04 Melatonin

What is the biochemical classification of melatonin

Amine

What cells makes up the pineal gland

Pinealocytes and glial cells

What hormone do pinealocytes in the pineal gland secrete

Melatonin

What is the function of glial cells

Support and protect the neurons of the central (and peripheral) nervous system

What is the function of pineal glands in MAMMALS

Synchronizes circadian rhythm, controls retinal function, controls reproductive cycles in seasonally breeding animals, participation in control of thermoregulation and sleep

What other unique function does pineal glands have in SOME mammals

regulates reproductive hormones, but this only applies to animals that are short or long day breeders: has effect on neurons that stimulate GnRH

What happens to pineal gland as we age

calcifies

How is melatonin release controlled by light-dark cycle

Melatonin is secreted only during darkness, serum levels of melatonin rise to peak in midst of dark cycle, peak melatonin levels are seen during childhood and decrease progressively during adulthood and aging

How does pineal gland communication change based on seasonal information/length of days

Short days = more melatonin is produced, long days = less melatonin is produced

How is melatonin synthesized?

Tryptophan is hydroxylated to form 5-hydroxytryptophan after being taken up by pinealocytes, 5-hydroxytryptophan is turned into serotonin, which can be turned into N-acetylserotonin, which turns into melatonin

Explain process of melatonin synthesis

Tryptophan is taken up by pinealocytes from the blood to convert into melatonin, light inhibits melatonin synthesis

How is melatonin secretion increased in darkness?

Activity of rate limiting enzyme in melatonin synthesis pathway (N-acetyl transferase) increases during darkness, then increasing melatonin production and release

How is melatonin metabolized?

Metabolized in liver by cytochrome P450 enzyme CYP1A2 to 6-hydroxymelatonin

What is done to metabolites before excretion during the catabolic process?

Conjugated with sulfuric acid or glucuronic acid for excretion in urine

Which two hormones regulate skin color in amphibians and how?

MSH and melatonin, regulate dispersal or aggregation of melanophores and iridophores

What are melanophores

Cells that produce melanin

What are melanosomes

Melanin-filled pigment granules in the skin

What are iridophores

pigment cells that reflect light in the skin; dispersal lightens skin, aggregation darkens the skin

Do iridophores synthesize pigment?

No, they reflect light in amphibian skin

What stimulates iridophore dispersal

stimulated by melatonin (which only causes dispersal)

What stimulates iridophore aggregation

stimulated by MSH (which only causes aggregation)

Desribe neural pathway between retina and pineal gland

SLIDE 8 PAGE 4

Describe the anatomy of the retina and retinal pathway

Retina is at the back of the eye, light first enters through ganglion cells, to amacrine cell, bipolar cells, horizontal cells, photoreceptor cells (rods and cones), then choroid

How do photoreceptor cells process light

Upon activation, light energy is converted to electrical impulse that tracks to optic nerve

GO TO PAGE 5, SLIDE 10

and describe the anatomy

What is the journey of electrical stimulus from light

Decrease in light leads to melanopsin containing ipRGC cells, suprachiasmatic nucleus in hypothalamus, to the paraventricular nucleus in hypothalamus, to the spinal neurons, to the superior cervical ganglion which results in decrease in norepinephrine, increasing activity of serotonin N-acetyl transferase in pineal gland, leading to production of N-acetyl serotonin, then an increase in melatonin (page 6 slide 12)

DESCRIBE PATHWAY of MELATONIN on SLIDE 13 PAGE 7

slide 13 page 7

WHat type of receptor are MT receptors (MT1 and MT2)?

G-coupled protein receptors

Do MT1/2 receptors activate excitatory or inhibitory pathways?

Both

TASK: DRAW A MT1 or MT2 RECEPTOR AND THE PATHWAY IT ACTIVATES

page 7 slide 14

Which receptor does melatonin have greater affinity for: MT1 or MT2

MT1

What pathway does MT1 activate?

MT1 and MT2 have overlap in pathways, either receptor can activate either pathway depending on cell type, downstream events are also cell dependent

What is the purpose of melatonin supplements

treat delayed sleep phase

How is melatonin reception affected by the blind

Circadian rhythm sleep disorders are in blind individuals

What are examples of melatonin receptor agonists?

Ramelteon is FDA approved binds to MT1 and MT2 receptors, prolonged release melatonin, agomelatine (discontinued in US due to liver toxicity), and tasimelteon (agonist for MT1 and MT2 receptors)