Pineal gland

Last updated

Pineal gland
Illu pituitary pineal glands.jpg
Diagram of pituitary and pineal glands in the human brain
Precursor Neural ectoderm, roof of diencephalon
Artery Posterior cerebral artery
Latin Glandula pinealis
MeSH D010870
NeuroNames 297
NeuroLex ID birnlex_1184
TA98 A11.2.00.001
TA2 3862
FMA 62033
Anatomical terms of neuroanatomy
Pineal gland or epiphysis (in red in back of the brain). Expand the image to an animated version Pineal gland.gif
Pineal gland or epiphysis (in red in back of the brain). Expand the image to an animated version

The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep patterns in both circadian and seasonal cycles. The shape of the gland resembles a pine cone from which it derived its name. [1] The pineal gland is located in the epithalamus, near the center of the brain, between the two hemispheres, tucked in a groove where the two halves of the thalamus join. [2] [3] The pineal gland is one of the neuroendocrine secretory circumventricular organs in which capillaries are mostly permeable to solutes in the blood. [4]


Nearly all vertebrate species possess a pineal gland. The most important exception is a primitive vertebrate, the hagfish. Even in the hagfish, however, there may be a "pineal equivalent" structure in the dorsal diencephalon. [5] The lancelet Branchiostoma lanceolatum , the nearest existing relative to vertebrates, also lacks a recognizable pineal gland. [6] The lamprey (another primitive vertebrate), however, does possess one. [6] A few more developed vertebrates have lost pineal glands over the course of their evolution. [7]

The results of various scientific research in evolutionary biology, comparative neuroanatomy and neurophysiology have explained the evolutionary history (phylogeny) of the pineal gland in different vertebrate species. From the point of view of biological evolution, the pineal gland represents a kind of atrophied photoreceptor. In the epithalamus of some species of amphibians and reptiles, it is linked to a light-sensing organ, known as the parietal eye, which is also called the pineal eye or third eye. [8]

René Descartes believed the human pineal gland to be the "principal seat of the soul". Academic philosophy among his contemporaries considered the pineal gland as a neuroanatomical structure without special metaphysical qualities; science studied it as one endocrine gland among many. [9]


The word pineal, from Latin pinea (pine-cone), was first used in the late 17th century to refer to the cone shape of the brain gland. [1]


The pineal gland is a midline brain structure that is unpaired. It takes its name from its pine-cone shape. [1] [10] The gland is reddish-gray and about the size of a grain of rice (5–8 mm) in humans. The pineal gland, also called the pineal body, is part of the epithalamus, and lies between the laterally positioned thalamic bodies and behind the habenular commissure. It is located in the quadrigeminal cistern near to the corpora quadrigemina. [11] It is also located behind the third ventricle and is bathed in cerebrospinal fluid supplied through a small pineal recess of the third ventricle which projects into the stalk of the gland. [12]

Blood supply

Unlike most of the mammalian brain, the pineal gland is not isolated from the body by the blood–brain barrier system; [13] it has profuse blood flow, second only to the kidney, [14] supplied from the choroidal branches of the posterior cerebral artery.

Nerve supply

The pineal gland receives a sympathetic innervation from the superior cervical ganglion. A parasympathetic innervation from the pterygopalatine and otic ganglia is also present. [15] Further, some nerve fibers penetrate into the pineal gland via the pineal stalk (central innervation). Also, neurons in the trigeminal ganglion innervate the gland with nerve fibers containing the neuropeptide PACAP.


Pineal gland parenchyma with calcifications. Pineal.jpg
Pineal gland parenchyma with calcifications.
Micrograph of a normal pineal gland - very high magnification. Pineal gland - very high mag.jpg
Micrograph of a normal pineal gland – very high magnification.
Micrograph of a normal pineal gland - intermediate magnification. Pineal gland - intermed mag.jpg
Micrograph of a normal pineal gland – intermediate magnification.

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. As it is quite cellular (in relation to the cortex and white matter), it may be mistaken for a neoplasm. [16]

Cell typeDescription
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. Their cytoplasm is lightly basophilic. With special stains, pinealocytes exhibit lengthy, branched cytoplasmic processes that extend to the connective septa and its blood vessels.
Interstitial cells Interstitial cells are located between the pinealocytes. They have elongated nuclei and a cytoplasm that is stained darker than that of 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 usually located in the pineal gland. However, this is not the case in rodents.
Peptidergic neuron-like cellsIn some species, neuronal-like peptidergic cells are present. These cells might have a paracrine regulatory function.


The human pineal gland grows in size until about 1–2 years of age, remaining stable thereafter, [17] [18] although its weight increases gradually from puberty onwards. [19] [20] The abundant melatonin levels in children are believed to inhibit sexual development, and pineal tumors have been linked with precocious puberty. When puberty arrives, melatonin production is reduced. [21]


In the zebrafish the pineal gland does not straddle the midline, but shows a left-sided bias. In humans, functional cerebral dominance is accompanied by subtle anatomical asymmetry. [22] [23] [24]


The primary function of the pineal gland is to produce melatonin. Melatonin has various functions in the central nervous system, the most important of which is to help modulate sleep patterns. Melatonin production is stimulated by darkness and inhibited by light. [25] [26] Light sensitive nerve cells in the retina detect light and send this signal to the suprachiasmatic nucleus (SCN), synchronizing the SCN to the day-night cycle. Nerve fibers then relay the daylight information from the SCN to the paraventricular nuclei (PVN), then to the spinal cord and via the sympathetic system to superior cervical ganglia (SCG), and from there into the pineal gland.

The compound pinoline is also claimed to be produced in the pineal gland; it is one of the beta-carbolines. [27] This claim is subject to some controversy.

Regulation of the pituitary gland

Studies on rodents suggest that the pineal gland influences the pituitary gland's secretion of the sex hormones, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Pinealectomy performed on rodents produced no change in pituitary weight, but caused an increase in the concentration of FSH and LH within the gland. [28] Administration of melatonin did not return the concentrations of FSH to normal levels, suggesting that the pineal gland influences pituitary gland secretion of FSH and LH through an undescribed transmitting molecule. [28]

The pineal gland contains receptors for the regulatory neuropeptide, endothelin-1, [29] which, when injected in picomolar quantities into the lateral cerebral ventricle, causes a calcium-mediated increase in pineal glucose metabolism. [30]

Regulation of bone metabolism

Studies in mice suggest that the pineal-derived melatonin regulates new bone deposition. Pineal-derived melatonin mediates its action on the bone cells through MT2 receptors. This pathway could be a potential new target for osteoporosis treatment as the study shows the curative effect of oral melatonin treatment in a postmenopausal osteoporosis mouse model. [31]

Clinical significance


Calcification of the pineal gland is typical in young adults, and has been observed in children as young as two years of age. [32] The internal secretions of the pineal gland inhibit the development of the reproductive glands because when it is severely damaged in children, development of the sexual organs and the skeleton are accelerated. [33] Pineal gland calcification is detrimental to its ability to synthesize melatonin [34] [35] but has not been shown to cause sleep problems. [36]

The calcified gland is often seen in skull x-rays. [32] Calcification rates vary widely by country and correlate with an increase in age, with calcification occurring in an estimated 40% of Americans by age seventeen. [32] Calcification of the pineal gland is associated with corpora arenacea, also known as "brain sand".


Tumors of the pineal gland are called pinealomas. These tumors are rare and 50% to 70% are germinomas that arise from sequestered embryonic germ cells. Histologically they are similar to testicular seminomas and ovarian dysgerminomas. [37]

A pineal tumor can compress the superior colliculi and pretectal area of the dorsal midbrain, producing Parinaud's syndrome. Pineal tumors also can cause compression of the cerebral aqueduct, resulting in a noncommunicating hydrocephalus. Other manifestations are the consequence of their pressure effects and consist of visual disturbances, headache, mental deterioration, and sometimes dementia-like behaviour. [38]

These neoplasms are divided into three categories: pineoblastomas, pineocytomas, and mixed tumors, based on their level of differentiation, which, in turn, correlates with their neoplastic aggressiveness. [39] The clinical course of patients with pineocytomas is prolonged, averaging up to several years. [40] The position of these tumors makes them difficult to remove surgically.

Other conditions

The morphology of the pineal gland differs markedly in different pathological conditions. For instance, it is known that its volume is reduced both in obese patients as well as patients with primary insomnia. [41]

Other animals

Most living vertebrates have pineal glands. It is likely that the common ancestor of all vertebrates had a pair of photosensory organs on the top of its head, similar to the arrangement in modern lampreys. [42] Some extinct Devonian fishes have two parietal foramina in their skulls, [43] [44] suggesting an ancestral bilaterality of parietal eyes. The parietal eye and the pineal gland of living tetrapods are probably the descendants of the left and right parts of this organ, respectively. [45]

During embryonic development, the parietal eye and the pineal organ of modern lizards [46] and tuataras [47] form together from a pocket formed in the brain ectoderm. The loss of parietal eyes in many living tetrapods is supported by developmental formation of a paired structure that subsequently fuses into a single pineal gland in developing embryos of turtles, snakes, birds, and mammals. [48]

The pineal organs of mammals fall into one of three categories based on shape. Rodents have more structurally complex pineal glands than other mammals. [49]

Crocodilians and some tropical lineages of mammals (some xenarthrans (sloths), pangolins, sirenians (manatees & dugongs), and some marsupials (sugar gliders) have lost both their parietal eye and their pineal organ. [50] [51] [49] Polar mammals, such as walruses and some seals, possess unusually large pineal glands. [50]

All amphibians have a pineal organ, but some frogs and toads also have what is called a "frontal organ", which is essentially a parietal eye. [52]

Pinealocytes in many non-mammalian vertebrates have a strong resemblance to the photoreceptor cells of the eye. Evidence from morphology and developmental biology suggests that pineal cells possess a common evolutionary ancestor with retinal cells. [53]

Pineal cytostructure seems to have evolutionary similarities to the retinal cells of the lateral eyes. [53] Modern birds and reptiles express the phototransducing pigment melanopsin in the pineal gland. Avian pineal glands are thought to act like the suprachiasmatic nucleus in mammals. [54] The structure of the pineal eye in modern lizards and tuatara is analogous to the cornea, lens, and retina of the lateral eyes of vertebrates. [48]

In most vertebrates, exposure to light sets off a chain reaction of enzymatic events within the pineal gland that regulates circadian rhythms. [55] 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 gland.

The fossilized skulls of many extinct vertebrates have a pineal foramen (opening), which in some cases is larger than that of any living vertebrate. [56] Although fossils seldom preserve deep-brain soft anatomy, the brain of the Russian fossil bird Cerebavis cenomanica from Melovatka, about 90 million years old, shows a relatively large parietal eye and pineal gland. [57]

Society and culture

Diagram of the operation of the pineal gland for Descartes in the Treatise of Man (figure published in the edition of 1664) Descartes mind and body.gif
Diagram of the operation of the pineal gland for Descartes in the Treatise of Man (figure published in the edition of 1664)

Seventeenth-century philosopher and scientist René Descartes was highly interested in anatomy and physiology. He discussed the pineal gland both in his first book, the Treatise of Man (written before 1637, but only published posthumously 1662/1664), and in his last book, The Passions of the Soul (1649) and he regarded it as "the principal seat of the soul and the place in which all our thoughts are formed." [58] In the Treatise of Man, Descartes described conceptual models of man, namely creatures created by God, which consist of two ingredients, a body and a soul. [58] [59] In the Passions, Descartes split man up into a body and a soul and emphasized that the soul is joined to the whole body by "a certain very small gland situated in the middle of the brain's substance and suspended above the passage through which the spirits in the brain's anterior cavities communicate with those in its posterior cavities". Descartes attached significance to the gland because he believed it to be the only section of the brain to exist as a single part rather than one-half of a pair. Most of Descartes's basic anatomical and physiological assumptions were totally mistaken, not only by modern standards, but also in light of what was already known in his time. [58] [60]

The notion of a "pineal-eye" is central to the philosophy of the French writer Georges Bataille, which is analyzed at length by literary scholar Denis Hollier in his study Against Architecture. In this work Hollier discusses how Bataille uses the concept of a "pineal-eye" as a reference to a blind-spot in Western rationality, and an organ of excess and delirium. [61] This conceptual device is explicit in his surrealist texts, The Jesuve and The Pineal Eye. [62]

In the late 19th century Madame Blavatsky (who founded theosophy) identified the pineal gland with the Hindu concept of the third eye, or the Ajna chakra. This association is still popular today. [58]

Rick Strassman, an author and Clinical Associate Professor of Psychiatry at the University of New Mexico School of Medicine, has theorised that the human pineal gland is capable of producing the hallucinogen N,N-Dimethyltryptamine (DMT) under certain circumstances. [63] In 2013 he and other researchers first reported DMT in the pineal gland microdialysate of rodents. [64]

In the short story "From Beyond" by H. P. Lovecraft, a scientist creates an electronic device that emits a resonance wave, which stimulates an affected person's pineal gland, thereby allowing her or him to perceive planes of existence outside the scope of accepted reality, a translucent, alien environment that overlaps our own recognized reality. It was adapted as a film of the same name in 1986. The 2013 horror film Banshee Chapter is heavily influenced by this short story.


The secretory activity of the pineal gland is only partially understood. Its location deep in the brain suggested to philosophers throughout history that it possesses particular importance. This combination led to its being regarded as a "mystery" gland with mystical, metaphysical, and occult theories surrounding its perceived functions.

The pineal gland was originally believed to be a "vestigial remnant" of a larger organ. In 1917, it was known that extract of cow pineals lightened frog skin. Dermatology professor Aaron B. Lerner and colleagues at Yale University, hoping that a substance from the pineal might be useful in treating skin diseases, isolated and named the hormone melatonin in 1958. [65] The substance did not prove to be helpful as intended, but its discovery helped solve several mysteries such as why removing the rat's pineal accelerated ovary growth, why keeping rats in constant light decreased the weight of their pineals, and why pinealectomy and constant light affect ovary growth to an equal extent; this knowledge gave a boost to the then new field of chronobiology. [66]

Additional images

The pineal body is labeled in these images.

See also

Related Research Articles

Circadian rhythm natural internal process that regulates the sleep-wake cycle

A circadian rhythm is a natural, internal process that regulates the sleep-wake cycle and repeats on each rotation of the Earth roughly every 24 hours. It can refer to any biological process that displays an endogenous, entrainable oscillation of about 24 hours. These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in plants, animals, fungi, and cyanobacteria.

Blood–brain barrier Semipermeable capillary border that allows selective passage of blood constituents into the brain

The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside. The blood-brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some molecules by passive diffusion, as well as the selective transport of various nutrients, ions, organic anions, and macromolecules such as glucose, water and amino acids that are crucial to neural function.


Melatonin is a hormone primarily released by the pineal gland that regulates the sleep–wake cycle. As a dietary supplement, it is often used for the short-term treatment of insomnia, such as from jet lag or shift work, and is typically taken by mouth. Evidence of its benefit for this use, however, is not strong. A 2017 review found that sleep onset occurred six minutes faster with use, but found no change in total time asleep. The melatonin receptor agonist medication ramelteon may work as well as melatonin supplements.

Anterior pituitary Anterior lobe of the pituitary gland

A major organ of the endocrine system, the anterior pituitary is the glandular, anterior lobe that together with the posterior lobe makes up the pituitary gland (hypophysis). The anterior pituitary regulates several physiological processes, including stress, growth, reproduction, and lactation. Proper functioning of the anterior pituitary and of the organs it regulates can often be ascertained via blood tests that measure hormone levels.

Suprachiasmatic nucleus Part of the brains hypothalamus

The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle. The mouse SCN contains approximately 20,000 neurons.


Pinealocytes are the main cells contained in the pineal gland, located behind the third ventricle and between the two hemispheres of the brain. The primary function of the pinealocytes is the secretion of the hormone melatonin, important in the regulation of circadian rhythms. In humans, the suprachiasmatic nucleus of the hypothalamus communicates the message of darkness to the pinealocytes, and as a result, controls the day and night cycle. It has been suggested that pinealocytes are derived from photoreceptor cells. Research has also shown the decline in the number of pinealocytes by way of apoptosis as the age of the organism increases. There are two different types of pinealocytes, type I and type II, which have been classified based on certain properties including shape, presence or absence of infolding of the nuclear envelope, and composition of the cytoplasm.


Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.


The epithalamus is a (dorsal) posterior segment of the diencephalon. The diencephalon is a part of the forebrain that also contains the thalamus, the hypothalamus and pituitary gland. The epithalamus includes the habenular nuclei and their interconnecting fibers, the habenular commissure, the stria medullaris and the pineal gland.

Corpora arenacea are calcified structures in the pineal gland and other areas of the brain such as the choroid plexus. Older organisms have numerous corpora arenacea, whose function, if any, is unknown. Concentrations of "brain sand" increase with age, so the pineal gland becomes increasingly visible on X-rays over time, usually by the third or fourth decade. They are sometimes used as anatomical landmarks in radiological examinations.

Pinealoma endocrine gland located in the pineal gland located in the brain

A pinealoma is a tumor of the pineal gland, a part of the brain that produces melatonin. If a pinealoma destroys the cells of the pineal gland in a child, it can cause precocious puberty.

Circumventricular organs Interfaces between the brain and the circulatory system

Circumventricular organs (CVOs) are structures in the brain characterized by their extensive and highly permeable capillaries, unlike those in the rest of the brain where there exists a blood–brain barrier (BBB) at the capillary level. Although the term "circumventricular organs" was originally proposed in 1958 by Austrian anatomist Helmut O. Hofer concerning structures around the brain ventricular system, the penetration of blood-borne dyes into small specific CVO regions was discovered in the early 20th century. The permeable CVOs enabling rapid neurohumoral exchange include the subfornical organ (SFO), the area postrema (AP), the vascular organ of lamina terminalis (VOLT), the median eminence, the pituitary neural lobe, and the pineal gland.

Parietal eye photoreceptive part of the epithalamus present in some animal species

A parietal eye, also known as a third eye or pineal eye, is a part of the epithalamus present in some species of fish, amphibians and reptiles. The eye is located at the top of the head, is photoreceptive and is associated with the pineal gland, regulating circadian rhythmicity and hormone production for thermoregulation.

Melatonin receptors are G protein-coupled receptors (GPCR) which bind melatonin. Three types of melatonin receptors have been cloned. The MT1 (or Mel1A or MTNR1A) and MT2 (or Mel1B or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype MT3 (or Mel1C or MTNR1C) has been identified in amphibia and birds. The receptors are crucial in the signal cascade of melatonin. In the field of chronobiology, melatonin has been found to be a key player in the synchrony of biological clocks. Melatonin secretion by the pineal gland has circadian rhythmicity regulated by the suprachiasmatic nucleus (SCN) found in the brain. The SCN functions as the timing regulator for melatonin; melatonin then follows a feedback loop to decrease SCN neuronal firing. The receptors MT1 and MT2 control this process. Melatonin receptors are found throughout the body in places such as the brain, the retina of the eye, the cardiovascular system, the liver and gallbladder, the colon, the skin, the kidneys, and many others. In 2019, crystal structures of MT1 and MT2 were reported.

Aralkylamine <i>N</i>-acetyltransferase

Aralkylamine N-acetyltransferase (AANAT), also known as arylalkylamine N-acetyltransferase or serotonin N-acetyltransferase (SNAT), is an enzyme that is involved in the day/night rhythmic production of melatonin, by modification of serotonin. It is in humans encoded by the ~2.5 kb AANAT gene containing four exons, located on chromosome 17q25. The gene is translated into a 23 kDa large enzyme. It is well conserved through evolution and the human form of the protein is 80% identical to sheep and rat AANAT. It is an acetyl-CoA-dependent enzyme of the GCN5-related family of N-acetyltransferases (GNATs). It may contribute to multifactorial genetic diseases such as altered behavior in sleep/wake cycle and research is on-going with the aim of developing drugs that regulate AANAT function.

Acetylserotonin O-methyltransferase mammalian protein found in Homo sapiens

N-Acetylserotonin O-methyltransferase, also known as ASMT, is an enzyme which catalyzes the final reaction in melatonin biosynthesis: converting Normelatonin to melatonin. This reaction is embedded in the more general tryptophan metabolism pathway. The enzyme also catalyzes a second reaction in tryptophan metabolism: the conversion of 5-hydroxy-indoleacetate to 5-methoxy-indoleacetate. The other enzyme which catalyzes this reaction is n-acetylserotonin-o-methyltransferase-like-protein.

Melatonin receptor 1A protein-coding gene in the species Homo sapiens

Melatonin receptor type 1A is a protein that in humans is encoded by the MTNR1A gene.

Light effects on circadian rhythm are the effects that light has on circadian rhythm.

Melatonin receptor 1B protein-coding gene in the species Homo sapiens

Melatonin receptor 1B, also known as MTNR1B, is a protein that in humans is encoded by the MTNR1B gene.

A chronobiotic is an agent that can cause phase adjustment of the body clock. That is, it is a substance capable of therapeutically entraining or re-entraining long-term desynchronized or short-term dissociated circadian rhythms in mammals, or prophylactically preventing their disruption following an environmental insult such as is caused by rapid travel across several time zones. The most widely recognized chronobiotic is the hormone melatonin, secreted at night in both diurnal and nocturnal species.

Brain-specific Homeobox is a protein that in humans is encoded by the BSX gene.


  1. 1 2 3 "Pineal (as an adjective)". Online Etymology Dictionary, Douglas Harper. 2018. Retrieved 27 October 2018.
  2. Macchi MM, Bruce JN (2004). "Human pineal physiology and functional significance of melatonin". Frontiers in Neuroendocrinology. 25 (3–4): 177–95. doi:10.1016/j.yfrne.2004.08.001. PMID   15589268. S2CID   26142713.
  3. Arendt J, Skene DJ (February 2005). "Melatonin as a chronobiotic". Sleep Medicine Reviews. 9 (1): 25–39. doi:10.1016/j.smrv.2004.05.002. PMID   15649736. Exogenous melatonin has acute sleepiness-inducing and temperature-lowering effects during 'biological daytime', and when suitably timed (it is most effective around dusk and dawn) it will shift the phase of the human circadian clock (sleep, endogenous melatonin, cortisol) to earlier (advance phase shift) or later (delay phase shift) times.
  4. Gross PM, Weindl A (December 1987). "Peering through the windows of the brain". Journal of Cerebral Blood Flow and Metabolism. 7 (6): 663–72. doi:10.1038/jcbfm.1987.120. PMID   2891718. S2CID   18748366.
  5. Ooka-Souda S, Kadota T, Kabasawa H (December 1993). "The preoptic nucleus: the probable location of the circadian pacemaker of the hagfish, Eptatretus burgeri". Neuroscience Letters. 164 (1–2): 33–6. doi:10.1016/0304-3940(93)90850-K. PMID   8152610. S2CID   40006945.
  6. 1 2 Vernadakis AJ, Bemis WE, Bittman EL (April 1998). "Localization and partial characterization of melatonin receptors in amphioxus, hagfish, lamprey, and skate". General and Comparative Endocrinology. 110 (1): 67–78. doi:10.1006/gcen.1997.7042. PMID   9514841.
  7. Erlich SS, Apuzzo ML (September 1985). "The pineal gland: anatomy, physiology, and clinical significance". Journal of Neurosurgery. 63 (3): 321–41. doi:10.3171/jns.1985.63.3.0321. PMID   2862230. S2CID   29929205.
  8. Eakin, Richard M. (1973). The Third Eye. Berkeley: University of California Press.
  9. Lokhorst, Gert-Jan (2018), "Descartes and the Pineal Gland", in Zalta, Edward N. (ed.), The Stanford Encyclopedia of Philosophy (Winter 2018 ed.), Metaphysics Research Lab, Stanford University, retrieved 17 December 2019
  10. Bowen R. "The Pineal Gland and Melatonin". Archived from the original on 24 November 2011. Retrieved 14 October 2011.
  11. Chen CY, Chen FH, Lee CC, Lee KW, Hsiao HS (October 1998). "Sonographic characteristics of the cavum velum interpositum" (PDF). AJNR. American Journal of Neuroradiology. 19 (9): 1631–5. PMID   9802483.
  12. Dorland's. Illustrated Medical Dictionary. Elsevier Saunders. p. 1607. ISBN   978-1-4160-6257-8.
  13. Pritchard TC, Alloway KD (1999). Medical Neuroscience (Google books preview). Hayes Barton Press. pp. 76–77. ISBN   978-1-889325-29-3 . Retrieved 8 February 2009.
  14. Arendt J: Melatonin and the Mammalian Pineal Gland, ed 1. London. Chapman & Hall, 1995, p 17
  15. Møller M, Baeres FM (July 2002). "The anatomy and innervation of the mammalian pineal gland". Cell and Tissue Research. 309 (1): 139–50. doi:10.1007/s00441-002-0580-5. PMID   12111544. S2CID   25719864.
  16. Kleinschmidt-DeMasters BK, Prayson RA (November 2006). "An algorithmic approach to the brain biopsy--part I". Archives of Pathology & Laboratory Medicine. 130 (11): 1630–8. doi:10.1043/1543-2165(2006)130[1630:AAATTB]2.0.CO;2 (inactive 19 October 2020). PMID   17076524.CS1 maint: DOI inactive as of October 2020 (link)
  17. Schmidt F, Penka B, Trauner M, Reinsperger L, Ranner G, Ebner F, Waldhauser F (April 1995). "Lack of pineal growth during childhood". The Journal of Clinical Endocrinology and Metabolism. 80 (4): 1221–5. doi:10.1210/jcem.80.4.7536203. PMID   7536203.
  18. Sumida M, Barkovich AJ, Newton TH (February 1996). "Development of the pineal gland: measurement with MR". AJNR. American Journal of Neuroradiology. 17 (2): 233–6. PMID   8938291.
  19. Tapp E, Huxley M (September 1971). "The weight and degree of calcification of the pineal gland". The Journal of Pathology. 105 (1): 31–9. doi:10.1002/path.1711050105. PMID   4943068. S2CID   38346296.
  20. Tapp E, Huxley M (October 1972). "The histological appearance of the human pineal gland from puberty to old age". The Journal of Pathology. 108 (2): 137–44. doi:10.1002/path.1711080207. PMID   4647506. S2CID   28529644.
  21. "Melatonin Production and Age". Chronobiology. Medichron Publications.
  22. Snelson CD, Santhakumar K, Halpern ME, Gamse JT (May 2008). "Tbx2b is required for the development of the parapineal organ". Development. 135 (9): 1693–702. doi:10.1242/dev.016576. PMC   2810831 . PMID   18385257.
  23. Snelson CD, Burkart JT, Gamse JT (December 2008). "Formation of the asymmetric pineal complex in zebrafish requires two independently acting transcription factors". Developmental Dynamics. 237 (12): 3538–44. doi:10.1002/dvdy.21607. PMC   2810829 . PMID   18629869.
  24. Snelson CD, Gamse JT (June 2009). "Building an asymmetric brain: development of the zebrafish epithalamus". Seminars in Cell & Developmental Biology. 20 (4): 491–7. doi:10.1016/j.semcdb.2008.11.008. PMC   2729063 . PMID   19084075.
  25. Axelrod J (September 1970). "The pineal gland". Endeavour. 29 (108): 144–8. PMID   4195878.
  26. Lowrey PL, Takahashi JS (2000). "Genetics of the mammalian circadian system: Photic entrainment, circadian pacemaker mechanisms, and posttranslational regulation". Annual Review of Genetics. 34 (1): 533–562. doi:10.1146/annurev.genet.34.1.533. PMID   11092838.
  27. Callaway JC, Gyntber J, Poso A, Airaksinen MM, Vepsäläinen J (1994). "The pictet-spengler reaction and biogenic tryptamines: Formation of tetrahydro-β-carbolines at physiologicalpH". Journal of Heterocyclic Chemistry. 31 (2): 431–435. doi:10.1002/jhet.5570310231.
  28. 1 2 Motta M, Fraschini F, Martini L (November 1967). "Endocrine effects of pineal gland and of melatonin". Proceedings of the Society for Experimental Biology and Medicine. 126 (2): 431–5. doi:10.3181/00379727-126-32468. PMID   6079917. S2CID   28964258.
  29. Naidoo V, Naidoo S, Mahabeer R, Raidoo DM (May 2004). "Cellular distribution of the endothelin system in the human brain". Journal of Chemical Neuroanatomy. 27 (2): 87–98. doi:10.1016/j.jchemneu.2003.12.002. PMID   15121213. S2CID   39053816.
  30. Gross PM, Wainman DS, Chew BH, Espinosa FJ, Weaver DF (March 1993). "Calcium-mediated metabolic stimulation of neuroendocrine structures by intraventricular endothelin-1 in conscious rats". Brain Research. 606 (1): 135–42. doi:10.1016/0006-8993(93)91581-C. PMID   8461995. S2CID   12713010.
  31. Sharan K, Lewis K, Furukawa T, Yadav VK (September 2017). "Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway". Journal of Pineal Research. 63 (2): e12423. doi:10.1111/jpi.12423. PMC   5575491 . PMID   28512916.
  32. 1 2 3 Zimmerman RA (1982). "Age-Related Incidence of Pineal Calcification Detected by Computed Tomography" (PDF). Radiology. Radiological Society of North America. 142 (3): 659–62. doi:10.1148/radiology.142.3.7063680. PMID   7063680. Archived from the original (PDF) on 24 March 2012. Retrieved 21 June 2012.
  33. "The Pineal Body". Human Anatomy (Gray's Anatomy). Archived from the original on 26 August 2011. Retrieved 7 September 2011.
  34. Kunz, D.; Schmitz, S.; Mahlberg, R.; Mohr, A.; Stöter, C.; Wolf, K. J.; Herrmann, W. M. (21 December 1999). "A new concept for melatonin deficit: on pineal calcification and melatonin excretion". Neuropsychopharmacology. 21 (6): 765–772. doi:10.1016/S0893-133X(99)00069-X. ISSN   0893-133X. PMID   10633482. S2CID   20184373.
  35. Tan, Dun Xian; Xu, Bing; Zhou, Xinjia; Reiter, Russel J. (31 January 2018). "Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland". Molecules. 23 (2): 301. doi:10.3390/molecules23020301. ISSN   1420-3049. PMC   6017004 . PMID   29385085.
  36. Del Brutto, Oscar H.; Mera, Robertino M.; Lama, Julio; Zambrano, Mauricio; Castillo, Pablo R. (November 2014). "Pineal gland calcification is not associated with sleep-related symptoms. A population-based study in community-dwelling elders living in Atahualpa (rural coastal Ecuador)". Sleep Medicine. 15 (11): 1426–1427. doi:10.1016/j.sleep.2014.07.008. ISSN   1878-5506. PMID   25277665.
  37. Kumar V, Abbas AK, Aster JC (5 September 2014). Robbins & Cotran Pathologic Basis of Disease. p. 1137. ISBN   9780323296359.
  38. Bruce J. "Pineal Tumours". eMedicine. Archived from the original on 5 September 2015. Retrieved 25 September 2015.
  39. "Pineal Tumours". American Brain Tumour Association. Archived from the original on 26 September 2015. Retrieved 25 September 2015.
  40. Clark AJ, Sughrue ME, Ivan ME, Aranda D, Rutkowski MJ, Kane AJ, Chang S, Parsa AT (November 2010). "Factors influencing overall survival rates for patients with pineocytoma". Journal of Neuro-Oncology. 100 (2): 255–60. doi:10.1007/s11060-010-0189-6. PMC   2995321 . PMID   20461445.
  41. Tan, Dun Xian; Xu, Bing; Zhou, Xinjia; Reiter, Russel J. (February 2018). "Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland". Molecules. 23 (2): 301. doi:10.3390/molecules23020301. PMID   29385085. S2CID   25611663.
  42. Cole WC, Youson JH (October 1982). "Morphology of the pineal complex of the anadromous sea lamprey, Petromyzon marinus L". The American Journal of Anatomy. 165 (2): 131–63. doi:10.1002/aja.1001650205. PMID   7148728.
  43. Cope ED (1888). "The pineal eye in extinct vertebrates". American Naturalist. 22 (262): 914–917. doi:10.1086/274797. S2CID   85280810.
  44. Schultze H (1993). "Patterns of diversity in the skulls of jawed fishes". In Hanken J, Hall BK (eds.). The Skull. 2: Patterns of Structural and Systematic Diversity. Chicago, Illinois: University of Chicago Press. pp. 189–254. ISBN   9780226315683 . Retrieved 2 February 2017.
  45. Dodt E (1973). "The parietal eye (pineal and parietal organs) of lower vertebrates". Visual Centers in the Brain. Springer. pp. 113–140.
  46. Tosini G (1997). "The pineal complex of reptiles: physiological and behavioral roles". Ethology Ecology & Evolution. 9 (4): 313–333. doi:10.1080/08927014.1997.9522875.
  47. Dendy A (1911). "On the structure, development and morphological interpretation of the pineal organs and adjacent parts of the brain in the tuatara (Sphenodon punctatus)". Philosophical Transactions of the Royal Society of London B. 201 (274–281): 227–331. doi:10.1098/rstb.1911.0006.
  48. 1 2 Quay WB (1979). "The parietal eye–pineal complex". In Gans C, Northcutt RG, Ulinski P (eds.). Biology of the Reptilia. Volume 9. Neurology A. London: Academic Press. pp. 245–406. Archived from the original on 3 February 2017.
  49. 1 2 Vollrath L (1979). Comparative morphology of the vertebrate pineal complex. Progress in Brain Research. 52. pp. 25–38. doi:10.1016/S0079-6123(08)62909-X. ISBN   9780444801142. PMID   398532.
  50. 1 2 Ralph CL (December 1975). "The pineal gland and geographical distribution of animals". International Journal of Biometeorology. 19 (4): 289–303. Bibcode:1975IJBm...19..289R. doi:10.1007/bf01451040. PMID   1232070. S2CID   30406445.
  51. Ralph C, Young S, Gettinger R, O'Shea TJ (1985). "Does the manatee have a pineal body?". Acta Zoologica. 66: 55–60. doi:10.1111/j.1463-6395.1985.tb00647.x.
  52. Adler K (1976). "Extraocular photoreception in amphibians". Photochemistry and Photobiology. 23 (4): 275–298. doi:10.1111/j.1751-1097.1976.tb07250.x. PMID   775500. S2CID   33692776.
  53. 1 2 Klein DC (August 2004). "The 2004 Aschoff/Pittendrigh lecture: Theory of the origin of the pineal gland--a tale of conflict and resolution". Journal of Biological Rhythms. 19 (4): 264–79. doi:10.1177/0748730404267340. PMID   15245646. S2CID   17834354.
  54. Natesan A, Geetha L, Zatz M (July 2002). "Rhythm and soul in the avian pineal". Cell and Tissue Research. 309 (1): 35–45. doi:10.1007/s00441-002-0571-6. PMID   12111535. S2CID   26023207.
  55. Moore RY, Heller A, Wurtman RJ, Axelrod J (January 1967). "Visual pathway mediating pineal response to environmental light". Science. 155 (3759): 220–3. Bibcode:1967Sci...155..220M. doi:10.1126/science.155.3759.220. PMID   6015532. S2CID   44377291.
  56. Edinger T (1955). "The size of parietal foramen and organ in reptiles: a rectification". Bulletin of the Museum of Comparative Zoology. 114: 1–34. Archived from the original on 1 December 2017.
  57. Kurochkin EN, Dyke GJ, Saveliev SV, Pervushov EM, Popov EV (June 2007). "A fossil brain from the Cretaceous of European Russia and avian sensory evolution". Biology Letters. 3 (3): 309–13. doi:10.1098/rsbl.2006.0617. PMC   2390680 . PMID   17426009.
  58. 1 2 3 4 Lokhorst G (2015). Descartes and the Pineal Gland. Stanford: The Stanford Encyclopedia of Philosophy.
  59. Descartes R. "The Passions of the Soul" excerpted from "Philosophy of the Mind," Chalmers, D. New York: Oxford University Press, Inc.; 2002. ISBN   978-0-19-514581-6
  60. Wikisource:Ethics (Spinoza)/Part 5
  61. Hollier, D, Against Architecture: The Writings of Georges Bataille, trans. Betsy Wing, MIT, 1989.
  62. Bataille, G, Visions of Excess: Selected Writings, 1927–1939 (Theory and History of Literature, Vol 14), trans. Allan Stoekl et al., Manchester University Press, 1985
  63. Strassman R (2000). DMT: The Spirit Molecule. Inner Traditions. ISBN   978-1594779732. Archived from the original on 6 January 2017.
  64. Barker SA, Borjigin J, Lomnicka I, Strassman R (December 2013). "LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate" (PDF). Biomedical Chromatography. 27 (12): 1690–700. doi:10.1002/bmc.2981. hdl:2027.42/101767. PMID   23881860.
  65. Lerner AB, Case JD, Takahashi Y (July 1960). "Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands". The Journal of Biological Chemistry. 235: 1992–7. PMID   14415935.
  66. Coates PM, Blackman MR, Cragg GM, Levine M, Moss J, White JD (2005). Encyclopedia of Dietary Supplements. CRC Press. p. 457. ISBN   978-0-8247-5504-1 . Retrieved 31 March 2009.