Search A Light In The Darkness

Monday 14 May 2007

Melatonin

In higher animals melatonin is produced by pinealocytes in the pineal gland (located in the brain) and also by the retina, lens and GI tract. It is naturally synthesized from the amino acid tryptophan (via synthesis of serotonin) by the enzyme 5-hydroxyindole-O-methyltransferase.

Production of melatonin by the pineal gland is under the influence of the suprachiasmatic nucleus of the hypothalamus (SCN) which receives information from the retina about the daily pattern of light and darkness.

Melatonin produced in the pineal gland acts as an endocrine hormone since it is released into the blood.

By contrast, melatonin produced by the retina and the gastrointestinal (GI) tract acts as a paracrine hormone.

The Melatonin signal forms part of the system that regulates the circadian cycle, but it is the CNS that controls the daily cycle in most components of the paracrine and endocrine systems rather than the melatonin signal (as was once postulated).

Normally, the production of melatonin by the pineal gland is inhibited by light and permitted by darkness. For this reason melatonin has been called "the hormone of darkness". The secretion of melatonin peaks in the middle of the night, and gradually falls during the second half of the night. Until recent history, humans in temperate climates were exposed to up to eighteen hours of darkness in the winter. In this modern world, artificial lighting typically reduces this to eight hours or less per day all year round. Even low light levels inhibit melatonin production to some extent, but over-illumination can create significant reduction in melatonin production. Reduced melatonin production has been proposed as a likely factor in the significantly higher cancer rates in night workers, and the effect of modern lighting practice on endogenous melatonin has been proposed as a contributory factor to the larger overall incidence of some cancers in the developed world.

As inadequate as blood concentrations may be in brightly-lit environments, some scientists now believe that people's overnight output of melatonin can be further jeopardized each time they interrupt their sleep and turn on a bright light (suggesting that the lower brightness level of a nightlight would be safer). Others suggest that such short exposures do no harm.

As an antioxidant
Although the primary site of melatonin's action is via the melatonin receptors, melatonin evolved first as an antioxidant, and has only this primitive and primary function in many lower life forms.

Melatonin is a powerful antioxidant that can easily cross cell membranes and the blood-brain barrier. Unlike other antioxidants, melatonin does not undergo redox cycling, the ability of a molecule to undergo reduction and oxidation repeatedly. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants, counterintuitively promoting free radical formation. Melatonin, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.

The antioxidant activity of melatonin may reduce damage caused by some types of Parkinson's disease, may play a role in preventing cardiac arrhythmia and may increase longevity; it has been shown to increase the average life span of mice by 20% in some studies.

In immune system
The body of research is overwhelmingly supportive of the claim that melatonin interacts with the immune system. Melatonin may help fight disease, but its true role in disease treatment is unknown. There have been very few trials designed to judge the effectiveness of melatonin in disease treatment. Most existing data are based on very small, incomplete, clinical trials.

Melatonin is an immunoregulator that enhances T cell production somewhat. When taken in conjunction with calcium, it is a very potent immunostimulator of the T cell response. Due to these immunoregulatory effects, it is used as an adjuvant in many clinical protocols; conversely, the increased immune system activity may aggravate autoimmune disorders.

In dreaming
Many melatonin users have reported an increase in the vividness or frequency of dreams. High doses of melatonin (50mg) dramatically increased REM sleep time and dream activity in both narcoleptics and normal people.

It is interesting to note that many psychoactive drugs, such as LSD and cocaine, increase melatonin synthesis. It has been suggested that nonpolar (lipid-soluble) indolic hallucinogenic drugs emulate melatonin activity in the awakened state and that both act on the same areas of the brain.


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