portal vein. The current study provides further evidence to support that GI tract is the major site for melatonin synthesis and the GI melatonin also contributes to the circulatory melatonin level since plasma melatonin concentrations in 5-HTP treated groups were significantly higher than those in the control group. In conclusion, the results show that 10–50 mg of 5-HTP flowing into the duodenum within 6 h effectively improve the production of melatonin in the GI tract and melatonin concentration in sheep blood circulation during the day.


Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 523
Author(s):  
Ok Jin Hwang ◽  
Kiyoon Kang ◽  
Kyoungwhan Back

Light is an important factor influencing melatonin synthesis in response to cadmium treatment in rice. However, the effects of light quality on, and the involvement of phytochrome light receptors in, melatonin production have not been explored. In this study, we used light-emitting diodes (LEDs) to investigate the effect of light wavelength on melatonin synthesis, and the role of phytochromes in light-dependent melatonin induction in rice. Upon cadmium treatment, peak melatonin production was observed under combined red and blue (R + B) light, followed by red (R) and blue light (B). However, both far-red (FR) LED light and dark treatment (D) failed to induce melatonin production. Similarly, rice seedlings grown under the R + B treatment showed the highest melatonin synthesis, followed by those grown under B and R. These findings were consistent with the results of our cadmium treatment experiment. To further confirm the effects of light quality on melatonin synthesis, we employed rice photoreceptor mutants lacking functional phytochrome genes. Melatonin induction was most inhibited in the phytochrome A mutant (phyA) followed by the phyB mutant under R + B treatment, whereas phyB produced the least amount of melatonin under R treatment. These results indicate that PhyB is an R light receptor. Expression analyses of genes involved in melatonin biosynthesis clearly demonstrated that tryptophan decarboxylase (TDC) played a key role in phytochrome-mediated melatonin induction when rice seedlings were challenged with cadmium.


1992 ◽  
Vol 263 (3) ◽  
pp. E481-E488
Author(s):  
A. K. Ho ◽  
C. L. Chik

In rat pinealocytes, amiloride can modulate adrenergic-stimulated cyclic nucleotide accumulation. In this study, the effect of amiloride on melatonin production was characterized. Addition of 5-(N,N-hexamethylene)amiloride, a potent inhibitor of the Na(+)-H+ antiport, dose dependently inhibited norepinephrine- and isoproterenol-stimulated N-acetyltransferase (NAT) activity and melatonin production. Similar inhibition was also observed when pineal melatonin synthesis was stimulated directly with forskolin or dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP), suggesting that the site of inhibition is distal to cAMP accumulation. Similarities between the inhibitory potencies of amiloride derivatives on the Na(+)-H+ antiport and pineal melatonin synthesis indicate that the observed inhibition on pineal melatonin synthesis by amilorides may be secondary to their actions on the Na(+)-H+ antiport. Further studies also indicate that the inhibitory effect of amilorides was not secondary to its cytotoxic actions and that amilorides had no direct antagonistic action on NAT activity. Our findings, therefore, suggest that, in addition to their effects on cyclic nucleotide accumulation, the Na(+)-H+ antiport also plays an important role in the cAMP-mediated melatonin synthesis in the rat pineal gland.


1992 ◽  
Vol 8 (5) ◽  
pp. 487-490 ◽  
Author(s):  
Gregory M. Cahill ◽  
Joseph C. Besharse

AbstractSeveral lines of evidence indicate that retinal photoreceptors produce melatonin. However, there are other potential melatonin sources in the retina, and melatonin synthesis can be regulated by feedback from the inner retina. To analyze cellular mechanisms of melatonin regulation in retinal photoreceptors, we have developed an in vitro method for destruction of the inner retina that preserves functional photoreceptors in contact with the pigment epithelium. Eyecups, which include the neural retina, retinal pigment epithelium, choroid, and sclera were prepared. The vitreal surface of the retina in each eyecup was washed sequentially with 1% Triton X-100, water, and culture medium. This lysed the ganglion cells and neurons and glia of the inner nuclear layer, causing the retina to split apart within the inner nuclear layer. The damaged inner retina was peeled away, leaving photoreceptors attached to the pigment epithelium. The cell density of the inner nuclear layer was reduced 94% by this method, but there was little apparent damage to the photoreceptors. Lesioned eyecups produced normal melatonin levels in darkness at night, and melatonin production was inhibited by light. These results indicate that the inner retina is not necessary for melatonin production nor for regulation of photoreceptor melatonin synthesis by light. The lesion method used in this study may be useful for other physiological and biochemical studies of photoreceptors.


2002 ◽  
Vol 87 (10) ◽  
pp. 4699-4706 ◽  
Author(s):  
Steven L. Coon ◽  
Elena del Olmo ◽  
W. Scott Young ◽  
David C. Klein

Arylalkylamine N-acetyltransferase (AANAT; serotonin N-acetyltransferase, EC 2.3.1.87) plays a unique transduction role in vertebrate physiology as the key interface between melatonin production and regulatory mechanisms. Circulating melatonin is elevated at night in all vertebrates, because AANAT activity increases in the pineal gland in response to signals from the circadian clock. Circadian regulation of melatonin synthesis is implicated in a variety of human problems, including jet lag, shift work, insomnia, and abnormal activity rhythms in blind persons. In this report AANAT was studied in the rhesus macaque to better understand human melatonin regulation. AANAT mRNA is abundant in the pineal gland and retina, but not elsewhere; AANAT mRNA is uniformly distributed in the pineal gland, but is limited primarily to the photoreceptor outer segments in the retina. Day and night levels of pineal and retinal AANAT mRNA are similar. In contrast, AANAT activity and protein increase more than 4-fold at night in both tissues. The activity of hydroxyindole-O-methyltransferase, the last enzyme in melatonin synthesis, is tonically high in the pineal gland, but is nearly undetectable in the retina; hydroxyindole O-methyltransferase mRNA levels exhibited a similar pattern. This supports the view that the source of circulating melatonin in primates is the pineal gland. The discovery in this study that rhesus pineal AANAT mRNA is high at all times is of special importance because it shows that posttranscriptional control of this enzyme plays a dominant role in regulating melatonin synthesis.


Physiology ◽  
2020 ◽  
Vol 35 (2) ◽  
pp. 86-95 ◽  
Author(s):  
Russel J. Reiter ◽  
Qiang Ma ◽  
Ramaswamy Sharma

In cancer cells, glucose is primarily metabolized to pyruvate and then to lactate in the cytosol. By allowing the conversion of pyruvate to acetyl-CoA in mitochondria, melatonin reprograms glucose metabolism in cancer cells to a normal cell phenotype. Acetyl-CoA in the mitochondria also serves as a necessary co-factor for the rate-limiting enzyme in melatonin synthesis, thus ensuring melatonin production in mitochondria of normal cells.


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