Melatonin & the Pineal Gland The focus of this work is to examine melatonin and the pineal gland. Towards this end, this study examines the literature in this area of study and reports on the findings. The work of Turgut and Kumar (1996) addresses information on the pineal gland, "epiphysis…a small gland in the brain. Stated as that the chief product of pineal gland is that of melatonin. Aleandri, Spina and Morini report that the pineal gland hormonal activity "is influenced by both the dark-light cycle and the seasonal cycle, causing it to play an important role in the neuroendocrine control of reproductive physiology."

Melatonin & The Pineal Gland

The work of Turgut and Kumar (1996) addresses information on the pineal gland, "epiphysis…a small gland in the brain. Stated as that the chief product of pineal gland is that of melatonin. Aleandri, Spina and Morini report that the pineal gland hormonal activity "is influenced by both the dark-light cycle and the seasonal cycle, causing it to play an important role in the neuroendocrine control of reproductive physiology." This is reported to be "especially evidence in seasonal breeding animals, in which reproductive function is clearly influenced by seasonal variations in the duration of night and day." (1996, p.225) Aleandri, Spina and Morini additionally stated that the pineal gland's important was realized in the 16th century when it was believed to be the "seat of the soul." (1996, p.225)

I. Pineal Gland as Regulator

Reported is that the pineal gland "Through its endocrine activity, via mechanisms and physiological correlations that are not yet entirely understood, the pineal regulates or takes part in the control of numerous functions of an organism." (Aleandri, Spina and Morini, 1996, p.225) According to the work of Borjigin and Snyder (1999) the pineal gland

"expresses a group of proteins essential for rhythmic melatonin production. This pineal-specific phenotype is the consequence of a temporally and specially controlled program of gene expression. Understanding of pineal circadian biology has been greatly facilitated in recent years by a number of molecular studies, including the cloning of N-acetyltransferase, the determination of the in vivo involvement of the cAMP-inducible early repressor in the regulation of N-acetyltransferase, and the identification of a pineal transcriptional regulatory element and its interaction with the cone-rod homeobox protein. Likewise, appreciation the physiological roles of melatonin has increased dramatically with the cloning and targeted knockout of melatonin receptors. With these molecular tools in hand, we can now address more specific questions about how and why melatonin is made in the pineal at night and about how it influences the rest of the body." (Borijgin and Snyder, 1999, p.1)

II. Functions of the Pineal Gland

Arendt (2003) writes that the pineal gland from all appearances serves the same function in all mammals studied to date. The report states that the pattern of secretion of the major hormone, melatonin, "conveys information concerning light-dark cycles to the body physiology for the organization of seasonal and circadian rhythms." (p.1) Arendt states additionally "The pineal gland is part of the visual system and mammalian pinealocytes are derived evolutionarily from the pineal photoreceptors of lower vertebrates. The in-uence of the pineal gland on the circadian system appears to be more important in lower vertebrates than in mammals. In some reptiles and birds, the pineal appears to act as a central circadian rhythm generator. " (2003) Reported as well is the following information:

"In house sparrows (Passer domesticus), pinealectomy leads to arrhythmicity which can be restored by transplanting a pineal from another bird (Menaker et al., 1981). The circadian phase of the donor bird is conveyed to the host with the transplant. It is possible to culture pineal explants and dispersed pineal cells from ?sh, lizards and birds, and these preparations retain their circadian melatonin production in vitro. In contrast, the mammalian pineal does not retain endogenous rhythmicity in culture. The retina of lower vertebrates also generate melatonin rhythms in culture and the hamster retina (maintained at low temperature; Tosini and Menaker, 1996) can show the same phenomenon, which suggests that there may be a circadian pacemaker in the mammalian eye." (p.13) Arnedt reports that melatonin is synthesized within the pineal gland itself, in the retina and possibly in some other sites" but it is stated that in mammals, the majority and in some cases all of the hormone reaching peripheral sites is "derived from the pineal and pinealectomy leads to a great reduction and in the majority of cases in concentrations that cannot be detected in melatonin circulation. Arnedt reports that melatonin is synthesized from "tryptophan via 5- hydroxylation by tryptophan-5-hydroxylase to 5-hydroxytryptophan,...

The study findings note that the pineal gland is "the primary target of fluoride accumulation within the body." (2012) The pineal gland is comprised of soft tissue in an adult and is stated to contain "more fluoride than any other soft tissue in the body and in fact a level stated at "~300 ppm [is] capable of inhibiting enzymes. Also comprising part of the pineal gland is hard tissue" which is reported as accumulating "more fluoride (up to 21,000 ppm) than any other hard tissue in the body (e.g. teeth and bone)." (Fluoride Action Network, 2012, p.1)
It is reported that an experiment was conducted for the purpose of determining if accumulated fluoride might affect the functioning of the pineal gland and specifically if the gland's regulation of melatonin would be affected. Conclusions of the study report "… the human pineal gland contains the highest concentration of fluoride in the body. Fluoride is associated with depressed pineal melatonin synthesis by prepubertal gerbils and an accelerated onset of sexual maturation in the female gerbil. The results strengthen the hypothesis that the pineal has a role in the timing of the onset of puberty. Whether or not fluoride interferes with pineal function in humans requires further investigation." (Fluoride Research Network, 2012, p.1)

Bowen (2003) writes that the pineal gland serves to communicate information about the environmental lighting to parts of the body and that melatonin has the capacity to "entrain biological rhythms and has important effects on reproductive function of many animals. The light-transducing ability of the pineal gland has led some to call the pineal the 'third eye'." (p.1) Bowen states that serotonin is a neurotransmitter that is "derived from the amino acid typotophan and is a precursor of melatonin. Serotonin is stated to be acetylated in the pineal gland and to then be "methlyated to yield melatonin. This is illustrated as follows which has been adapted from the work of Bowen.

Figure 1

It is noted that the eyes receiving light exposure serves to dramatically impact synthesis and secretion of melatonin and it is stated that the "fundamental patterns observed is that serum concentrations of melatonin are low during the daylight hours and increase to a peak during the dark." (Bowen, p.1)

Stated as examples of the circadian rhythm in melatonin secretion in humans is that illustrated in the following figure in which dark gray is representative of night and serum melatonin levels displayed for two individuals (light blue vs. yellow). The blood levels of melatonin are not detectable during daylight hours however, these levels experience a sharp rise in nighttime hours. The melatonin secretion duration daily is reported as "directly proportional to the length of the night." (Bowen, 2003, p.1)

Figure 2

Examples of the Circadian Rhythm in Melatonin Secretion in Humans

Source: Bowen (2003)

The work of Buscemi, et al. (2004) reports a study by the Agency for Healthcare Research and Quality (AHRQ) stated to be developing scientific information and other organizations on which they can base clinical guidelines, performance measures and other quality improvement tools." (p.1) It is reported that it is indicated in studies that sleep disorders impact approximately 50 to 70 million Americans or 20% of the population. A sleep disorder exists when the individual has a "lower quality of sleep [resulting] in impaired functioning or excessive sleepiness. Insomnia, literally "inability to sleep," has various etiologies and is the most common sleep disorder, affecting between 6 to 12% of the adult population. In addition to the adult population, difficulties initiating and maintaining sleep are very common in children, affecting about 15 to 25% of this population." (Buscemi, et al., 2004)

Buscemi et al. reports a study that reviewed the utilization of melatonin for sleep disorder treatment. Biomedical databases were included in the information researched with literature searches reported as being "limited to English-lanugae reports of studies on human subjects with no age, gender or ethnicity restrictions. Reports of Clinical 1, Clinical 2, or Clinical 3 randomized clinical trials, quasi-randomized controlled trials, prospective…