Pineal gland: A structural and functional enigma

Full text

Review Article
Pineal gland: A structural and functional enigma
Ashok Sahai
a,
*, Raj Kumari Sahai
b
a
Professor, Department of Anatomy, Dayalbagh Educational Institute (Deemed University), Dayalbagh, Agra, Uttar Pradesh 282 005, India
b
Senior Consultant, Department of Obstetrics and Gynaecology, Saran Ashram Hospital, Dayalbagh, Agra, Uttar Pradesh 282 005, India
article info
Article history:
Received 14 January 2013
Accepted 21 January 2014
Keywords:
Epiphysis cerebri
Pinealocytes
Corpora arenacea
Calcite crystals
Third eye
abstract
The structures and functions of neuroendocrine pineal gland remains an enigma to both
philosophers and scientists alike since time immemorial. Some of the structural and
functional mysteries of pineal gland are unfolded to some extent in this article by
reviewing the work of various researchers. Recently a neuronal circuit consisting of seven
neurons between retina and pineal gland have been established to relate the effect of light
and other rays on its secretion.
The various physical properties such as piezoelectricity, piezoluminescence, electro-
magnetic field, solar flare, infrared energy are also explained and correlated with the
structural and secretional components of the gland. The neurosecretion of pineal gland
such as melatonin play an important role in sleep-wake patterns, timings and release of
reproductive hormones along with temperature control.
The presence of all enzymes needed for the synthesis of di-methyl-tryptamine (DMT) in
pineal gland explains the near death experience (NDE) phenomenon. The various audio-
visual hallucinations in NDE phenomenon occur due to massive increase of DMT in pi-
neal gland before death. A very high concentration of di-methyl-tryptamine (DMT), pres-
ence of retinal proteins in 5e10% of pinealocytes, its role in thermoregulation and a
possible role as magnetoreceptor in blind men and highest deposits of fluoride in the body
are not only interesting but significant for the future research. Hence a lot of further
research on pineal gland is still required to correlate its unique properties with its struc-
tural components.
Copyright ª2014, Anatomical Society of India. Published by Reed Elsevier India Pvt. Ltd. All
rights reserved.
1. Introduction
The Pineal gland, a small piriform structure, shaped like cone
of the pine tree, is located above and behind the hind brain
(Fig. 1). The pineal gland for long has been regarded by the
biologists as the vestigial organ, like vermiform appendix in
the abdomen, with no functional importance and that it
degenerates with age is well approved. However, in the reli-
gious texts, both in the eastern and western philosophies it
has been regarded as the God organ, Pineal Eye, Third Eye, Eye
of Shiva, Eye of Dangma, etc. The pineal gland’s reference to
being the “Third Eye” is quite ironic, as if, the gland has a lens,
cornea and retina like actual eye. Galen named it as Konar-
eion. Herophellus (c 300 BC) noted that pineal gland was the
*Corresponding author. Tel.: þ91 9415395113.
E-mail address: ashoksahai2001@yahoo.co.in (A. Sahai).
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/jasi
journal of the anatomical society of india 62 (2013) 170e177
0003-2778/$ esee front matter Copyright ª2014, Anatomical Society of India. Published by Reed Elsevier India Pvt. Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jasi.2014.01.001

first gland to develop around 3rd week of intra uterine life
(IUL). Rene
´Descartes (1596e1650),
1
a French philosopher,
physiologist, physicist, mathematician and natural scientist
called it the “seat of the soul”, intimately associated with the
spiritual consciousness, intelligence etc.; this work was pub-
lished in 1662.
It was not until the 1958 that scientists determined its
function. Presence of photosensitive cells, synthesis of mela-
tonin, regulatory control on all the major endocrine glands,
modulation of sleep/wake patterns, seasonal functions
2,3
and
circadian rhythm, etc., lead to a large number of researches on
its developmental, histological, biochemical, evolutionary and
functional aspects. It is now confirmed to be a neuroendocrine
transducer of photic information into an endocrine response
through the synthesis and release of the hormone melatonin.
The pituitary gland which is regarded as the “master of the
endocrine orchestra” is lieutenant of the pineal gland.
2. Structural aspects
Keeping the human head in the “Frankfurt plane” (lower
border of orbit and upper margin of the external auditory
meatus lie in one horizontal plane), it is situated about
12.00 cm behind and a little above the root of nose in the
horizontal plane and about 5.00 cm deep to the skin and bone
of head in a coronal plane (vertical plane) passing just behind
the external acoustic meatus and about 5.00 cm above the
opening of the external ear. The gland is reddish grey in
colour, of the size of a rice grain, weighs a little above 0.1 g,
measuring 7.0 mm in length, 5.0 mm in width (transverse) and
3.0 mm in thickness (vertical). The MRI study of 249 patients
by Masayki Sumida et al (1996)
4
concluded that the size of
pineal gland increased until the age of 2 years and thereafter
remains stationary from 2 to 20 years of age. The gland is
geometrically placed in the midline.
5
Due to mineral deposits
that build up with age. The gland casts a radio-opaque shadow
in the radiographs, CT and MRI images of brain/head which is
a standard indicator of the midline position in the clinical
practice.
The gland has a rich blood supply; only next to the kidneys.
It is richly innervated by sympathetic and parasympathetic
nerve fibres. Sympathetic fibres are derived from the T1
segment of the spinal cord. The nerve fibres enter from the
dorsolateral aspect of the gland as the nervous conarii which
may be single or paired. Parasympathetic innervation comes
from the sphenopalatine and otic ganglia. In addition to
above, the gland has Central innervation by some nerve fibres
which penetrate the gland from the pineal stalk, which
probably originate in the paraventricular nucleus of hypo-
thalamus. Some neurons of trigeminal ganglia containing the
neuropeptide- PACAP also innervate the gland.
With the evolution of the photoreceptor element in the
pinealocyte cells, there has been a concomitant shift in the
neural connection of the pineal organ. The pinealofugal,
sensory innervation gave way to an autonomic, pinealopetal
motor innervation. Thus, direct photosensitivity was super-
seded by indirect, optically-mediated control of the now
secretory pineal gland. Pineal cytostructure seems to have
evolutionary similarities to the retinal cells of chordates.
6
Avian pineal glands are believed to act like the Suprachias-
matic nucleus (SCN) in mammals.
7
Microscopic examination in rats has revealed that the
pinealocytes are structurally analogous to the retinal cones,
lower order neurones and interstitial glial cells, indicating its
possible original function as an organ of sight.
8,9
The devel-
opment of cytoarchitecture reaches maturity by the middle of
first decade.
4
The pineal gland consists of a capsule and the
parenchyma. The parenchymal cells include: pinealocytes,
peptidergic neuron-like cells, pineal neurones and neuroglia
which includes the astrocytes, perivascular phagocyte, inter-
stitial cells and vascular endothelium. The pinealocytes or
chief cells (Fig. 2) account for about 95% of the cell population.
The pinealocytes are both light and dark type.
10
Each cell has a
polyhedral body and 4e6 long processes. They are highly
modified neurons arranged as cords and clusters. About 5e10%
pinealocytes have a selective group of retinal proteins.
11
The
cell processes, 4 to 6 in number are long with expanded ter-
minal buds. The buds end on the wall of the capillaries and on
the ventricular ependyma of the pineal recess. Besides other
organelles the terminal buds also contain polypeptide hor-
mones, the monoamines and gama-aminobutyric acid which
is a neurotransmitter. The major function of the pinealocytes
is synthesis and secretion of the melatonin.
9
Minute blood vessels enter the pineal gland through the
trabeculae and form a network of fenestrated capillaries.
They are closely related to the terminal buttons of the cell
processes of pinealocytes. Various secretions of pinealocytes
are discharged in the blood stream and also various amino
acids and other substances required for the synthesis of pi-
neal hormones etc., are taken up by the pinealocytes through
this route. There are no blood-brain-barriers in the pineal
gland.
12
The pineal gland is the locus of one of the circum-
ventricular organs; the ependyma of the pineal recess is lined
by modified ependymal cells, the tanycytes (tall, columnar,
ciliated cells), for to and fro transport of neurochemicals in
CSF.
Fig. 1 eMRI of head in the lateral view showing the
location of the pineal gland. Source: Frank Gaillard, in
Radiopaedia.org. September 19, 2010.
journal of the anatomical society of india 62 (2013) 170e177 171

The salts of calcium, magnesium, phosphorus, ammo-
nium, aluminium and fluoride are found. These minerals are
generally scattered in the extracellular matrix but often pre-
sent as lamellated concentric calcareous deposits (Fig. 3)
which are differently known as corpora arenacea, acervulus,
psammoma bodies or brain sand.
13
They were earlier
considered to be signs of ageing and degeneration. But
Baconnier et al (2002)
14
described presence of calcite form of
calcium carbonate in the normal pineal matrix.
Jennifer Luke (1997),
15
a British scientist, from the Univer-
sity of Surrey in England reported that the pineal gland is the
prime target of the fluoride accumulation. Later her landmark
study was substantiated by the similar reports.
16
Later it was
discovered that the fluoride accumulation was strikingly high
in the pineal gland.
17
In the same study Luke also reported
that soft part (noncalcified) of the gland has a fluoride level of
approximately 300 ppm while the hard part had a level of
approximately 21,000 ppm. The magnetic forces attract the
fluoride to the pineal gland. The impact of this accumulation
is not yet fully understood. The available evidences suggest
that the presence of fluoride reduces the melatonin levels and
shortens the time to puberty.
15
Based on this and other evi-
dences the National Research Council (USA) in 2006 declared
that the fluoride is likely to cause decreased pineal function.
18
A new form of bio-mineralisation has been studied in the
human pineal gland using Scanning Electron Microscopy
(SEM) and Energy Dispersive Spectroscopy (Debbie Edwards).
The calcification of the pineal gland which is typical in
adults has been reported in children as young as 2 years. The
calcification occurs at any age
19
; but the amount of calcifica-
tion is relatively independent of age.
20
There is microscopic
evidence of an intimate association between the calcification
and cellular membranes.
13
The calcified deposits are chemi-
cally similar to bone minerals
21
where they are known as
hydroxyapatite crystals. The calcification rates vary widely
from country to country, occurring in an estimated 40% of
Americans by the age of 17 years.
5
Some recent studies have
shown that the pineal calcification is significantly higher in
Alzheimer’s disease.
22
Researches suggest that the calcified
deposits in the pineal gland are associated with decreased
number of functioning pinealocytes and reduced melatonin
production
23
as well as impairment in sleep-wake cycle.
24
The
decline in melatonin has been suggested to be a trigger for the
ageing process.
3. Functional aspects
Of various endocrine organs, the functions of the pineal gland
were the last to be discovered. In the past any scientific
enquiry of the Pineal gland was consciously avoided because
of its association with various “Spiritual Phenomena”. In 1917
it was known that the extract of cow pineal lightened the
colour of frog skin. As yet the secretory activity of the gland is
only partially understood. The functions of the gland are
regulated by light and dark. The gland produces a number of
hormones which are released both in blood and cerebro-
spinal-fluid (CSF). The release of secretions requires sympa-
thetic stimulation. The known functions of the gland include:
➢Synthesis and secretion of indolamines group of hormones
viz., Melatonin, Serotonin, 5-Hydroxytriptamine, Norepi-
nephrine and tryptophan.
Fig. 3 eHistological picture of pineal parenchyma showing
minerals present as lamellated concentric calcareous
deposits known as corpora arenacea. Source: Koshy S and
Vettivel SK, J Anat Soc Ind 50(1):1e6.
Fig. 2 eHistological picture of the pineal gland in high
magnification (3100) showing Pinealocytes arranged in
cords and blood capillaries. Source: www.Lab.anhb.uwa.
au/school of Anatomy and Human Biology/The University
of Western Australia.
journal of the anatomical society of india 62 (2013) 170e177172

➢Synthesis and secretion of peptide group of hormones.
These hormones exert inhibitory influence on the pitui-
tary, thyroid, parathyroid, adrenal cortex, adrenal medulla,
ovary, testis and endocrine pancreas.
➢Synthesis of a psychoactive chemical di-methyl-trypt-
amine (DMT)
➢Pinoline, present in significant amount in the pineal pa-
renchyma is a betacarboline. It is a mono-amine oxidase
(MAO) inhibitor called (6-methoxy tetrahydro betacarbo-
line (6-Me OTHBC)) which acts on the GABA receptors. It is
known to magnify and prolong DMT effects. Pinoline is a
neuromodulator which prevents, amongst other effects,
the breakdown of serotonin. Pinoline is superior to Mela-
tonin in aiding DNA replication. Pinoline can make super-
conductive elements within the body. It encourages cell
division by resonating with the very pulse of life - 8 cycles
per second - the pulse DNA uses to replicate. This 8 Hz
resonance was measured in healers by Andrea Puharich in
the late 1970s.
➢About 5e10% of the pinealocytes have a selective group of
retinal proteins.
11
The lizard, frogs and birds use their pi-
neal glands to detect light. In a paper published in the
journal Neurochemical Research, RN Looley
25
wrote “.
That the pinealocytes have a selective group of retinal
proteins that are involved in the phototransduction
cascade”.
➢The pineal is a thermoregulatory organ.
26
The temperature
is up regulated by pineal gland and down regulated by the
Suprachiasmatic nucleus.
27
Aaron B Learner,
28
Professor of Dermatology and his co-
workers at Yale University (U.S.A) hoping that a substance
containing melatonin etc. from the pineal might be useful in
treating skin diseases, isolated and named the hormone as
melatonin in 1958 in a land mark research in Pineal physi-
ology. Their work was later published in 1960. The pineal is the
only gland in the body which converts serotonin into
melatonin. The melatonin production starts by the age of 3rd
month after birth and is inversely proportional to that of se-
rotonin. The levels rise during darkness reaching a peak level
of 300 pg/ml and fall during the day when the levels range
from undetectable amount to 20 pg/ml. To an average the
pineal gland produces <0.3 mg of melatonin per day. The
period of usual onset and rise of nocturnal elevation of
melatonin synthesis is not only sensitive to light but also to
the effect of the magnetic fields.
29,30
The known melatonin
mediated functions of Pineal gland include: regulating sleep-
wake patterns, strengthens body immune system, regulates
timing and release of female reproductive hormones, in fe-
males, regulates onset of menstrual cycle (menarche), cessa-
tion of menstrual cycles (menopause) and frequency &
duration of menstrual cycle, a powerful antioxidant prevent-
ing cellular damage. Therefore melatonin has become popular
in USA as the diet supplement, for lowering body temperature
and heart rate, for strengthening body immune system, and to
sense the direction (navigation tool) in blinds.
The abundant melatonin levels in the children are believed
to inhibit the sexual development and the pineal tumours
have been linked with precocious puberty. As the child
reached closer to puberty the melatonin levels start falling.
Similarly pinealectomy is known to result into precocious
puberty.
The Suprachiasmatic nucleus (SCN) in the anterior hypo-
thalamus uses a combination of daytime inhibitory and night-
time stimulatory signals to control the daily rhythm of pineal
melatonin synthesis.
31,32
At night the sympathetic neuro-
transmitter norepinephrine (NE) is released from the post-
ganglionic nerve terminals innervating the pineal gland, thus
stimulating b1 and a1 adrenoreceptors on the pinealocytes.
33
The Melatonin also acts as a chronobiotic molecule,
34
stabi-
lizing or re-enforcing the circadian rhythm of body functions
in mammals like rodents.
35
The gland acts as an intrinsic time
clock in the human body and regulates the circadian rhythm,
evaluation of length of Day and Night, calculation of correct
season to mate and turning up the sex drive. But many sci-
entists believe that in the human beings the hypothalamus
has taken this control and that the intrinsic rhythmicity of an
endogenous circadian oscillator in the suprachiasmatic nu-
cleus governs cyclical pineal behaviour.
There are a large number of environmental stresses which
affect the pineal function, such as unusual light and dark
rhythms, radiation, electromagnetic fields, sound, infrared
radiations, nutritional imbalance, temperature swings, high
altitude and over all daily stress.
Strassman (2001)
36
demonstrated synthesis of a psychoac-
tive chemical di-methyl-tryptamine, DMT in the pineal gland.
In an earlier study conducted by him
37
he proposed the theory
that the DMT could be the “Spirit molecule”. He hypothesised
that there is a massive release of DMT from the pineal gland
close to death and causes a near death experience (NDE), a
phenomenon which is both auditory and/or visual. It was also
demonstrated that DMT production is stimulated, in the
extraordinary conditions of birth, sexual ecstasy, childbirth,
extreme physical stress, near-death, and death, as well as
meditation.
36
4. Recent advances
4.1. Neuronal circuits of pineal phototransduction
The pineal gland has rich network of sympathetic, para-
sympathetic and some non-myelinated fibres from CNS and
trigeminal ganglia.
In the human beings this neuronal circuit is multi neuron
pathway.According to Standering (2008)
38
the 1st order neurons
starts from theGlial cells (non-image forming cells) found in the
8th layer of retina. The light signals from the retina reach the
suprachiasmatic nucleus (SCN) of the hypothalamus via retino-
hypothalamic tract. The 2nd order neurons carry the impulse to
the reticular formation of brain stem. From there the 3rd order
neurons descend as reticulospinal tract to the T-1 to T-3 spinal
cord and endin the neurons of the lateral column.The 4th order
neurons starting from the lateral column of T-1 come out from
the ventral root of first thoracic spinal nerves (T1) and ascend in
the cervical sympathetic chain to relay in the superior cervical
ganglion. The 5th order neurons come out of this ganglion and
ascend as a plexus around the internal carotid artery and its
branches.The sympathetic nerve fibres finally leave the medial
posterior choroidal arteries as nervous conarii to enter the
journal of the anatomical society of india 62 (2013) 170e177 173

pineal gland from its posterior aspect. However, Singh (2006)
39
describe that the 5th order neurons in the nervous conarii
enter the habenular nucleus and via habenulo-pineal tract. The
6th order neurons from the nucleus terminate in the ganglion
conariiplaced on the apex of thepineal gland and fromthere the
fibres of the 7th order neurons enter thesubstance of the pineal
gland.
Axelrod (1970) suggested an alternative neuron circuit and
opined that the light signals reaching SCN travel via para-
ventricular nucleus (PVN) which relay the circadian signals to
the spinal cord.
40
Thereafter these signals come out via sym-
pathetic system to the superior cervical ganglia (SCG), and
from there into the pineal gland. In the lower mammals the
signals from the paraventricular nucleus reach directly to the
Pineal gland via central innervation of the gland. However, in
the human beings this path has not been reported so far.
4.2. Piezoelectricity in the pineal gland
Piezoelectricity is the electric charge that accumulates in
certain solid materials, such as crystals, certain ceramics,
bone,
41
DNA and various proteins in response to the applied
mechanical stress.
42
The word piezoelectricity generally
means electricity resulting from pressure. In the direct
piezoelectric effect, an electric stress gives rise to voltage; in
converse, an applied voltage results in the elastic strain. Ac-
cording to Cady (1964)
43
if the pineal calcifications were
piezoelectric they could produce a surface charge distribution
and a strain by virtue of the interaction of the direct and the
converse piezoelectric effects whenever a subject was
exposed to an appropriate electromagnetic (EM) radiation.
Published in the Bioelectromagnetics Journal, S.S. Bacon-
nier (2002)
14
dissected 20 human pineal glands soon after death
and reported 100 to 300, micro-crystals per cubic millimetre.
He also observed that these micro-crystals were composed of a
mineral called calcite. These crystals were hexagonal in shape,
found floating inside the pineal glands and were very similar to
the crystals found in the internal ear known as otoconia
(otolith crystals). These crystals consist of calcium, carbon and
oxygen; expand and contract due to the presence of electro-
magnetic fields converting it into photons. David Wilcock
44
in
his book The Source Field Investigations mentioned that the
calcite micro-crystals could be responsible for an electrome-
chanical biological transduction mechanism in the pineal
gland, due to their structure and piezoelectric properties. Way
back in 1957 Nye,
45
with the help of the results of second har-
monic generation (SHG), demonstrated that the pineal gland
contained noncentrosymmetric material which according to
the crystallography symmetry considerations is piezoelectric.
A positive SHG response in his study was a proof of the pres-
ence of piezoelectric crystals.
In a significant multicentric study Sidney B. Lang with his
co-workers (1996)
16
from Israel and USA working on the pineal
gland of cadavers demonstrated that the piezoelectric crystals
were detected throughout the pineal gland; the distribution
and size of the crystals considerably varied. The hard part of
the gland, however, possessed hydroxyapatite crystals. They
identified three classes of crystals in the pineal parenchyma
(a) mulberry-like, (b) non mulberry-like and (c) non calcium
containing crystals.
The classical methods for measuring piezoelectricity
43,46
are not suitable for examination of specimens containing
small piezoelectric crystals dispersed in the nonpiezoelectric
material therefore an alternative technique that would detect
noncentrosymmetryeSecond Harmonic Generation (SHG)
16
as suggested by Dougherty and Kurtz (1976)
47
and Kurtz and
Dougherty (1978).
48
It has been observed that the piezoelectric property in
calcite micro-crystals is in the frequency range of mobile
communications. These crystals are capable of tuning into
radio stations without the use of electricity. Piezoelectric
crystals are used to turn sound vibrations into electrical cur-
rent. The researches have shown that the cell phone use and
other microwave emitting devices have an adverse effect on
the pineal gland by changing the way piezoelectric crystals in
human pineal gland function by interrupting the synthesises
the melatonin.
The presence of calcite micro-crystals, their contraction
and expansion in the presence of electromagnetic field and
piezoelectric property may go well with the hypothesis of
Gottfried de Purucker (2011)
49
published in the book ‘Man in
Evolution’ in which the author mentions that “whenever we
have a hunch, the pineal gland is vibrating gently; when we have an
intuition, or an inspiration, or a sudden flash of intuitive under-
standing, it vibrates more strongly though still gently.”
4.3. Piezoluminescence and the pineal gland
The piezoluminescence is emission of light created by pres-
sure upon certain solids. According to Atari (1982)
50
it is
characterised by recombination of processes involving elec-
trons, holes and impurity ion centres. The calcite micro-
crystals in the pineal gland give off light; the phenomenon is
known as piezoluminescence. The light produced is a cold
light viz., light without heat, ranging in the blue-green light
spectrum. A similar phenomenon occurs in certain marine
animals in the deep sea and some insects. The DMT and
tryptophan, found in high concentration in the human pineal
also have piezoluminescent qualities.
51
The classical picture
depicting the pineal gland as the centre for spiritual and
psychic energy and piezoluminescence is most widely used in
most of the monographs on pineal gland.
4.4. Electromagnetic field and the pineal gland
The human beings are surrounded by 60 Hz electrical fields in
our homes, work and outside where power lines tower over
almost every street.
52
The electromagnetic field (EMF) sup-
presses the activity of the pineal gland and reduces the
melatonin production, but the process which converts the
electromagnetic signals to chemical ones which regulate
melatonin synthesising gene regulation is not known.
42
James
et al, (1999)
52
opined that there is no escape from this except to
flee to a remote place, discretely or unpopulated area. But
even there the pineal gland could be under siege.
The pineal gland contains magnetic material in birds and
other mammals. In birds the gland, being magnetorecepter
helps to align the body in space. It works as centre for navi-
gation which may be the case in blind men too.
journal of the anatomical society of india 62 (2013) 170e177174

In a significant study conducted on 7 male volunteers (aged
16e22 years) at the University of Dortmund, West Germany,
Grieffahn et al, (2002)
53
observed that different parts of the
electromagnetic spectrum (a) moderate bright light, (b) very
strong magnetic field and (c) Infrared radiation suppress, at
least partially, melatonin synthesis.
4.5. Solar flares and the pineal gland
Richard Carrington
54
observed a solar flare for the first time on
1 September 1859 projecting the image produced by an optical
telescope, without filters Fig. 4. These flares keep happening
very now and then in varying quantum and frequencies.
These flares produce radiation across the electromagnetic
spectrum. According to a study published in the New Scientist
back in 1998, there is a direct connection between the Sun’s
solar storms and human biological effects. These flares use
the same conduit to reach the earth as is used for the ordinary
solar radiations. Pineal gland in our brain is stimulated by the
increased electromagnetic activity during the solar flare
which causes the gland to produce excess melatonin.
4.6. Infrared energy and the pineal gland
Infrared energy waves, the lower frequency waves on the light
spectrum have longer wave length. They correspond with
lower emotional energies and moods. While the higher fre-
quency energy waves such as green, blue and violet range
produces higher emotional energies and moods. Result of
strong pulses of infrared energy waves on the brain and
especially the calcite micro-crystals in the pineal gland are (a)
Sleepiness, (b) Crying, (c) Agitation, (d) Depression, (e) Anxiety,
(f) Aggression, (g) Fear, (h) Terror, (i) Hopelessness, (j) Grief, (k)
Apathy and (l) Even death.
Studies on rodents
55
suggest that the pineal gland may
influence the actions of recreational drugs, such as cocaine
and antidepressants, such as fluoxetine.
56
4.7. Pineal gland and circadian rhythm
In the human beings the cells of retina, iris, skin and pine-
alocytespossess light-sensing capabilities. When thesecells are
cultured, they mark outan independent rhythm. It isthe roleof
the pineal gland and the hypothalamus to unite and manage
them correctlydlike a control tower for the biological clock.
Pinealectomy is reported to block photoperiodic responses
in all experimental mammals.
57
Surgical pinealectomy in rats
housed under a 12:12 lightedark cycle did not affect REM or
NREM
58
.In another study it was observed that although the
pinealectomised rats housed in constant darkness exhibited a
decrease in the amplitude of the circadian rhythm of REM and
NREM sleep.
59
In the retina of hamsters there is another centre for
melatonin metabolism indicating that the eyes have their own
built in circadian rhythm. The researchers are looking for
exact location of this clock in the human eye. They demon-
strated that the retinal clock could be set and reset even when
the SCN was destroyed. No one yet knows what this separate
clock is for or how it regulates the SCN.
5. Conclusions
Based on the review of structural and functional aspects
(piezoelectric, piezoluminescent and other electromagnetic
properties) of the Pineal Gland it is concluded that:
➢The gland is light sensitive and the phototransduction path
is multi neuronal.
➢The pineal hormones are up regulated in the dark and
down regulated in the light.
➢The pineal hormones regulate pituitary, thyroid, para-
thyroid, adrenal, ovary, testis, and endocrine pancreas.
The gland is thermoregulatory; regulates the sleep wake
cycles and sex pattern too.
➢Though it regulates the circadian rhythm in the lower
mammals but the same is doubtful in the human beings.
➢The presence of retinalproteins, itsevolutionary closeness to
the retina, presence of a separate circadian rhythm in the
retina, piezoelectric and piezoluminescent crystals in the
gland, sensitivity of pineal to the electromagnetic forces,
magnetoreceptor properties and its possible role as an in-
strumentof navigation in the blinds areinteresting and need
further probe.
Conflicts of interest
All authors have none to declare.
Acknowledgements
I most humbly acknowledge my supreme father, Prof. P. S.
Satsangi Saheb, the Chairman, Advisory Committee on
Fig. 4 eA photograph of Solar Flare Source: http://
portlandmaineacupuncture.com/the-effect-of-solar-flares-
on-our-pineal-gland/.
journal of the anatomical society of india 62 (2013) 170e177 175

Education, DEI, Dayalbagh, Agra, who gave me intuitive
guidance to write this article.
references
1. Descartes R. The passions of the soul. excerpted from. In:
Chalmers D, ed. Philosophy of the Mind. New York: Oxford
University Press, Inc; 2002.
2. Macchi M, Bruce J. Human pineal physiology and functional
significance of melatonin. Front Neuroendocrinol.
2004;25(3e4):177e195.
3. Arendt J, Skene DJ. Melatonin as a chronobiotic. Sleep Med Rev.
2005;9(1):25e39.
4. Sumida Masayuki, James Barkovich A, Hans Newton T.
Pediatric neuroradiology; pineal gland, magnetic resonance;
brain, anatomy. AJNR Am J Neuroradiol. 1996;17:233e236.
5. Zimmerman RA, Bilaniuk LT. Age-related Incidence of pineal
calcification detected by computed tomography. Radiology.
1982;142:659e662.
6. Klein D. The 2004 Aschoff/Pittendrigh lecture: theory of the
origin of the pineal glandda tale of conflict and resolution. J
Biol Rhythms. 2004;19(4):264e279.
7. Natesan A, Geetha L, Zatz M. Rhythm and soul in the avian
pineal. Cell Tissue Res. 2002;309(1):35e45.
8. Collins JP, Voisin P, Falco
´n J, et al. Pineal transducers in the
course of evolutions: molecular organisation, rhythmic
metabolic activity and role. Arch Histol Cytol. 1989;52:441e449.
9. Falco
´n J. Cellular circadian clocks in the pineal. Prog Neurobiol.
1999;58:121e162.
10. Koshy S, Vettivel SK. Varying appearances of calcification in
human pineal gland: a light microscopic study. J Anat Soc
India. 2001;50(1):01e06.
11. Beatriz M, Lopes MD. Endocrine Pathology. Springer;
2004:97e108.
12. Pritchard, Thomas C, Alloway KD. Medical Neurosciences.
Hayes Barton Press; 1999:76e77.
13. Welsh MG. Pineal calcification: structural and functional
aspects. Pineal Res Rev. 1985;3:41e68.
14. Baconnier S, Lang S, Polomska M, et al. Calcite microcrystals
in the pineal gland of the human brain: first physical and
chemical studies. Bioelectromagnetics. 2002;23(7):488e495.
15. Luke J. The Effect of Fluoride on the Physiology of the Pineal Gland.
Guildford: University of Surrey; 1997. Ph.D. Thesis.
16. Lang SB, Andrew A, Marino GB, et al. Bioelectrochem Bioenerg.
1996;41:191e195.
17. Luke J. Fluoride deposition in the aged human pineal gland.
Caries Res. 2001;35(2):125e128.
18. Mahlberg R, Kienast T, Ha
¨del S, et al, National Research
Council. Fluoride in Drinking Water: A Scientific Review of EPA’s
Standards. Washington D.C: The National Academies Press;
2006.
19. Scharemberg K, Liss L. The histologic structure of the human
pineal body. Prog Brain Res. 1965;10:193e217.
20. Tapp F, Huxley M. The histological appearance of the human
pineal gland from puberty to old age. J Pathol.
1972;108:137e144.
21. Mabie CP, Wallace BM. Optical, physical and chemical
properties of pineal gland calcifications. Calcif Tissue Res.
1974;16:59e71.
22. Mahlberg R, Walther S, Kalus P. Pineal calcification in
Alzheimer’s disease: an in vivo study using computed
tomography. Neurobiol Aging. 2009b;29(2):203e209.
23. Kunz D, Stephan S, Richard M, et al. A new concept for
melatonin deficit: on pineal calcification and melatonin
excretion. Neuropsychopharmacology. 1999;21(6):765e772.
24. Mahlberg R, Kienast T, Ha
¨del S, et al. Degree of pineal
calcification (DOC) is associated with polysomnographic sleep
measures in primary insomnia patients. Sleep Med.
2009c;10(4):439e445.
25. Lolley RN, Craft CM, Lee RH. Photoreceptors of the retina and
pinealocytes of the pineal gland share common components
of signal transduction. Neurochem Res. 1992;17(1):81e89.
26. Shimada SG. Pineal Gland and Temperature Regulation. John and
Pierce Laboratory Inc., National Institute of Health; 1985.
Project no. IR 23AM 05882.01.
27. Tong J, Qin LQ, Wang DJ. Mechanism of pineal and
suprachiasmatic regulation on circadian rhythm of body
temperature in rats. Space Med Med Eng (Beijing).
2002;13(2):101e103.
28. Lerner AB, Case JD, Takahashi Y. Isolation of melatonin and
5-methoxyindole-3-acetic acid from bovine pineal glands. J
Biol Chem. 1960;235:1992e1997.
29. Trinder J, Armstrong SM, O’Brien C. Inhibition of melatonin
secretion onset by low levels of illumination. J Sleep Res.
1996;5:77e82.
30. Wood AW, Armstrong SM, Sait ML, et al. Changes in human
plasma melatonin profiles in response to 50 Hz magnetic field
exposure. J Pineal Res. 1998;25:116e127.
31. Perreau-Lenz S, Kalsbeek A, Garidou ML, et al.
Suprachiasmatic control of melatonin synthesis in rats:
inhibitory and stimulatory mechanisms. Eur J Neurosci.
2003;17:221e228.
32. Perreau-Lenz S, Pe
´vet P, Buijs RM, et al. The biological clock:
the bodyguard of temporal homoeostasis. Chrobiol Int.
2004;21:1e25.
33. Fu H, Subramanian RR, Masters SC. 14-3-3 Proteins: structure,
function and regulation. Annu Rev Pharmacol Toxicol.
2000;40:617e647.
34. Pe
´vet P, Agez L, Bothorel B, et al. Melatonin in the multi-
oscillatory mammalian circadian world. Chronobiol Int.
2006;23:39e51.
35. Armstrong SM. Melatonin: the internal zeitgeber of
mammals. Pineal Res. 1989;7:157e202.
36. Strassman RJ. DMT: The Spirit Molecule. A Doctor’s Revolutionary
Research into the Biology of Near-Death and Mystical Experiences.
2001. Rochester, Vt: Park Street.
37. Strassman RJ. The pineal gland. In: Lyttle Thom, ed.
Psychedelic Monographs & Essays. vol. 5. Boynton Beach,
Florida: PM & E Publishing Group; 1990.
38. Standering S. Ventricular system & subarachnoid space”,
chapter 10, pp. 240e241, “Diencephalon”, chapter 21, p.
324, “The nervous system” chapter 24, p. 380, Eye, chapter
40, p. 692. In: Gray’s Anatomy: The Anatomical Basis of
Clinical Practice. 40th ed. Churchill Livingstone: Elsevier;
2008.
39. Inderbir Singh. Text Book of Human Neuroanatomy, Chapter 13,
Diencephalon eEpithalamus. 7th ed. New Delhi: JP Brothers;
2006:190e193.
40. Axelrod. The pineal gland. Endeavour. 1970;29(108):144e148.
41. Marino AA, Becker RO. Origin of the piezoelectric effect in
bone. Calcif Tissue Res. 1971;8:177e180.
42. Reiter RJ. Static and extremely low frequency electromagnetic
field exposure: reported effects on the circadian production of
melatonin. J Cell Biochem. 1993;51:394e403.
43. Cady WG. Piezoelectricity. New York: Dover; 1964.
44. David Wilcock. The Source Field Investigations: Kind Body
Spirit.me. The Hidden Science and Lost Civilizations Behind the
journal of the anatomical society of india 62 (2013) 170e177176

2012 Prophecies. Souvenier Press. Book released on 31 July
2012.
45. Nye JF. Physical Properties of Crystals. Oxford: Clarendon Press;
1957.
46. Giebe E, Scheibe A. The growth and properties of piezoelectric
bismuth germanium oxide. Z Phys. 1925;33:760.
47. Dougherty JP, Kurtz SK. A second harmonic analyzer for the
detection of non-centrosymmetry. J Appl Crystallogr.
1976;9:145e158.
48. Kurtz S, Kand JP, Dougherty. Methods for the detection of
noncentrosymmetry in solids. Syst Mater Anal.
1978;4:269e342.
49. de Purucker G. Man in Evolution, Chapter 16 eThe Pineal and
Pituitary Glands. Theosophical University Press; 2011:208.
50. Atari NA. Piezoluminiscence phenomenon. Phys Lett.
1982;90(1e2):93e96.
51. Steen HB. On the Luminescence of L-tryptophane and L-tyrosine in
Aqueous Solution at 77dk Induced by X-rays and UVelight. 1967.
52. Burch James B, Reif John S, Yost Michael G, et al. Reduced
excretion of a melatonin metabolite in workers exposed to
60 Hz magnetic fields. Am J Epidemiol. 1999;150:27e36.
53. Grieffahn B, Kunemund C, Blaszkewicz M, et al. Effects of
electromagnetic radiation (bright light, extremely low
frequency magnetic fields, infrared radiations) on the
circadian rhythm of melatonin synthesis, rectal temperature
and heart rate. Ind Health. 2002;40:320e327.
54. Carrington RC. Description of a singular appearance seen in
the sun on September 1, 1859. Mon Not R Astron Soc.
1859;20:13e15.
55. Akhisaroglu M, Ahmed R, Manev H. The pineal gland is
critical for circadian Period1 expression in the striatum and
for circadian cocaine sensitization in mice.
Neuropsychopharmacology. 2003;28(12):2117e2123.
56. Dimitrijevic N, Akhisaroglu M, Imbesi M, et al. The pineal
gland and anxiogenic-like action of fluoxetine in mice.
Neuroreport. 2004;15(4):691e694.
57. Hazlerigg DG, Wagner GC. Seasonal photoperiodism in
vertebrates: from coincidence to amplitude. Trends Endocrinol
Metab. 2006;17:83e91.
58. Rechtschaffen A, Whitehead WE, Whitehead PK, et al. Role of
the pineal gland in light-off triggering of paradoxical sleep in
the rat. Psychophysiology. 1969;6:272.
59. Kawakami M, Yamaoka S, Yamaguchi T. Influence of light
and hormones upon circadian rhythm of EEG slow wave and
paradoxical sleep. In: Itoh S, Ogata K, Yoshimura H, eds.
Advances in Climatic Physiology. Tokyo, Japan: Igaku Shoin;
1972:349e366.
journal of the anatomical society of india 62 (2013) 170e177 177