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.