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Pineal gland and Melatonin
Lecture NO:2nd MBBS
Dr Muhammad Ramzan
Pineal gland – Location and role
• Pineal gland is a small organ, shaped like a Pine cone.
• is located at the midline of the brain at the roof of 3rd ventricle
• Pineal body is present in human as well as in animals
• It secretes a hormone – the Melatonin that informs the body
parts about environmental light
Pineal gland – its location
Melatonin (Mell.) – the definition
3rd eye
• A protein hormone produced by the Pineal gland in the brain
• Communicates information about environmental light to :
• The different parts of the body through Retina – 3rd eye
• Is best known for helping to regulate the body's circadian
sleep-wake cycle in human
Melatonin – the background
the light of night
• Mell is the naturally occurring protein found in animals
including mammals; plants Insects and microbes
• Is a derivative of essential AA Tryptophan
• Its production is influenced through the detection of light
and darkness by the Retina of the eye
• Mell synthesis is inhibited by light and stimulated in the
absence of light – the hormone of darkness
• ↑ Melatonin is present in Tomatoes; Bananas, Spinach and almonds
Foods high in Mell
Melatonin – the Photoperiod
length of the day vs. night
• It is the daily exposure of an animal to light and has
important effects on its :
• Growth, development and breading/reproductive season
• Can be described as length of the Day Versus Night and
• is different in Winter and Summer
Melatonin secretion and age
no secretion at < 3 months
• Very little melatonin is secreted by the children < 3 months
• Its secretion ↑es, becomes circadian as the infant grows
and is highest at the age of 1- 3 years
• Mell production starts falling after puberty and virtually
disappears in the elderly
• A phenomenon which could help to explain why sleep
disturbances are more prevalent among old age
Mell – Target tissues with GPRC
Hypothalamic nuclei, GIT and retina
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Target tissues are the ones that express Mell receptors
Mel.1 and Mel.11 (Mell A or Mell B) - GPCR
Major target tissues for the Mell are :
CNS – Supra Chiasmic and PVN nuclei and ant. Pituitary
Retina; GIT; Ovary and blood vessels
Total Mell GIT secretion is 400 times than from Pineal gland
Melatonin synthesis – from Tryptophan
Hydroxylation and Methylation
• Tryptophan, an amino acid is taken up by the Cells of the
Pineal gland from the circulation
• Undergoes Hydroxylation to 5 - Hydroxy Tryptophan
• 5- Hydroxy Tryptophan is Decarboxilated to the Serotonin
• Serotonin is Methylated to the Melatonin ( an Indole)
• Melatonin is rapidly metabolized in liver by Hydroxylation
and Conjugation and then excreted in urine
Melatonin – the biosynthesis
Summary for the pathway of Mell synthesis
• Photo receptor cells of the retina perceives the light status
• Produce and send signals to the hypothalamic nucleic which include:
• Suprachiasmatic,PVN and then to the Superior Cervical ganglion via
spinal inter mediolateral cell column that sends :
• Sympathetic nerve fibers to the cells of Pineal gland to ↑ Mell
synthesis at night
• Mell production induces sleep by ↓ body temp. and respiratory rate
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Melopsin is a photosensitive retinal pigment – a member of retinal proteins Opsin
Melatonin synthesis – the pathway
Melopsin is a photosensive
Mell synthesis – signal pathway
eye to Pineal gland
Mell synthesis and mechanism of action
Release of NE (nor epinephrine)
Regulation of Mell by Nor epinephrine
nor epinephrine(NE) is released at night
• Photoreceptor retinal cells are activated in the night and
sends signals across the pathway for Mell. synthesis
• Mell production is regulated by the nor epinephrine, which
is released from the Sympathetic nerve fibers
• These fibers are conveyed to the Pineal gland by the
Superior Cervical ganglion
• Activation of these fibers releases the nor epinephrine
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SCN regulates Mell synthesis during the day
SCN prevents release of NE
• Nor epinephrine binds to the β – adrenergic receptors on
the Pineal cells and activates Adenylate Cyclase :
• that converts ATP to cAMP (2nd messenger) that stimulates
the Mell synthesis from Tryptophan
• During the day, SCN inhibits the release of Nor epinephrine
and Mell synthesis
• SCN nucleus regulates Circadian oscillation in brain
Melatonin – The mechanism of action
GPCR and 2nd messenger
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Melatonin is a protein hormone and acts as such
Melatonin acts through Receptors in mammals :
Mell A and Mell B (Mel.1 and Mel 2) - GPCR
GPCR are expressed on the cells membranes of the:
Target tissues : Retina; GIT, ovary, blood vessels,SCN,
PVN and ant. Pituitary gland
Melatonin – The mechanism of action cont.
• Mell binds to the extracellular domain of the GPCR
• Produces conformation changes in the G- protein
• Exchanges GDP for α GTP and activates membranous
enzyme Adenylate Cyclase which converts :
• ATP to CAMP – the 2nd messenger
• cAMP, Phosphorylates various intracellular proteins and
enzymes to carry out Melatonin action
Mell – the mechanism of action
Biological effects of Melatonin
• Mell maintains the body Circadian Sleep- wake cycle and promotes the
sleep via SCN
1
• Regulates the secretion of hypothalamic and ant. Pituitary hormones
like GH, FSH and LH
2
• Manipulates the breeding season in animals like sheep
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• Regulates the distribution of Melanin pigments in lower species like
amphibians, tadpole/frog and birds
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Circadian Rhythm
Mell – Biological effects
Mell – Biological effects
• It is an antioxidant and Improves the function of the
lymphoid tissues of the immune system
• Provides protection against the malignancies- GIT; ovary
Liver, Pancreas and breast
Mell uses - Sleep Disorders and
alteration in breeding season
• Melatonin is used in certain sleep disorders when there
is disturbance in sleep- wake cycle
• This happens in Shift workers, International business
travelers and Jet lag
• Used for sleep disturbances in old age
• Melatonin is used to manipulate breeding season to
have 2/year instead of one especially in sheep
Melatonin for sleep disorders.Remeltion(FDA approved)
Tablets 3/5mg. capsules, liquid and skin spray
Biological effects of Mell