Melatonin was first identified in 1958 by a Yale dermatologist (Pearce, 2007). This powerful
hormone is secreted by the pineal gland and has been linked to a wide variety of functions in the body. Two
functions that have been directly linked to melatonin by extensive research has been its involvement in
seasonal responses and circadian rhythms (Ekmekcioglu, 2006). Although these are the most researched
categories of functions involving melatonin, this hormone has been tied to an extensive amount of other
functions. Melatonin has been found to regulate reproduction cycle in mammals, lower core body
temperature, act as a natural antioxidant, bind to calmodulin, and has also been linked to a number of
successful treatments of seizures and Alzheimer’s disease (Turek, 2004). Rohr and Ekmekcioglu have
extensively described all the research done on melatonin in the body and the effects of a decrease (2002,
2006).
There are two types of melatonin receptors; ML1 and ML2 (Turek, 2004). Along with serotonin
and beta-adrenergic receptors, ML1 is part of a large family of receptors. This receptor is very important to
the nervous system. The two subsets of ML1 are MT1 and MT2, both showing very important roles in the
hypothalamus. Screenings have shown that these receptors have shown up an various tissues and have been
detected in many organs. Some places that these receptors are found are in the retina, cardiovascular
system, liver, gallbladder, immune cells, prostate and breast epithelial cells, and adipocytes. This hormone
is most abundant at night, because it is triggered by environmental darkness and many environmental cues.
Melatonin is also most abundant during winter opposed to summer because the light change during these
times. Many people have confused this hormone as an inducer of sleep but in fact, it actually acts as a
signal giver to the body indicating time of darkness (Turek, 2004). These signals and the release of
melatonin is controlled by a part of the hypothalamus called the Suprachiasmatic Nucleus. Circadian
rhythms are masterly controlled by the Suprachiasmatic nucleus, commonly known as the SCN. The SCN
has expressed an abundant amount of receptors for melatonin which scientifically shows that these two
communicate often. The SCN controls the release of melatonin through a multi-synaptic pathway. The
retinal superior cervical ganglion create a release of norepinephrine onto pinealocytes when it gets dark out.
These pinealoctyes create an increase in melatonin synthesis. The increase in melatonin then, in turn,
provides the SCN with reinforcement and stabilization of circadian rhythms (Ekmekcioglu, 2006).
Although it is has been miscued as an inducer of sleep, it still does prepare our body for bedtime, says
Ekmekcioglu. Melatonin, when released, vasodilates the distal body regions which decreases core body
temperature and with this decrease, we become more drowsy. Not only does this busy hormone regulate
circadian rhythms but it is also very well known to adjust reproduction cycles in mammals and the onset of
puberty in humans.
Melatonin ML1 receptors have shown up in almost all parts of the body and have expressed a
great significance in most of them. With the SCN being the most important, the retina comes in second.
The retina is the reason for the release of melatonin because that is how the light-dark senses are
established, unless one is blind (Turek, 2004). Another part of the brain that ML1 receptors are found is the
hippocampus, especially in pyramidal neurons. The MT1 receptor is expressed more for the main output of
the hippocampus, the CA 1 subfield. The MT2 receptor is expressed more for the glutamatergic excitatory
inputs. Once this was found, many scientists had proof to start giving Alzheimer's patients exogenous
melatonin that are specific for these receptors which was proven to actually help many of them. MT1
receptors were solely found in the central dopaminergic system which is important for psychological
factors. This discovery has lead to many rehabilitation centers administering melatonin as a reinforcing
action drug since it triggers reward. Another powerful place that this hormone’s receptors have been found
is in cardiovascular systems. Although this part of the body has not yet been completely researched, it has
been found that melatonin can vasoconstrict arteries to promote sleepiness. It is unclear to why these
receptors are found in the heart but research should be coming across that soon. The gallbladder is one of
the most mysterious organs of the body that the receptors were found in. The levels of receptors exceed
those of plasma! This has been reasoned to be because it modulates ion transport motility and it may
interfere with nitric oxide signaling which could influence contraction. After many experiments were
conducted, it was found that melatonin influences the release of HCO-3 from the duodenal mucosa to
balance out the hydrochloric acid from the stomach but this release was found to be under nervous control.
Lastly, besides being abundant in the immune system, it has been found that melatonin is a major
contributor to cell proliferation in cutaneous melanoma cells in the skin. Also, this hormone created almost
a shield for fibroblasts and keratinocytes from UVB damage.
If a person is exposed to light during the normal time of darkness, this person will have suppressed
melatonin secretion. Recently, there has been an abnormal amount of breast, testicular, and liver cancers in
industrialized countries. There has been research done on this link to melatonin. One hypothesis is that
because of the high exposure to light at night time, melatonin is unable to be produced which then does not
allow it to be circulated around the body as a powerful antioxidant to the places that have the melatonin
receptors. Melatonin levels are found to be important in breast tissue not only because of it’s antioxidant
effects but also because it inhibits proliferation in estrogen-receptor alpha and it also facilitates the binding
of estrogen by inhibitory effects on calmodulin.
Melatonin, about two hours before bedtime, will increase, peaking in the middle of the night, and
then falls gradually after the peak (Rohr, 2002). In blind individuals, it has been shown that melatonin is
actually in a “free flowing” cycle (Ekmekcioglu, 2006). Many causes have been linked to a delay in
melatonin production. A lot of this delay has to do with our busy lifestyles. Jetlag, sleeping disorders, and
night work shifts are all culprits to why melatonin is not where it should be in a great portion of our society.
It has also been linked that financial, marital, and social problems may cause melatonin phase delay (Rohr,
2002) Delayed sleep phase syndrome (DSPS) is a very well known sleep disorder where sleep is not able to
come until usually about four a.m. In this sleeping disorder, melatonin rhythm is delayed by pushing it back
at least seven hours. The peak is at about six a.m. and the high levels persist during early morning. The
opposite of DSPS is ASPS also known as Advance sleep phase syndrome. This is when a person falls
asleep around eight a.m. and will not wake up until three a.m. the next day. These melatonin levels have
not been experimentally tested to draw scientific conclusions on. When a person is associated with
desynchronized circadian rhythms, they are more likely to weight gain, oversleeping, and have
carbohydrate cravings (Ekmekcioglu, 2006).
Melatonin has been experimentally linked to reproduction cycles and was thought to bring upon
Seasonal affective disorder (SAD). Although humans are non-seasonal breeders, it has been found that
birth rates are correlated to environmental light which is linked to the production of melatonin, says Rohr
(2002). This might seem like a far reach, saying that melatonin has an impact on our reproduction cycle just
because of the light but it is shown in many other species of animals that melatonin mediates the
reproduction cycle. This is also believed to pass to humans also. High melatonin has been shown to
decrease reproduction in humans which is why there are more conceptions reported for the summer since
melatonin levels are decreased. The hypothalmaic GnRH pulse generator, which is a part of the body that
decreases sexual hormones, is inactivated during the change of season from summer to winter because
melatonin levels change. Along with our reproduction clock, many researchers believed that melatonin had
an effect on SAD but this has found to be untrue, says Rohr (2002). Many thought that because melatonin
was sensitive to light that the increase of it during winter caused a depression. This was proven wrong
when it was found that serotonin levels actually decreased during the winter. When a person was exposed
to light to help their depression, their melatonin rhythms stayed the same as before the light was introduced.
It was also found that people with darker eye color might be more susceptible to SAD because less light
intensity is allowed to pass through their eyes.
Because of how new this hormone is, there is a very well known and established hypothesis called
“The Melatonin Hypothesis“ (Rohr, 2002). This hypothesis states “excess exposure to environmental light
contributes to breast cancer risk via impaired pineal secretion of melatonin” (Ekmekcioglu, pg 8). This
hypothesis also goes into state that blind people should exhibit lower levels of breast cancer since their
melatonin levels are higher than people who are not blind. The melatonin hypothesis also gives many
reasons to why a dietary supplement of melatonin should not be given as an over the counter drug yet. If
used incorrectly, it can be a hypnotic and can promote sedation in humans when administered during the
day when melatonin levels are expected to be low (Turek, 2004). Instead, a melatonin receptor agonist
would be more effective than exogenous melatonin since it does not show as drastic affects.
Melatonin is an abundant hormone that has to continue to be researched and understood. It has
been found in many parts of our body and where one does understand it, one does see how important it is
for our body to have. This is a type of hormone that is sensitive to light and can be easily lost if one does
not take care of oneself. Abnormal production of melatonin has been linked to sleeping difficulties. It plays
a significant role in regulating circadian rhythms and seasonal responses but has been found to maintain our
body functions in other ways than simply that. Unlike many other hormones, melatonin is not suggested to
be taken as a dietary supplement because of its sometimes unwanted effects (Ekmekcioglu, 2006)