The pineal gland, also referred to as the pineal body, the pineal region, or just "the pineal," was largely misunderstood until quite recently. It is a tiny, bulbous protrusion from the diencephalic roof in the brain (Reiter, 1987). It is located in the center of the brain, resting between the two cerebral hemispheres, and is the only "unpaired midline organ in the brain." For this reason, it was thought to be a "valve to regulate the flow of thought" In the Seventeenth Century, René Descartes wrote that the pineal gland "housed the seat of the rational soul." (Wurtman & Axelrod, 1965). In humans, the pineal gland weights approximately one hundred mg only one mg in rats. It is found in developing embryos, and while it is located close to the brain stem and communicates with the sympathetic nervous system, it does not have direct nerve connection to the brain. (Reiter, 1987) This means the pineal gland does not play a role in cognition or memory but is considered to be a part of the endocrine system as its primary function is the release of melatonin. Melatonin in turn has effects on the body's circadian rhythm, sex organs, immune system, and even infant deaths.
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The pineal gland works in conjunction with the eyes and the sympathetic nervous system to distribute melatonin to the rest of the body. Its cells are capable of functioning as photo receptors (Wurtman, Axelrod, & Kelly, 1968) and pineal activity is stimulated by dark and inhibited by light. Photic information is received through the retinas and converted to neural impulses to be sent via fibers to synapses in the suprachiasmatic nuclei or the hypothalamus. The impulses are then passed to the thoracic cord through an unknown pathway, out the spinal cord, and up to the superior cervical ganglion. These fibers then follow the same path as the blood vessels, form nerve bundles, and terminate in the pineal gland. The primary neurotransmitter associated with this system is norepenephrine which contains beta-adrenergic receptors. The number of receptors available depends on the period of the twenty-four hour light cycle, with more available at night (Reiter, 1987).
Once stimulated, the pineal gland begins the process of melatonin synthesis. Tryptophan is an amino acid received through food that collects in the pineal gland. Tryptophan is then broken down to produce serotonin, and then enzymes break serotonin down into melatonin. These chemicals function on a twenty-four hour cycle, with serotonin levels higher in the pituitary gland than in any other gland or organism in the body, especially during the light period. As a result of the increase of beta-adrenergic receptors, there are more frequent impulses received during the dark cycle and therefore more pineal activity and melatonin synthesis at night. Melatonin is then released into the blood stream, metabolized by the liver, and either secreted as urine or released back into the blood stream (Reiter, 1987).
There has been some discussion in the scientific community as to whether light or food were the dominant cues for the pineal gland and its regulation of the circadian clocks. Wu, Jin, Kato, and Fu examined both factors and their effect on the master clock found in the suprachiasmatic nucleus and on the peripheral clocks it was believed to control. They expected the master clock to be controlled by the light/dark cycle while the peripheral clocks were expected to respond more to food restriction. The results of their study supported their hypothesis in that photic regulation was determined to be the dominant cue in the synchronization of the pineal circadian system and had a strong control over the master clock. However, it was found that the pineal gland had less control over the peripheral clocks which did show strong response to a restricted-food diet (Wu, Jin, Kato, & Fu, 2008).
Research has shown that the pineal gland and melatonin are responsible for maintaining important biological clocks in animals and that damage to or removal of the pineal gland can have adverse consequences on the animal. Agez et al. conducted an experiment where they removed the pineal gland of rats, effectively halting melatonin reproduction. Half the rats received melatonin in their drinking water while the other half did not. The rats were placed in a dark room for twenty-four hours in order to simulate a twenty-four hour dark period. Researchers then killed one rodent per hour via decapitation and measured the melatonin levels in the rats and examined the state of the suprachiasmatic nuclei circadian rhythm. What they found was that the rats that ingested melatonin showed a continued circadian rhythm in the suprachiasmatic nuclei and maintained phase relationships with their partners. However, rats who were not administered melatonin did not maintain circadian rhythm. These results demonstrated not only that the pineal gland was important for the production of melatonin, but also that production was necessary to sustain circadian rhythm in the suprachiasmatic nuclei (Agez et al, 2009).
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Melatonin has been found to have some effect on the circadian rhythm in the development of sexual organs, though to what extent is still unclear. In rats, melatonin triggers the reproductive activity of rodents in the spring, and in its absence they fail to engage in sexual reproduction at the right time (Reiter, 1987). There have been several documented cases in humans where precocious sexual maturation occurred as a result of a pineal tumor. It was hypothesized that the pineal gland secretes a hormone responsible for regulating sexual maturation and without the hormone it can occur too soon (Wurtman, Axelrod, & Kelly, 1968). However, there were also some human cases found where pineal tumors were associated with delayed sexual maturation. In 1954 Julian I. Kitay, an endocrinologist at Harvard Medical School, reviewed the existing literature and concluded that the tumors associated with precocious sexual maturation did not originate in the pineal, but migrated there, and the decreased effects of the pineal gland were a result of that disease from the surrounding tissues. In contrast, tumors associated with delayed sexual maturation were generally found to be true pineal tumors and it was determined that pineal tumors and melatonin will suppress sexual maturation (Wurtman & Axelrod, 1965).
Maestroni, Conti, and Pierpaoli demonstrated that decrease or loss of circadian rhythm melatonin secretion could trigger a reduced response of antibodies to foreign pathogens, meaning a weakened immune system. However, returning the melatonin levels back to their normal level also returned the immune system back to normal. This suggests that the pineal gland plays a significant role in the maintenance of the immune system (Maestroni, Conti, & Pierpaoli, 1986).
Low levels of melatonin have also been linked to cases of Sudden Infant Death Syndrome (SIDS). Several studies, including Melatonin Concentrations in the Sudden Infant Death Syndrome by Sturner, Lynch, Deng, Gleason, and Wurtman (1990), conducted autopsies of infants who have died of SIDS and those who died as a result of complications other than SIDS. Samples of spinal fluid and blood were collected and the amount of melatonin found in each was compared. Results indicated that infants who died of SIDS had lower levels of melatonin than those who died of other causes in both their blood and spinal fluid. The lower levels in the spinal fluid indicated a pituitary issue and suggested some sort of abnormality there. It was also found the amount of melatonin in the spinal fluid directly correlated with the amount in the blood, indicating it may be possible to test blood levels in living infants to determine if they are at higher risk for SIDS and possibly prevent future instances of tragic deaths.
The pineal gland seems fairly simple in comparison to other brain regions in that its primary function is just the synthesis of melatonin and its secretion in the body. However, that one task alone serves a wide variety of important functions related to maintaining natural body rhythms, with effects ranging from sexual maturation and reproduction, to immune responses, to the sleeping and waking of infants. It comes as no surprise early philosophers two-thousand years ago believed it to be such a powerful, metaphysical structure.