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Pineal Gland

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Raja N. L.

Khan Womens’ College (Autonomous)


Zoology (H), 6th SEM, Paper DSE3T-Endocrinology
by M. Malik Mukherjee
Pineal Gland
Study areas:
A. Structure of Pineal Gland,
B. Secretion of Pineal Gland,
C. Functions- In Biological Rhythms & Reproduction.

Pineal Gland Essentials-

• Of the endocrine organs, the function of the pineal gland was the last discovered.
• Located deep in the center of the brain, the pineal gland was once known as the “third eye.”
• The pineal gland produces melatonin, which helps maintain circadian rhythm and regulate
reproductive hormones.

A. Structure of Pineal Gland:

Anatomy
The epiphysis cerebri or pineal gland is a reddish-grey,
approximately 5 – 8 mm long, pine cone-like structure that is
located in the diencephalic part of the prosencephalon
(forebrain). The gland was formed as an outward growth of the
roof of the third ventricle. Therefore, the gland rests between the
posterior aspects of the thalami as it projects posteriorly from the
wall of the third ventricle.

Its attachment to either half of the brain is by the


Habenular commissure and trigone superiorly, and the posterior
commissure inferiorly. The Habenular and posterior commissures
are a part of the pineal stalk. The Habenular commissure is a part
of the superior lamina of the stalk, while the posterior
commissure is a part of the inferior lamina. The space between
the laminae is known as the pineal recess. It communicates
anteriorly with the hypothalamic sulcus and the third ventricle.

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It has two essential components one is hormone-producing cells called Pinealocytes,
and the other is supporting cells that transmit information called glial cells.

The pineal gland often appears calcified in x-rays, which is usually due to fluoride,
calcium, and phosphorus deposits that build up with age.

Histology
The pineal gland is encased by pia mater and lobulated by its connective tissue septae
that projects into the gland. Within the epiphysis cerebri, there are pinealocytes and neuroglia
cells.

The pinealocytes account for approximately 95% of the cellular content of the gland.
They are irregularly shaped with peripheral processes, and lightly staining large round nuclei.
Pinealocytes are primarily concerned with the photo-regulated production of melatonin. This
hormone works with the body’s circadian rhythm (which is controlled by the suprachiasmatic
nucleus of the hypothalamus) to regulate the cycle of sleep and wakefulness. Additionally,
some researchers believe that melatonin may alter sexual development in humans, contribute
to thermoregulation, and cellular metabolism.

There are also the corpora arenacea (brain sand) bodies present within the gland.
Calcification of these bodies is a common occurrence with increasing age. As a result, they
appear as radiographic opacities on plain film radiography and can, therefore, be used as
landmarks.

Vascular supply
Posterior medial choroidal artery provides the pineal gland with oxygenated blood
and the internal cerebral veins drain deoxygenated blood from the pineal gland.

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B. Secretion of Pineal Gland:
The pineal gland secretes a single hormone—melatonin (not to be confused with the
pigment melanin). This simple hormone is special because its secretion is dictated by light.
Researchers have determined that melatonin has two primary functions in humans—to help
control your circadian (or biological) rhythm and regulate certain reproductive hormones.

C. Functions-
a) In Biological Rhythms:
Melatonin is a major natural hormone made in the mammalian pineal gland (
Extrapineal tissues such as the retina, harderian glands, and gastrointestinal tract also
synthesize the hormone but to a lesser extent). The melatonin-generating system is
characterized by three basic features including photosensitivity, diurnal (circadian)
rhythmicity (highest levels produced at night in darkness) and age-related decrease in its
activity.
Before we start, let’s have a look on sleep. Based on characteristic polysomnography
signals, sleep has been divided into two distinct states known as rapid eye movement (REM)
and non‐rapid eye movement (NREM) that alternate in a periodic manner throughout the night.
NREM sleep characterized by the presence of a minimum of 20% high voltage low frequency
cortical δ waves (ranging from 0.5–2 Hz known as NREM 3) is also termed slow wave sleep
(SWS) or deep sleep and provides an indication of the intensity or depth of sleep.
The circadian oscillator is located in the suprachiasmatic nucleus (SCN) of the anterior
hypothalamus. It is the primary source of rhythmic temporal information (circadian
pacemaker) for all physiologic processes including the modulations of sleep and wakefulness.
The period, or frequency, of oscillation of the central circadian pacemaker is relatively
insensitive to external and internal environmental influences.
Melatonin is an important physiological sleep regulator in diurnal species including
humans. The sharp increase in sleep propensity at night usually occurs 2 h after the onset of
endogenous melatonin production in humans; in addition, the duration of nocturnal melatonin
relays night length information to the brain and various organs, including the SCN itself. The
circadian melatonin rhythm is closely associated with the sleep rhythm in both normal and
blind subjects. In humans and other diurnal species, melatonin acts at the SCN to attenuate the
wake‐promoting signal of the circadian clock, thus promoting sleep. In addition, melatonin
acts at the default mode network (DMN) regions in the brain to promote fatigue and sleep‐like
changes in activation of the precuneus. The DMN is a network of brain regions that is active
during rest in the absence of task‐dependent performance. While asleep, connectivity within
the DMN decreases and is diminished during SWS.

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Melatonin has been reported to enhance sleep in rats, young chickens, and humans. In
humans, for example, an intravenous bedtime dose of 50 mg reduced sleep latency, whereas
three oral daytime doses of 80 mg enhanced sleepiness. On the other hand, no effect (except
prolongation of REM sleep latency after the large dose) was reported following a 1 mg or 5
mg oral dose administrated at bedtime. Daily administration of 2 mg melatonin in the late
afternoon induced unusual tiredness in the early evening after 4 to 5 days and an increase in
plasma level that exceeded endogenous night time levels by a factor of 10 to 100. While it
appears unlikely that melatonin is directly involved in sleep regulation, owing to the extremely
large doses needed to alter sleep, it does appear that it may affect sleep indirectly by altering
the phase of the circadian pacemaker. Melatonin may provide the first pharmacologic means
of shifting the phase position of the circadian rhythm.
The production of melatonin generally decreases with age. Older subjects show an
increased lag from sunset to the onset of melatonin pulse and to the melatonin pulse peak and
between melatonin secretion peak and the middle of the sleep period. The apparent relationship
between increasing age, declining melatonin production and increasing insomnia prevalence
has led to the ‘melatonin replacement’ hypothesis, which suggests that replenishing the
deficiency in the endogenous sleep‐regulating hormone will improve sleep.

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b) In Reproduction:
There’s some evidence that light exposure and related melatonin levels may have an
effect on a woman’s menstrual cycle. Reduced amounts of melatonin may also play a role in
the development of irregular menstrual cycles.
i) The effect of melatonin on the onset of puberty

It has been reported that melatonin secretion has an inhibitory influence on the
hypothalamic secretion of GnRH in humans. It is therefore speculated that before puberty,
melatonin concentrations are too high thus inhibiting the hypothalamic activation. But prior to
puberty, the levels of melatonin decline below the threshold value thus forming the trigger
signals of GnRH from the hypothalamus which leads to the onset of pubertal changes.
Therefore, it is the decline of melatonin levels that trigger puberty. Studies have demonstrated
that high nocturnal melatonin secretion in children delays puberty whereas low levels of
melatonin have been shown to be associated with precocious puberty.

ii) The effect of melatonin in sexual maturation

Melatonin is involved in the control of pulsatile secretion of LH and that there is a


negative correlation between nocturnal melatonin and LH concentrations. Furthermore, high
levels of serum melatonin in women have been shown to be associated with amenorrhea
accompanied with decreased GnRH/LH pulsatile secretion. Similarly, increases in nocturnal
peak amplitude and duration of melatonin were reported in amenorrhoeic athletes who
displayed irregularities in hypothalamic-pituitary-ovarian-axis functioning. In vitro studies
have demonstrated that melatonin leads to the down-regulation of the GnRH gene expression
in a cell line containing GnRH secreting neurons.

iii) The effect of melatonin on testicular function

In animal studies, it has been shown that melatonin may modulate testicular function.
In mice and rats, it was reported that melatonin has an inhibitory effect on Leydig cells. The
Leydig cells are responsible for the production of testosterone. Mel 1a and Mel1b receptor
mRNAs are expressed in epithelial cells of rat epididymis suggesting that melatonin has a role
in the regulation of epididymal physiology. The epididymis is important for the maturation
and storage of spermatozoa before they are ejaculated into the female reproductive tract.

It has been also reported that, long term administration of melatonin to healthy men is
associated with decreased semen quality. Sperm concentration, motility as well as testosterone
levels were found to be significantly decreased in healthy men administered with melatonin.
On the other hand, an in vitro study demonstrated that administration of melatonin to human
spermatozoa improved progressive motility and reduced the number of static cells.

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iv) Effect of melatonin on ovary function

The melatonin is able to pass through all cell membranes and enter all tissues because
of its lipophilic property, however, it specifically concentrates in the ovary. Studies have
shown that high levels of melatonin are found in human preovulatory follicular fluid at
concentrations which are much higher than those in serum. Larger the follicle the higher is
melatonin concentration.

The ability of melatonin to promote embryo development in different species has


correspondingly been reported. When mouse embryos were cultured in medium containing
melatonin, increased blastocyst development rates were observed. This suggests that
melatonin may be involved in embryo development.

Melatonin, secreted by the pineal gland, has been reported to be taken up into the
follicular fluid from the blood. The free radicals produced within the follicles, especially
during the ovulation process, are scavenged by melatonin, and reduced oxidative stress may
be involved in oocyte maturation and embryo development. Evidence is pointing to the fact
that melatonin treatment for infertility in women increases intra-follicular melatonin
concentrations which subsequently reduces intra-follicular oxidative damage and elevates
fertilization and pregnancy rates.

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