Pinealocytes are the main cells contained in the

pineal gland The pineal gland (also known as the pineal body or epiphysis cerebri) is a small endocrine gland in the brain of most vertebrates. It produces melatonin, a serotonin-derived hormone, which modulates sleep, sleep patterns following the diurnal c ...

, located behind the

third ventricle The third ventricle is one of the four connected cerebral ventricles of the ventricular system within the mammalian brain. It is a slit-like cavity formed in the diencephalon between the two thalami, in the midline between the right and lef ...

and between the two hemispheres of the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

. The primary function of the pinealocytes is the secretion of the hormone

melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...

, important in the regulation of

circadian rhythm A circadian rhythm (), or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism (i.e., Endogeny (biology), endogenous) and responds to the env ...

s. In humans, the

suprachiasmatic nucleus The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for regulating sleep cycles in animals. Reception of light inputs from photosensitive r ...

of the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

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 A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiatio ...

. Research has also shown the decline in the number of pinealocytes by way of

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

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 The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

Types of pinealocytes

Type 1 pinealocytes

Type 1 pinealocytes are also known as light pinealocytes because they stain at a low density when viewed under a

light microscope The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible spectrum, visible light and a system of lens (optics), lenses to generate magnified images of small objects. Optical microscopes ...

and appear lighter to the human eye. These Type 1 cells have been identified through research to have a round or oval shape and a diameter ranging from 7–11 micrometers. Type 1 pinealocytes are typically more numerous in both children and adults than Type 2 pinealocytes. They are also considered to be the more active cell because of the presence of certain cellular contents, including a high concentration of

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

. Another finding consistent with Type 1 pinealocytes is the increase in the amount of

lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

s and dense granules present in the cells as the age of the organism increases, possibly indicating the importance of autophagocytosis in these cells. Research has also shown that Type 1 pinealocytes contain the neurotransmitter

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

, which later is converted to

, the main

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

secreted by the

Type 2 pinealocytes

Type 2 pinealocytes are also known as dark pinealocytes because they stain at a high density when viewed under a

and appear darker to the human eye. As indicated by research and microscopy, they are round, oval, or elongated cells with a diameter of about 7–11.2 micrometers. The

nucleus Nucleus (: nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucleu ...

of a Type 2 pinealocyte contains many infoldings which contain large amounts of

rough endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for "little n ...

and

ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

s. An abundance of

cilia The cilium (: cilia; ; in Medieval Latin and in anatomy, ''cilium'') is a short hair-like membrane protrusion from many types of eukaryotic cell. (Cilia are absent in bacteria and archaea.) The cilium has the shape of a slender threadlike proj ...

and

centriole In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers ( Pinophyta), flowering plants ( angiosperms) and most fungi, an ...

s has also been found in these Type 2 cells of the

. Unique to the Type 2 is the presence of

vacuole A vacuole () is a membrane-bound organelle which is present in Plant cell, plant and Fungus, fungal Cell (biology), cells and some protist, animal, and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water ...

s containing 2 layers of membrane. As Type 1 cells contain

, Type 2 cells contain

and are thought to have similar characteristics as endocrine and neuronal cells.

Synaptic ribbons

Synaptic ribbons are

organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...

s seen in pinealocytes using

electron microscopy An electron microscope is a microscope that uses a beam of electrons as a source of illumination. It uses electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing i ...

. Synaptic ribbons are found in pinealocytes in both children and adults, but are not found in human fetuses. Research on rats has revealed more information about these organelles. The characteristic protein of synaptic ribbons is RIBEYE, as revealed by light and electron microscopy. In lower

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

s, synaptic ribbons serve as a photoreceptive organ, but in upper vertebrates, they serve

secretory Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...

functions within the cell. The presence of proteins such as Munc13-1 indicates that they are important in

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

release. At night, synaptic ribbons of rats appear larger and slightly curved, but during the day, they appear smaller and rod-like.

Evolution of pinealocytes

A common theory on the

evolution Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...

of pinealocytes is that they evolved from

photoreceptor cell A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiation ...

s. It is speculated that in ancestral

s, the pinealocytes served the same function as photoreceptor cells, such as retinal cells; in many non-mammalian vertebrates, pineal cells in the retina are still actively photoreceptive, although these cell do not contribute to a visual image. Structural, functional, and genetic similarities exist between the two cell types. Structurally, both develop from the area of the

designated the

diencephalon In the human brain, the diencephalon (or interbrain) is a division of the forebrain (embryonic ''prosencephalon''). It is situated between the telencephalon and the midbrain (embryonic ''mesencephalon''). The diencephalon has also been known as t ...

, also the area containing the

thalamus The thalamus (: thalami; from Greek language, Greek Wikt:θάλαμος, θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the wikt:dorsal, dorsal part of the diencephalon (a division of ...

and

, during embryological development. Both types of cells have similar features, including

, folded membranes, and

polarity Polarity may refer to: Science *Electrical polarity, direction of electrical current *Polarity (mutual inductance), the relationship between components such as transformer windings *Polarity (projective geometry), in mathematics, a duality of orde ...

. Functional evidence for this theory of evolution can be seen in non-mammalian vertebrates. The retention of photosensitivity of the pinealocytes of lampreys, fish, amphibians, reptiles, and birds and the secretion of

by some of these lower vertebrates suggests that mammalian pinealocytes may have once served as photoreceptor cells. Researchers have also indicated the presence of several photoreceptor proteins found in the

retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...

in the pinealocytes in chicken and fish. Genetic evidence demonstrates that

phototransduction Visual phototransduction is the sensory transduction process of the visual system by which light is detected by photoreceptor cells ( rods and cones) in the vertebrate retina. A photon is absorbed by a retinal chromophore (each bound to an opsin), ...

genes expressed in the photoreceptors of the retina are also present in pinealocytes. More evidence for the evolution of pinealocytes from photoreceptor cells is the similarities between the ribbon complexes in the two types of cells. The presence of the protein RIBEYE and other proteins in both pinealocytes and sensory cells (both photoreceptors and hair cells) suggests that the two cells are related to one another evolutionarily. Differences between the two synaptic ribbons exist in the presence of certain proteins, such as ERC2/CAST1, and the distribution of proteins within the complexes of each cell.

Melatonin

Regulation

Regulation of melatonin synthesis is important to melatonin’s main function in

s. The main molecular control mechanism that exists for melatonin secretion in vertebrates is the enzyme AANAT (arylalkylamine N-acetyltransferase). The expression of the AANAT gene is controlled by the transcription factor pCREB, and this is evident when cells treated with epithalone, a peptide which affects pCREB transcription, have a resulting increase in melatonin synthesis. AANAT is activated through a

protein kinase A In cell biology, protein kinase A (PKA) is a family of serine-threonine kinases whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, in ...

system in which

cyclic AMP Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine triph ...

(cAMP) is involved. The activation of AANAT leads to an increase in melatonin production. Though there are some differences specific to certain species of vertebrates, the effect of cAMP on AANAT and AANAT on melatonin synthesis remains fairly consistent. Melatonin synthesis is also regulated by the nervous system. Nerve fibers in the retinohypothalamic tract connect the retina to the

(SCN). The SCN stimulates the release of

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

from sympathetic nerve fibers from the superior cervical ganglia that synapse with the pinealocytes. Norepinephrine causes the production of melatonin in the pinealocytes by stimulating the production of cAMP. Because the release of norepinephrine from the nerve fibers occurs at night, this system of regulation maintains the body’s circadian rhythms.

Synthesis

Pinealocytes synthesize the hormone melatonin by first converting the amino acid

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

to serotonin. The serotonin is then acetylated by the AANAT enzyme and converted into N-acetylserotonin. N-acetylserotonin is converted into melatonin by the enzyme hydroxyindole O-methyltransferase (HIOMT), also known as

acetylserotonin O-methyltransferase 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 path ...

(ASMT). Activity of these enzymes is high during the night and regulated by the mechanisms previously discussed involving norepinephrine. Synthesis of Melatonin from Serotonin through two enzymatic steps

Synthesis of Melatonin from Serotonin through two enzymatic steps

References

External links

* {{Authority control Endocrine system