Hormone menubar
GSE
MELATONIN Production
MELATONIN productionWhere is
MELATONIN produced?
Pineal Gland
MELATONIN
is produced and secreted by the pineal gland under control of the hypothalamus
mainly when it is dark.
Light / dark
status is provided by the hypothalamic "Master Clock"
The Biological
Clock
A pea-sized,
pinecone-shaped organ located in the exact center of the brain -
this gland is the first to form during human fetal development, being clearly
distinguishable a mere three weeks after conception. Composed
of pinealocytes (pineal cells).
With a rich supply of adrenergic nerve fibers that influence its secretions.
MELATONIN
is the only hormone secreted by the pineal gland. Secreted
by pineal parenchymal cells into the general circulation and
into the cerebrospinal fluid MELATONIN is an indoleamine compound,
derived from the amino acid tryptophan, with SEROTONIN
being its immediate precursor. MELATONIN
was discovered when it was found to lighten amphibian skin.
MELATONIN
secretion is regulated by sympathetic nervous System (SNS), increased in response
to darkness . Tightly controlled by the hypothalamic
circadian pacemaker ("Master biological clock"),
MELATONIN thus provides a hormonal
signal of night-time darkness; MELATONIN
secretion is also increased in response to hypoglycemia.MELATONIN
is not stored We cannot rely on yesterday's
MELATONIN for today; MELATONIN each evening
Retina, Lens, GI tract, skin +
MELATONIN
can also be produced directly by the retina, lens, GI tract, skin and other
tissues/cells (E.g. bone marrow
cells, lymphocytes and epithelial cells). These are NOT regulated by light/dark.
T hese cells do not directly
release MELATONIN
into the blood, but act on local target cells
MELATONIN
produced by enterochromaffin cells of the GI mucosa represents the most important
extra-pineal source of MELATONIN.
T he GI tract
contains ~400 times the amount
of the pineal gland MELATONIN enters circulation, where it has an indirect, but profound, protective effect on
the GI tract and organs via the brain-gut axis. MELATONIN affects GI motility, is protective of duodenal epithelium
and pancreas, prevents GERD and ulcers, and much more
MELATONIN
Health Benefits
What affects
MELATONIN production
/ secretion?
Pineal/retinal MELATONIN
production Inhibited by light and
permitted by darkness
Light/dark
MELATONIN
production
:
MELATONIN production
decreases with age
Fetal / Baby
MELATONIN
Levels
Early in pregnancy.
MELATONIN -binding
sites are created in the suprachiasmatic nucleus (SCN) in the hypothalamus
of the developing brain. Maternal MELATONIN
crosses the placenta and can synchronize the fetal biological clock.
Daily MELATONIN rhythm in milk
could take over for newborn .Shortly after birth.
Very little MELATONIN
is detectable in body fluids, and although the circadian rhythm of
MELATONIN does not exist at birth,
it appears at 9-12 weeks of age and is fully established by 5-6 months of
age.
Young child.
Nighttime
levels reach a peak in children between on average 3 to 5 (another source says 1-3)
years of age (may explain their tendency to sleep longer than adults) and decrease
steadily throughout puberty. The abundant
MELATONIN levels in children are believed
to inhibit sexual development.
Puberty.
By
the end of puberty, peak MELATONIN
levels have decreased significantly.
Adult. Levels continue
to fall steadily throughout adult life.
Old age. Lower levels
are seen in old age.
Circadian profiles of serum
MELATONIN concentrations at various ages
Gray area=Darkness.
MELATONIN production
lowered by blue lightDr. George Brainard experimented on 600 healthy
volunteers
Blue light
significantly lowered MELATONIN production.
Studies at 2:00 am (when
MELATONIN levels at peak) exposed dilated
pupils to different wavelengths of monochromatic light (only one color) over 90
minutes, found that the short wavelength in the blue portion of the visible
spectrum was most potent at lowering MELATONIN
production. Special
retinal photoreceptor regulates MELATONIN
production.
It was revealed that it is not the visual rod and cone photoreceptor
mechanism of the eye that is regulating pineal
MELATONIN production, but that a novel
photoreceptor in the retina was responsible. Only 0.5-1.7 foot-candles of blue-green
light (509nm) and 10 foot-candles of broad-band white light can lower
MELATONIN production under tightly
controlled exposure conditions.
MELATONIN production lowered
by fluoride
The pineal gland calcifies over time as a consequence
of incorporating fluoride. During the late
1990's, scientist Jennifer Luke of the University of Surrey, England, was the first
to study of the effects of sodium fluoride on the pineal gland. She determined
that the pineal gland was a target for fluoride, absorbing more fluoride than any
other physical matter in the body, even bones
The result of 50 years of prophylactic fluorides
in dentistry is that the aged pineal contains more fluoride than any other normal
soft tissue. Significantly higher than in muscle.
In terms of mineralized tissue, the mean fluoride concentration in the pineal calcification
was equivalent to that in severely fluorosed bone and more than 4x higher than in
corresponding bone ash,
Given
the pineal gland's importance to the endocrine system, its calcification would block
endocrine activity. Providing an explanation of
the physiological damage caused by sodium fluoride. Fortunately, a fluoride
calcified pineal gland can be stimulated by frequent exposure to outdoor sunshine
Anti-anxiety drugs suppress
MELATONIN
Valium and Xanax
(benzodiazepine drugs) shown to suppress
MELATONIN and disrupt sleep patterns in humans
and rodents. Both cause decreased production of
MELATONIN at night. In a study from
the Niigata College of Pharmacy in Japan, Valium also inhibited N-acetylserotonin
(NAS) and N-acetyltransferase (NAT), enzymes necessary for
MELATONIN synthesis in the pineal gland.
(See below)
Other factors promoting production:
Vitamins B6, B12, folate (synthesis cofactors of SAMe), Vitamin B3 Acetyl carnitine - acetylated form of L-carnitine;Hypoglycemia; Tryptophan - MELATONIN's protein amino acid precursor;SSRIs (anti-depressants);Exercise (except late evening exercise
Other factors inhibiting production
Fluoride - MELATONIN production lowered by fluorideAlcohol; Caffeine; Late evening exercise -
during MELATONIN rising phase; [Wiley ]Estrogen -
Direct exposure to ESTRADIOL reduced α1
/ β-adrenoceptor-induced
stimulation of MELATONIN synthesis and release.
[PubMed ]NSAIDS (Non-steroidal anti-inflammatoru drugs) - E.g. aspirin,
Ibuprofen;Beta blockers - keep MELATONIN
levels
from rising naturally at night; See: β-blockers
- Like leaving the light on all night Calcium-channel blockers; Diuretics;
MELATONIN synthesis pathway
in the bodyPineal and retinal
SEROTONIN (5-HT)
synthesis is up-regulated at night controlled by ß-adrenergic signaling.
Sympathetic nerves from the superior cervical ganglion
(SCG) SEROTONIN synthesis
is due to increased protein expression of tryptophan hydroxylase (TPH), the rate-limiting
enzyme of SEROTONIN
synthesis.
Circadian 5-HT pineal production regulated by adrenergic signaling .
Pineal 5-HT production
displays a tri-phasic diurnal pattern, continuing in constant darkness
and influenced by light intrusion at night.
SEROTONIN content in the pineal
gland is higher than in any other part of the body.
(i) During
the day - Pineal
5-HT levels
constant and high
(ii) Early
in the night (just after the lights are off) - Sharp rise
in pineal 5-HT
synthesis and release MELATONIN synthesis.
(iii) Late
in the night -
5-HT levels
are low, as 5-HT
is used to make MELATONIN
. However, in the absence of
MELATONIN release, pineal
5-HT can reach twice daily levels.
Diurnal variation in
MELATONIN synthesis is brought about
by NOREPINEPHRINE (NE). Secreted by the postganglionic
sympathetic nerves (the superior cervical ganglion/SCG) that innervate the pineal
gland. NE interacts with ß1-adrenoreceptors on the surface of the pinealocytes
(pineal cells) to increase pineal cAMP, which in turn activate the N -acetyltransferase
(NAT) required for MELATONIN
synthesis in the biosynthesis pathway, converting tryptophan to
MELATONIN .
Enzyme
Converts to:
1
TPH (tryptophan hydroxylase)
(vitamin B3-dependent enzyme**)
Tryptophan→ 5-HTP
2
AADC (aromatic amino acid decarboxylase)
(Aka 5-HTP decarboxylase)
(vitamin B6-dependent enzyme)
5-HTP → SEROTONIN
(5-HT / 5-hydroxytryptamine)
3
NAT (Serotonin N-acetyl transferase)
SEROTONIN → NAS
(N-acetylSEROTONIN)
4
HIOMT (hydroxyindole-O methyltransferase)
+ SAMe (Donatesmethyl group CH3
to HIOMT )
(methionine, vitamins B6, B12, folate
dependent)
SAMe -And Other Methyl Donor Molecules
NAS → MELATONIN
** The body often uses Tryptophan to make vitamin B3, at a very
high cost of 60mg L-Tryptophan to make just 1 mg B3.
SAMe
(a methyl donor molecule made from the amino acid methionine and
ATP)
is essential for MELATONIN
and
SEROTONIN
production
SAMe
is the daytime equivalent of
MELATONIN - and like
MELATONIN, it is produced under control
of the master biological clock; Natural
synthesis o f MELATONIN (and
SEROTONIN)
depends on adequate SAMe
synthesis during the day -
SAMe donates a methyl group
molecule (CH3 ) to the enzyme HIOMT that converts the acetylated form
of SEROTONIN (NAS) to
MELATONIN; Vitamins
B6, B12 and folate (folic acid)
are essential cofactors of
SAMe production At night
MELATONIN ▲ ▲ ▲
/ SAMe ▼ ▼ ▼
and in the day
SAMe ▲ ▲ ▲
/ MELATONIN▼ ▼ ▼
- SEROTONIN
is also produced at night.
SAMe -And Other Methyl Donor Molecules
