pineal gland pineal gland 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, which gives it its name. 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. it is one of the neuroendocrine secretory circumventricular organs in which capillaries are mostly permeable to solutes in the blood. pineal glandpineal gland or epiphysis (in red)diagram of pituitary and pineal glands in the human braindetailsprecursorneural ectoderm, roof of diencephalonarteryposterior cerebral arteryidentifierslatinglandula pinealismeshd010870neuronames297neurolex idbirnlex_1184ta98a11.2.00.001ta23862fma62033anatomical terms of neuroanatomy the pineal gland is present in almost all vertebrates, but is absent in protochordates in which there is a simple pineal homologue. the hagfish, considered as a primitive vertebrate, has a rudimentary structure regarded as the "pineal equivalent" in the dorsal diencephalon. in some species of amphibians and reptiles, the gland is linked to a light-sensing organ, variously called the parietal eye, the pineal eye or the third eye. reconstruction of the biological evolution pattern suggests that the pineal gland was originally a kind of atrophied photoreceptor that developed into a neuroendocrine organ. ancient greeks were the first to notice the pineal gland and believed it to be a valve, a guardian for the flow of pneuma. galen in the 2nd century c.e. could not find any functional role and regarded the gland as a structural support for the brain tissue. he gave the name konario, meaning cone or pinecone, which during renaissance was translated to latin as pinealis. in the 17th century, rené descartes revived the mystical purpose and described the gland as the "principal seat of the soul". in the mid-20th century, the real biological role as a neuroendocrine organ was established. etymology 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. structure the pineal gland is a midline brain structure that is unpaired. it takes its name from its pine-cone shape. 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. 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. blood supply unlike most of the mammalian brain, the pineal gland is not isolated from the body by the blood–brain barrier system; it has profuse blood flow, second only to the kidney, 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. 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. microanatomy pineal gland parenchyma with calcifications micrograph of a normal pineal gland – very high magnification micrograph of a normal pineal gland – intermediate magnification the pineal body in humans consists 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. cell typedescription pinealocytesthe 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 cellsinterstitial cells are located between the pinealocytes. they have elongated nuclei and a cytoplasm that is stained darker than that of the pinealocytes. perivascular phagocytemany capillaries are present in the gland, and perivascular phagocytes are located close to these blood vessels. the perivascular phagocytes are antigen presenting cells. pineal neuronsin 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. development the human pineal gland grows in size until about 1–2 years of age, remaining stable thereafter, although its weight increases gradually from puberty onwards. 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. symmetry 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. function one 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. 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. 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. 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. the pineal gland contains receptors for the regulatory neuropeptide, endothelin-1, which, when injected in picomolar quantities into the lateral cerebral ventricle, causes a calcium-mediated increase in pineal glucose metabolism. 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. clinical significance calcification calcification of the pineal gland is typical in young adults, and has been observed in children as young as two years of age. the internal secretions of the pineal gland are known to 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. pineal gland calcification is detrimental to its ability to synthesize melatonin and scientific literature presents inconclusive findings on whether it causes sleep problems. the calcified gland is often seen in skull x-rays. 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. calcification of the pineal gland is associated with corpora arenacea, also known as "brain sand". tumors 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. 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. 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. the clinical course of patients with pineocytomas is prolonged, averaging up to several years. 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. other animals 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. a few more complex vertebrates have lost pineal glands over the course of their evolution. the lamprey (another primitive vertebrate), however, does possess one. the lancelet branchiostoma lanceolatum, an early chordate which is a close relative to vertebrates, also lacks a recognizable pineal gland. protochordates in general do not have the distinct structure as an organ, but they have a mass of photoreceptor cells called lamellar body, which is regarded as a pineal homologue. 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 is 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. 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. in many lower vertebrates (such as species of fish, amphibians and lizards), the pineal gland is associated with parietal or pineal eye. in these animals, the parietal eye acts as a photoreceptor, and hence are also known as the third eye, and they can be seen on top of the head in some species. some extinct devonian fishes have two parietal foramina in their skulls, 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. during embryonic development, the parietal eye and the pineal organ of modern lizards and tuataras 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. the pineal organs of mammals fall into one of three categories based on shape. rodents have more structurally complex pineal glands than other mammals. crocodilians and some tropical lineages of mammals (some xenarthrans (sloths), pangolins, sirenians (manatees and dugongs), and some marsupials (sugar gliders)) have lost both their parietal eye and their pineal organ. polar mammals, such as walruses and some seals, possess unusually large pineal glands. 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. 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. pineal cytostructure seems to have evolutionary similarities to the retinal cells of the lateral eyes. 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. 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. in most vertebrates, exposure to light sets off a chain reaction of enzymatic events within