M. Sc. Razhan S. Othman
HOD medical lab
technique

 Define of melatonin.
 Biosynthesis and metabolism of melatonin.
 melatonin secretion and it levels and how it
work?
 Physiological role of melatonin .
 Adverse effect .

What is melatonin?
 Hormone that is naturally produced by the
pineal gland.
 Arone lerner in 1958 was discovered this
hormone.
 Pinal gland ,in humans resembling the shape
of a pine cone ,its location is either central in
the brain .
 The pineal weight in humans brain is 100-
150mg ,whereas in rat 1-1.5mg.

Biosynthesis:
 Generated from amino acid tryptophan and
serotonin
 Is made predominantly at night in the pineal
gland.
 Tryptophan hydroxylase activity where
presence in the mitochondrial
increase during darkness
about 2 fold.
melatonin

Metabolism :
 There are several metabolic pathways:
1-brain :one is the formation of N-acetyle-
5methoxykynurenamin after dioxygenase of melatonin
compound cleavage pyrol cycle.
2- liver : by dimethylation to N-acetyl serotonin.
**Metabolism pathway of exogenously administrated
melatonin in humans are reported half-lives 3 and 45
minute.

Melatonin secretion
 Melatonin secretion starts at 3-4 months of age
when nighttime sleeping consolidates.
 Peak levels at 1-3 years of age.
 Slightly lower levels through early adulthood.
 Marked decline in levels afterwards.
 Peak levels for 70 year olds is ¼ of levels for
young adults.

How melatonin works??
 Melatonin levels cycle
 Low levels during daylight, rise during
nighttime
 Peak levels between 11PM and 3AM
 Levels continue to cycle in constant darkness
 Can slowly adjust to environmental changes

Physiological role of melatonin
1-Radical scavenger
2-Sleep
3-Cancer
4-Immune system
5-Other

Radical scavenger
 Free radical =bearing one unpaired electron.
 Hydroxyl free radical (OH.), Is one of dangerous and reactive
radical.
 5% of all O2 taken in will be converted to superoxide anion O2.-
 Oxidative stress: continuous forming radical .e
 Oxidative stress can be increase by toxin,
excessive exercise, radiation, infection,
ischemia etc.
 Vitamin C and E also can act as radical
scavenger.

Sleep
 Melatonin is “opening the sleep gate “
 Suprachiasmatic Nucleus (SCN) is the site of
internal biological clock.
 Elevated melatonin level occur at night
coincident with sleep humans.
 Melatonin is not to be a direct soporific.

Cancer
 Melatonin is inhibitory action of tumor growth.
 The apparent melatonin induced suppression of
prolactin , when prolactin is a hormone that can
promote mammary cancer.
 Several studies reported that ,during the initial
state of tumor development ,melatonin is
increased an early stage of cancer with malignant
cells that do not growth.
 The relationship between pineal gland and cancer
is a dynamic.
 Doses of 10-20mg of melatonin to advanced
cancer patients in the afternoon.

Immune system
 Melatonin hormone directly effect of the
immune system when suppression of melatonin
production by propranolol or the inhibitor of
serotonin biosynthesis Para-
chlorophenylalanin resulted in reduced
immune responses toward T-dependent
antigens.

OTHER FUNCTION
 Melatonin can act as an antioxidant .
 Exogenous melatonin decrease leptin production .
 Reported that melatonin intake reduced blood
pressure during sleep ,without effect of the heart
rate.
 An important property of melatonin is its ability
to influence circadian rythmicity .
 One of the claimed action of melatonin that anti-
aging effect.
 Melatonin supplements by humans with jet lag,
delay sleep phase(alzheimers disease), epilepsy.

Adverse effects
 Excess melatonin can lead to daytime
sleepiness, impaired mental and physical
performance, hypothermia, and high levels of
prolactin
 Menstrual irregularities, impotence decreased
libido.