MELATONIN: CHEMICAL STRUCTURE, FUNCTION AND USES - GEOGRAFÍA - 2025

The melatonin is a hormone present in humans, animals, plants, fungi, bacteria and even in some algae. Its scientific name is N-cetyl-5-methoxytryptamine and it is synthesized from an essential amino acid, tryptophan.

Melatonin is today considered a neurohormone that is produced by pinealocytes (a type of cell) of the pineal gland, a brain structure that is located in the diencephalon. Its most important function is the regulation of the daily sleep cycle, which is why it is used in some cases as a treatment for sleep disorders.

Melatonin molecule with chemical formula

The pineal gland generates melatonin under the influence of the suprachiasmatic nucleus, a region of the hypothalamus that receives information from the retina about daily patterns of light and dark.

Melatonin characteristics

One of the main characteristics of this molecule lies in its biosynthesis, which is highly dependent on changes in ambient lighting.

People experience a constant generation of melatonin in their brain, which decreases markedly by age 30. Likewise, from adolescence calcifications usually occur in the pineal gland, which are called corpora arenacea.

The synthesis of melatonin is partly determined by ambient lighting, thanks to its connection with the suprachiasmatic nucleus of the hypothalamus. That is, the higher the light, the lower the production of melatonin and the lower the light, the higher the production of this hormone.

This fact highlights the important role that melatonin plays in regulating people's sleep, as well as the importance of lighting in this process.

Melatonin has now been shown to have two main functions: regulating the biological clock and reducing oxidation. Likewise, melatonin deficits are usually accompanied by symptoms such as insomnia or depression, and could cause a gradual acceleration of aging.

Although melatonin is a substance synthesized by the body itself, it can also be observed in certain foods such as oats, cherries, corn, red wine, tomatoes, potatoes, walnuts or rice.

Likewise, melatonin is sold today in pharmacies and parapharmacies with different presentations and is used as an alternative to medicinal plants or prescription drugs to combat, mainly, insomnia.

Biosynthesis and metabolism

Melatonin is a substance that biosynthesizes from tryptophan, an essential amino acid that comes from food.

Chemical structure of tryptophan

Specifically, tryptophan is directly converted to melatonin through the enzyme tryptophanhydroxylase. Subsequently, this compound is decarboxylated and generates serotonin.

Darkness activates the neuronal system causing the production of a surge of the neurotransmitter norepinephrine. When norepinephrine binds to b1 adrenoceptors on pinealocytes, adenyl cyclase is activated.

Likewise, through this process, cyclic AMP is increased and a new synthesis of arylalkylamine N-acyltransferase (enzyme of melanin synthesis) is caused. Finally, through this enzyme, serotonin is transformed into melanin.

Regarding its metabolism, melatonin is a hormone that is metabolized in the mitochondria and cytchrome p in the hepatocyte, and is rapidly converted to 6-hydroxymelatonin. Later, it is conjugated with glucuronic acid and is excreted in the urine.

Melatonin, pineal gland and light

When the eyes receive sunlight, the production of melatonin in the pineal gland is inhibited and the hormones produced keep us awake. In turn, when the eyes do not receive light, melatonin is produced in the pineal gland and the human gets tired. Srruhh

The pineal gland is a structure found in the center of the cerebellum, behind the third cerebral ventricle. This structure contains pinealocytes, cells that generate indolamines (melatonin) and vasoactive peptides.

Thus, the production and secretion of the hormone melatonin is stimulated by fibers of the postganglionic nerve of the retina. These nerves travel through the retinohypothalamic tract to the suprachiasmatic nucleus (hypothalamus).

When found in the suprachiasmatic nucleus, the postganglionic nerve fibers traverse the superior cervical ganglion to reach the pineal gland.

Once they reach the pineal gland, they stimulate the synthesis of melatonin, which is why darkness activates the production of melatonin while light inhibits the secretion of this hormone.

Although external light influences the production of melatonin, this factor does not determine the overall function of the hormone. That is, the circadian rhythm of melatonin secretion is controlled by an endogenous pacemaker located in the suprachiasmatic nucleus itself, which is independent of external factors.

However, ambient light has the ability to increase or slow down the process in a dose-dependent manner. Melatonin enters the bloodstream by diffusion, where it peaks between two and four in the morning.

Subsequently, the amount of melatonin in the bloodstream gradually decreases during the remainder of the dark period.

Physiological variations

On the other hand, melatonin also presents physiological variations depending on the age of the person. Up to three months of life, the human brain secretes low amounts of melatonin.

Subsequently, the synthesis of the hormone increases, reaching concentrations of about 325 pg / mL during childhood. In young adults the normal concentration ranges between 10 and 60 pg / mL and during aging the production of melatonin decreases gradually.

Factors that modulate melatonin secretion

The entry of light into the SCN prevents the pineal gland from producing melatonin and, conversely, the production and secretion of melatonin increases during the period of darkness. Zhiqiang Ma, Yang Yang, Chongxi Fan, Jing Han, Dongjin Wang, Shouyin Di, Wei Hu, Dong Liu, Xiaofei Li, Russel J. Reiter, and Xiaolong Yan

Currently, the elements that are capable of modifying melatonin secretion can be grouped into two different categories: environmental factors and endogenous factors.

Environmental factors

Environmental factors are mainly formed by the photoperiod (seasons of the solar cycle), the seasons of the year and the ambient temperature.

Endogenous factors

Regarding endogenous factors, both stress and age appear to be elements that can motivate a reduction in melatonin production.

Release patterns

Likewise, three different patterns of melatonin secretion have been established: type one, type two and type three.

The type one pattern of melatonin secretion is seen in hamsters and is characterized by a sharp spike in secretion.

The type two pattern is typical of the albino rat, as well as humans. In this case, the secretion is characterized by a gradual increase until reaching the maximum secretion peak.

Finally, the type three stop has been observed in sheep, it is also characterized by presenting a gradual increase but differs from type two by reaching a maximum level of secretion and staying for a time until it begins to decrease.

Pharmacokinetics

Melatonin is a widely bioavailable hormone. The body does not present morphological barriers for this molecule, so melatonin can be absorbed rapidly through the nasal, oral or gastrointestinal mucosa.

Likewise, melatonin is a hormone that is distributed intracellularly in all organelles. Once administered, the peak plasma level is reached 20-30 minutes later. This concentration is maintained for about an hour and a half and then declines rapidly with a half-life of 40 minutes.

At the brain level, melatonin is produced in the pineal gland and acts as an endocrine hormone, since it is released into the bloodstream. The brain regions of action of melatonin are the hippocampus, the pituitary, the hypothalamus and the pineal gland.

Pineal gland. Nephron

On the other hand, melatonin is also produced in the retina and in the gastrointestinal tract, places where it acts as a paracrine hormone. Likewise, melatonin is distributed by non-neural regions such as the gonads, the intestine, blood vessels, and immune cells.

Features

The main function of this hormone lies in the regulation of the biological clock.

Memory and learning

Melatonin receptors appear to be important in the learning and memory mechanisms of mice; this hormone could alter electrophysiological processes associated with memory, such as long-term enhancement.

Immune system

On the other hand, melatonin influences the immune system and is related to conditions such as AIDS, cancer, aging, cardiovascular diseases, daily rhythm changes, sleep and certain psychiatric disorders.

Development of pathologies

Certain clinical studies indicate that melatonin could also play an important role in the development of pathologies such as migraines and headaches, since this hormone is a good therapeutic option to combat them.

On the other hand, melatonin has been shown to reduce tissue damage caused by ischemia, both in the brain and in the heart.

Medical use

The multiple effects that melatonin causes on the physical and cerebral functioning of people, as well as the ability to extract this substance from certain foods has motivated a high degree of research on its medical use.

However, melatonin has only been approved as a drug for the short-term treatment of primary insomnia in people over 55 years of age. In this sense, a recent study showed that melatonin significantly increased total sleep time in people who suffered from sleep deprivation.

Research on melatonin

Although the only approved medical use for melatonin is in the short-term treatment of primary insomnia, multiple investigations are currently underway on the therapeutic effects of this substance.

Specifically, the role of melatonin as a therapeutic tool for neurodegenerative diseases such as Alzheimer's disease, Huntington's chorea, Parkinson's disease or amyotrophic lateral sclerosis is being investigated.

This hormone could constitute a drug that in the future will be effective to combat these pathologies, however, today there are hardly any works that provide scientific evidence on its therapeutic usefulness.

On the other hand, several authors investigate melatonin as a good substance to combat delusions in elderly patients. In some cases, this therapeutic utility has already been shown to be effective.

Finally, melatonin presents other research avenues that are somewhat less studied but with good future prospects. One of the most popular cases today is the role of this hormone as a stimulating substance. Research has shown that giving melatonin to subjects with ADHD reduces the time it takes to fall asleep.

Other therapeutic areas of research are headache, mood disorders (where it has been shown to be effective for the treatment of seasonal affective disorder), cancer, bile, obesity, radiation protection and tinnitus.

References

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