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Pineal gland
Illu endocrine system.jpg
Endocrine system
Latin glandula pinealis
Gray's subject #276 1277
MeSH [1]
Illu pituitary pineal glands.jpg
Diagram of pituitary and pineal glands.

The pineal gland (also called the pineal body, epiphysis cerebri, epiphysis or the "third eye") is a small endocrine gland in the vertebrate brain. It produces melatonin, a hormone that affects the modulation of wake/sleep patterns and photoperiodic (seasonal) functions.[1][2] It is shaped like a tiny pine cone (hence its name), and is located near to the center of the brain, between the two hemispheres, tucked in a groove where the two rounded thalamic bodies join. Unlike much of the rest of the brain, the pineal gland is not isolated from the body by the blood-brain barrier system.[3]


The pineal gland is reddish-gray and about the size of a pea (8 mm in humans), located just rostro-dorsal to the superior colliculus and behind and beneath the stria medullaris, between the laterally positioned thalamic bodies. It is part of the epithalamus.

The pineal gland is a midline structure, and is often seen in plain skull X-rays, as it is often calcified. Calcification is typically due to intake of the fluoride found in water and toothpaste.

Structure and composition

The pineal body consists in humans of a lobular parenchyma of pinealocytes surrounded by connective tissue spaces. The gland's surface is covered by a pial capsule.

The pineal gland consists mainly of pinealocytes, but four other cell types have been identified.

Cell type Description
pinealocytes The pinealocytes consist of a cell body with 4-6 processes emerging. They produce and secrete melatonin. The pinealocytes can be stained by special silver impregnation methods.
interstitial cells Interstitial cells are located between the pinealocytes.
perivascular phagocyte Many capillaries are present in the gland, and perivascular phagocytes are located close to these blood vessels. The perivascular phagocytes are antigen presenting cells.
pineal neurons In higher vertebrates neurons are located in the pineal gland. However, these are not present in rodents.
peptidergic neuron-like cells In some species, neuronal-like peptidergic cells are present. These cells might have a paracrine regulatory function.

The pineal gland receives a sympathetic innervation from the superior cervical ganglion. However, a parasympathetic innervation from the sphenopalatine and otic ganglia is also present. Further, some nerve fibers penetrate into the pineal gland via the pineal stalk (central innervation). Finally, neurons in the trigeminal ganglion innervates the gland with nerve fibers containing the neuropeptide, PACAP. Human follicles contain a variable quantity of gritty material, called corpora arenacea (or "acervuli", or "brain sand"). Chemical analysis shows that they are composed of calcium phosphate, calcium carbonate, magnesium phosphate, and ammonium phosphate.[4] Recently, calcite deposits have been described as well.[5] Calcium and phosphorus deposits in the pineal gland have been linked with aging.[6]

Miscellaneous anatomy

Pinealocytes in many non-mammalian vertebrates have a strong resemblance to the photoreceptor cells of the eye. Some evolutionary biologists believe that the vertebrate pineal cells share a common evolutionary ancestor with retinal cells.[7]

In some vertebrates, exposure of the pineal to light can directly set off a chain reaction of enzymatic events which regulate circadian rhythms.[8] Some early vertebrate fossil skulls have a pineal foramen (opening). This corroborates with the physiology of the modern "living fossils", the lamprey and the tuatara, and some other vertebrates which have a parietal organ or "third eye" which, in some of them, is photosensitive. The third eye represents evolution’s earlier approach to photoreception.[9] The structures of the third eye in the tuatara are homologous to the cornea, lens and retina, though the latter resembles that of an octopus rather than a vertebrate retina. The asymmetrical whole consists of the "eye" to the left and the pineal sac to the right. "In animals that have lost the parietal eye, including mammals, the pineal sac is retained and condensed into the form of the pineal gland."[9]

Fossils seldom preserve soft anatomy. The brain of the Russian Melovatka bird, about 90 million years old, is an exception, and it shows a larger-than-expected parietal eye and pineal gland.[10]

In humans and other mammals, the light signals necessary to set circadian rhythms are sent from the eye through the retinohypothalamic system to the suprachiasmatic nuclei (SCN) and the pineal.


The pineal gland was originally believed to be a "vestigial remnant" of a larger organ (much as the appendix was thought to be a vestigial digestive organ). Aaron Lerner and colleagues at Yale University discovered that melatonin, the most potent compound then known to lighten frog skin, was present in the highest concentrations in the pineal.[11] Melatonin is a derivative of the amino acid tryptophan, which also has other functions in the central nervous system. The production of melatonin by the pineal gland is stimulated by darkness and inhibited by light.[12] Photosensitive cells in the retina detect light and directly signal the suprachiasmatic nucleus (SCN), entraining it to the 24 hour clock. Fibers project from the SCN to the paraventricular nuclei (PVN), which relay the circadian signals to the spinal cord and out via the sympathetic system to superior cervical ganglia (SCG), and from there into the pineal gland. The function(s) of melatonin in humans is not clear; it is commonly prescribed for the treatment of circadian rhythm sleep disorders.

There is complementary evidence that the pineal gland is involved in the regulation of sleep in humans and of the full circadian rhythm in other species. It is interesting to note that in some species such as lizards the gland contains light sensitive neurons.

The human pineal gland grows in size until about 1-2 years of age, remaining stable thereafter[13] [14], although its weight increases gradually from puberty onwards [15][16]. It appears to play a major role in sexual development[citation needed], hibernation in animals[citation needed], metabolism, and seasonal breeding. The abundant melatonin levels in children is believed to inhibit sexual development, and pineal tumors have been linked with precocious puberty[citation needed]. When puberty arrives, melatonin production is reduced. Calcification of the pineal gland is typical in adults.

Diagram of pituitary and pineal glands.

Gray's FIG. 719– Hind- and mid-brains; postero-lateral view. (Pineal gland near top.)

Pineal cytostructure seems to have evolutionary similarities to the retinal cells of chordates.[17] Modern birds and reptiles have been found to express the phototransducing pigment melanopsin in the pineal gland. Avian pineal glands are believed to act like the suprachiasmatic nucleus in mammals.[18]

Studies suggest that in rodents the pineal gland may influence the actions of recreational drugs, such as cocaine,[19] and antidepressants, such as fluoxetine (Prozac),[20] and its hormone melatonin can protect against neurodegeneration.[21]

The compound pinoline is also produced in the pineal gland; it is one of the beta-carbolines. The biological activity of this molecule is of interest as a potential free radical scavenger (antioxidant), similar to that function of melatonin.[22] It also acts as an endogenous MAOI.

Cultures, philosophies and mythologies

The secretory activity of the pineal gland has only relatively recently become understood. Historically, its location close to the geographical centre in the brain suggested to philosophers that it possessed particular importance. This combination led to its being a "mystery" gland with myth, superstition and metaphysical theories surrounding its perceived function.

Galen was of the opinion that it might be responsible for the flow of thought. [23]

René Descartes, who dedicated much time to the study of the pineal gland,[24] called it the "seat of the soul".[25] He believed that it was the point of connection between the rational soul or intellect and the body.[26]

The notion of a 'pineal-eye' is central to the philosophy of the seminal French writer Georges Bataille, which is analyzed at length by literary scholar Denis Hollier in his study Against Architecture.[27] In this work Hollier discusses how Bataille uses the concept of a 'pineal-eye' as a reference to a blind-spot in Western rationality.

Additional images

See also


  1. Macchi M, Bruce J (2004). Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol 25 (3-4): 177–95.
  2. Arendt J, Skene DJ (2005). Melatonin as a chronobiotic. Sleep Med Rev 9 (1): 25–39.
  3. Pritchard, Thomas C.; Alloway, Kevin Douglas (1999). Medical Neuroscience (Google books preview), 76-77, Hayes Barton Press. URL accessed 2009-02-08.
  4. Bocchi G, Valdre G (1993). Physical, chemical, and mineralogical characterization of carbonate-hydroxyapatite concretions of the human pineal gland. J Inorg Biochem 49 (3): 209–20.
  5. Baconnier S, Lang S, Polomska M, Hilczer B, Berkovic G, Meshulam G (2002). Calcite microcrystals in the pineal gland of the human brain: first physical and chemical studies. Bioelectromagnetics 23 (7): 488–95.
  7. Klein D (2004). The 2004 Aschoff/Pittendrigh lecture: Theory of the origin of the pineal gland--a tale of conflict and resolution. J Biol Rhythms 19 (4): 264–79.
  8. Moore RY, Heller A, Wurtman RJ, Axelrod J. Visual pathway mediating pineal response to environmental light. Science 1967;155(759):220–3. PMID 6015532
  9. 9.0 9.1 Schwab, I. R., O’Connor, G. R. (March 2005). The lonely eye. British Journal of Ophthalmology 89 (3): 256.
  10. Kurochkin, Evgeny N., Gareth J. Dyke, Sergei V. Saveliev, Evgeny M. Pervushov, Evgeny V. Popov (June 2007). A fossil brain from the Cretaceous of European Russia and avian sensory evolution. Biology Letters 3 (3): 309-313.
  11. Lerner AB, Case JD, Takahashi Y (1960). Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands. J Biol Chem 235: 1992–7.
  12. Axelrod J (1970). The pineal gland. Endeavour 29 (108): 144–8.
  13. Lack of pineal growth during childhood. Schmidt F, Penka B, Trauner M, Reinsperger L, Ranner G, Ebner F, Waldhauser F. J Clin Endocrinol Metab. 1995 Apr;80(4):1221-5.
  14. Development of the pineal gland: measurement with MR. Sumida M, Barkovich AJ, Newton TH. AJNR Am J Neuroradiol. 1996 Feb;17(2):233-6.
  15. Tapp E, Huxley M. The weight and degree of calcification of the pineal gland. J Pathol 1971;105:31–39
  16. Tapp E, Huxley M. The histological appearance of the human pineal gland from puberty to old age. J Pathol 1972;108:137–144
  17. Klein D (2004). The 2004 Aschoff/Pittendrigh lecture: Theory of the origin of the pineal gland--a tale of conflict and resolution. J Biol Rhythms 19 (4): 264–79.
  18. Natesan A, Geetha L, Zatz M (2002). Rhythm and soul in the avian pineal. Cell Tissue Res 309 (1): 35–45.
  19. Uz T, Akhisaroglu M, Ahmed R, Manev H (2003). The pineal gland is critical for circadian Period1 expression in the striatum and for circadian cocaine sensitization in mice. Neuropsychopharmacology 28 (12): 2117–23.
  20. Uz T, Dimitrijevic N, Akhisaroglu M, Imbesi M, Kurtuncu M, Manev H (2004). The pineal gland and anxiogenic-like action of fluoxetine in mice. Neuroreport 15 (4): 691–4.
  21. Manev H, Uz T, Kharlamov A, Joo J (1996). Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats. FASEB J 10 (13): 1546–51.
  22. Schiller, Erich; Bartsch, H. (2003). Free Radicals and Inhalation Pathology: Respiratory System, Mononuclear Phagocyte System, Hypoxia and Reoxygenation, Pneumoconioses, and Other Granulomatoses, Cancer (Google Books, page view), 107, Springer. URL accessed 2009-02-14.
  23. *Reber, A.S & Reber, E.S. (2001). Dictionary of Psychology. London. Penguin.
  24. Descartes and the Pineal Gland (Stanford Encyclopedia of Philosophy)
  25. Descartes R. Treatise of Man. New York: Prometheus Books; 2003. ISBN 1-59102-090-5
  26. Descartes R. "The Passions of the Soul" excerpted from "Philosophy of the Mind", Chalmers, D. New York: Oxford University Press, Inc.; 2002. ISBN-13 978-0-19-514581-6
  27. Hollier, D, Against Architecture: The Writings of Georges Bataille, trans. Betsy Wing, MIT, 1989.

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