1. Pineal gland and Melatonin Lecture NO:2nd MBBS
Dr Muhammad Ramzan

2. 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

3. Pineal gland – its location

4. 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

5. 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

6. Foods high in Mell

7. 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

8. 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

9. Mell – Target tissues with GPRC Hypothalamic nuclei, GIT and retina
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

10. 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

11. Melatonin – the biosynthesis

12. 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
Melopsin is a photosensitive retinal pigment – a member of retinal proteins Opsin

13. Melatonin synthesis – the pathway Melopsin is a photosensive

14. Mell synthesis – signal pathway eye to Pineal gland

15. Mell synthesis and mechanism of action Release of NE (nor epinephrine)

16. 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

17. 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

18. Melatonin – The mechanism of action GPCR and 2nd messenger
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

19. 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

20. Mell – the mechanism of action

21. Biological effects of Melatonin
Mell maintains the body Circadian Sleep- wake cycle and promotes the sleep via SCN
Regulates the secretion of hypothalamic and ant. Pituitary hormones like GH, FSH and LH
Manipulates the breeding season in animals like sheep
Regulates the distribution of Melanin pigments in lower species like amphibians, tadpole/frog and birds

22. Circadian Rhythm

23. Mell – Biological effects

24. 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

25. 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

26. Melatonin for sleep disorders. Remeltion(FDA approved) Tablets 3/5mg
Melatonin for sleep disorders.Remeltion(FDA approved) Tablets 3/5mg. capsules, liquid and skin spray

27. Biological effects of Mell