Oxytocin (Oxt or OT) is a

peptide hormone Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...

and

neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

normally produced in the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

and released by the

posterior pituitary The posterior pituitary (or neurohypophysis) is the posterior lobe of the pituitary gland which is part of the endocrine system. The posterior pituitary is not glandular as is the anterior pituitary. Instead, it is largely a collection of axonal ...

. It plays a role in social bonding,

reproduction Reproduction (or procreation or breeding) is the biological process by which new individual organisms – "offspring" – are produced from their "parent" or parents. Reproduction is a fundamental feature of all known life; each individual or ...

childbirth Childbirth, also known as labour and delivery, is the ending of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or caesarean section. In 2019, there were about 140.11 million births globall ...

, and the period after childbirth. Oxytocin is released into the bloodstream as a hormone in response to

sexual activity Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their sexuality. People engage in a variety of sexual acts, ranging from activities done alone (e.g., masturbation) ...

and during labour. It is also available in

pharmaceutical form Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration (such as a cap ...

. In either form, oxytocin stimulates uterine contractions to speed up the process of childbirth. In its natural form, it also plays a role in bonding with the baby and

milk production A dairy is a business enterprise established for the harvesting or processing (or both) of animal milk – mostly from cows or buffaloes, but also from goats, sheep, horses, or camels – for human consumption. A dairy is typically located on ...

. Production and secretion of oxytocin is controlled by a

positive feedback Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the ...

mechanism, where its initial release stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases. A similar process takes place during lactation and during sexual activity. Oxytocin is derived by

enzymatic Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

splitting from the

peptide precursor A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein (or peptide) that can be turned into an active form by post-translational modification, such as breaking off a piece of the molecule or adding on another molecule ...

encoded by the human OXT

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The deduced structure of the active nonapeptide is: : Cys – Tyr –

Ile Ile may refer to: * iLe, a Puerto Rican singer * Ile District (disambiguation), multiple places * Ilé-Ifẹ̀, an ancient Yoruba city in south-western Nigeria * Interlingue (ISO 639:ile), a planned language * Isoleucine, an amino acid * Anothe ...

– Gln – Asn – Cys –

Pro Pro is an abbreviation meaning "professional". Pro, PRO or variants thereof may also refer to: People * Miguel Pro (1891–1927), Mexican priest * Pro Hart (1928–2006), Australian painter * Mlungisi Mdluli (born 1980), South African retired f ...

– Leu –

Gly Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

– NH₂, or CYIQNCPLG-NH₂.

Etymology

The term "oxytocin" derives from the Greek "ὠκυτόκος" (''ōkutókos''), based on ὀξύς (oxús), meaning "sharp" or "swift", and τόκος (tókos), meaning "childbirth". The adjective form is "oxytocic", which refers to medicines which stimulate uterine contractions, to speed up the process of childbirth.

History

The uterine-contracting properties of the principle that would later be named oxytocin were discovered by British pharmacologist

Henry Hallett Dale Sir Henry Hallett Dale (9 June 1875 – 23 July 1968) was an English pharmacologist and physiologist. For his study of acetylcholine as agent in the chemical transmission of nerve pulses (neurotransmission) he shared the 1936 Nobel Prize in Ph ...

in 1906, and its milk ejection property was described by Ott and Scott in 1910 and by Schafer and Mackenzie in 1911. In the 1920s, oxytocin and

vasopressin Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...

were isolated from pituitary tissue and given their current names. Oxytocin's molecular structure was determined in 1952. In the early 1950s, American biochemist

Vincent du Vigneaud Vincent du Vigneaud (May 18, 1901 – December 11, 1978) was an American biochemist. He was recipient of the 1955 Nobel Prize in Chemistry "for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypep ...

found that oxytocin is made up of nine amino acids, and he identified its amino acid sequence, the first polypeptide hormone to be sequenced. In 1953, du Vigneaud carried out the synthesis of oxytocin, the first polypeptide hormone to be synthesized. Du Vigneaud was awarded the Nobel Prize in 1955 for his work. Further work on different synthetic routes for oxytocin, as well as the preparation of analogues of the hormone (''e.g.'' 4-deamido-oxytocin) was performed in the following decade by Iphigenia Photaki.

Biochemistry

Estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

has been found to increase the

secretion 440px 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 ...

of oxytocin and to increase the

expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...

of its

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

, the

oxytocin receptor The oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin. In humans, the oxytocin receptor is encoded by the ''OXTR'' gene which has been localized to human chromosome 3p25 ...

, in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

. In women, a single dose of

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...

has been found to be sufficient to increase circulating oxytocin concentrations.

Biosynthesis

Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone (CRH) and dynorphin, for example, that act locally. The magnocellular neurons that make oxytocin are adjacent to magnocellular neurons that make vasopressin, and are similar in many respects. The biosynthesis of the different forms of OT

The oxytocin

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

is synthesized as an inactive precursor protein from the ''OXT''

. This precursor protein also includes the oxytocin carrier protein

neurophysin I Neurophysin I is a carrier protein with a size of 10 K Da and contains 90 to 97 amino acids. It is a cleavage product (formed by splitting of a compound molecule into a simpler one) of preprooxyphysin. It is a neurohypophysial hormone that is tra ...

. The inactive precursor protein is progressively

hydrolyzed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

into smaller fragments (one of which is neurophysin I) via a series of enzymes. The last hydrolysis that releases the active oxytocin nonapeptide is catalyzed by

peptidylglycine alpha-amidating monooxygenase Peptidyl-glycine alpha-amidating monooxygenase is an enzyme that catalyzes the conversion of glycine amides to amides and glyoxylate. The enzyme is involved in the biosynthesis of many signaling peptides and some fatty acid amides. In humans, t ...

(PAM). The activity of the PAM enzyme system is dependent upon

vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...

(ascorbate), which is a necessary vitamin cofactor. By chance, sodium ascorbate by itself was found to stimulate the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner. Many of the same tissues (''e.g.'' ovaries, testes, eyes, adrenals, placenta, thymus, pancreas) where PAM (and oxytocin by default) is found are also known to store higher concentrations of vitamin C. Oxytocin is known to be metabolized by the

oxytocinase Oxytocinase is a type of enzyme that metabolizes the endogenous neuropeptide, oxytocin. The most well-characterized oxytocinase is leucyl/cystinyl aminopeptidase, which is also an enkephalinase. Other oxytocinases are also known. During pregnancy, o ...

leucyl/cystinyl aminopeptidase Leucyl/cystinyl aminopeptidase, also known as cystinyl aminopeptidase (CAP), insulin-regulated aminopeptidase (IRAP), human placental leucine aminopeptidase (PLAP), oxytocinase, and vasopressinase, is an enzyme of the aminopeptidase group that in ...

. Other oxytocinases are also known to exist.

Amastatin Amastatin, also known as 3-amino-2-hydroxy-5-methylhexanoyl-L-valyl-L-valyl-L-aspartic acid, is a naturally occurring, competitive and reversible aminopeptidase inhibitor that was isolated from ''Streptomyces sp. ME 98-M3''. It specifically inhi ...

bestatin Ubenimex (INN), also known more commonly as bestatin, is a competitive, reversible protease inhibitor. It is an inhibitor of arginyl aminopeptidase (aminopeptidase B), leukotriene A4 hydrolase (a zinc metalloprotease that displays both epoxide ...

(ubenimex),

leupeptin Leupeptin, also known as ''N''-acetyl-L-leucyl-L-leucyl-L-argininal, is a naturally occurring protease inhibitor that can inhibit cysteine, serine and threonine peptidases. It is often used during ''in vitro'' experiments when a specific enzymati ...

, and

puromycin Puromycin is an antibiotic protein synthesis inhibitor which causes premature chain termination during translation. Inhibition of translation Puromycin is an aminonucleoside antibiotic, derived from the '' Streptomyces alboniger'' bacterium, ...

have been found to inhibit the enzymatic degradation of oxytocin, though they also inhibit the degradation of various other peptides, such as

met-enkephalin Met-enkephalin, also known as metenkefalin (INN), sometimes referred to as opioid growth factor (OGF), is a naturally occurring, endogenous opioid peptide that has opioid effects of a relatively short duration. It is one of the two forms of enkep ...

, and

dynorphin A Dynorphin A is a dynorphin, an endogenous opioid peptide with the amino acid sequence: Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys. Dynorphin A1–8 is a truncated form of dynorphin A with the amino acid sequence: Tyr-Gly-Gly-Phe-Leu-Ar ...

Neural sources

In the

, oxytocin is made in

magnocellular neurosecretory cell Magnocellular neurosecretory cells are large neuroendocrine cells within the supraoptic nucleus and paraventricular nucleus of the hypothalamus. They are also found in smaller numbers in accessory cell groups between these two nuclei, the largest ...

s of the supraoptic and paraventricular nuclei, and is stored in

Herring bodies Herring bodies or neurosecretory bodies are structures found in the posterior pituitary. They represent the terminal end of the axons from the hypothalamus, and hormones are temporarily stored in these locations. They are neurosecretory terminals ...

at the axon terminals in the posterior pituitary. It is then released into the blood from the

posterior lobe The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebe ...

(neurohypophysis) of the

pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...

. These

axons An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, th ...

(likely, but

dendrites Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...

have not been ruled out) have collaterals that innervate neurons in the

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for "nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypotha ...

, a brain structure where oxytocin receptors are expressed. The

endocrine The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...

effects of hormonal oxytocin and the cognitive or behavioral effects of oxytocin

s are thought to be coordinated through its common release through these collaterals. Oxytocin is also produced by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord. Depending on the species, oxytocin receptor-expressing cells are located in other areas, including the

amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...

and

bed nucleus of the stria terminalis The stria terminalis (or terminal stria) is a structure in the brain consisting of a band of fibers running along the lateral margin of the ventricular surface of the thalamus. Serving as a major output pathway of the amygdala, the stria termina ...

. In the pituitary gland, oxytocin is packaged in large, dense-core vesicles, where it is bound to

as shown in the inset of the figure; neurophysin is a large

fragment of the larger precursor

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

molecule from which oxytocin is derived by

cleavage. Secretion of oxytocin from the neurosecretory nerve endings is regulated by the electrical activity of the oxytocin cells in the hypothalamus. These cells generate

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

s that propagate down

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...

s to the nerve endings in the pituitary; the endings contain large numbers of oxytocin-containing vesicles, which are released by

exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...

when the nerve terminals are depolarised.

Non-neural sources

Endogenous oxytocin concentrations in the brain have been found to be as much as 1000-fold higher than peripheral levels. Outside the brain, oxytocin-containing cells have been identified in several diverse tissues, including in females in the

corpus luteum The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...

and the placenta; in males in the testicles' interstitial cells of Leydig; and in both sexes in the retina, the adrenal medulla, the thymus and the pancreas. The finding of significant amounts of this classically " neurohypophysial" hormone outside the central nervous system raises many questions regarding its possible importance in these diverse tissues.

Male

The

Leydig cells Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...

in some species have been shown to possess the biosynthetic machinery to manufacture testicular oxytocin ''de novo'', to be specific, in rats (which can synthesize vitamin C endogenously), and in guinea pigs, which, like humans, require an exogenous source of vitamin C (ascorbate) in their diets.

Female

Oxytocin is synthesized by

corpora lutea The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is ...

of several species, including ruminants and primates. Along with estrogen, it is involved in inducing the endometrial synthesis of prostaglandin F_2α to cause regression of the corpus luteum.

Evolution

Virtually all

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

s have an oxytocin-like

nonapeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

hormone that supports reproductive functions and a vasopressin-like nonapeptide hormone involved in water regulation. The two genes are usually located close to each other (less than 15,000 bases apart) on the same

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

, and are transcribed in opposite directions (however, in

fugu The fugu (; ; ) in Japanese, ''bogeo'' (; 鰒魚) or ''bok'' () in Korean, and ''hétún'' (河豚; 河魨) in Standard Modern Chinese is a pufferfish, normally of the genus ''Takifugu'', ''Lagocephalus'', or ''Sphoeroides'', or a porcupinefish ...

, the homologs are further apart and transcribed in the same direction). The two genes are believed to result from a

gene duplication Gene duplication (or chromosomal duplication or gene amplification) is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. ...

event; the ancestral gene is estimated to be about 500 million years old and is found in

cyclostomata Cyclostomi, often referred to as Cyclostomata , is a group of vertebrates that comprises the living jawless fishes: the lampreys and hagfishes. Both groups have jawless mouths with horny epidermal structures that function as teeth called ceratod ...

(modern members of the

Agnatha Agnatha (, Ancient Greek 'without jaws') is an infraphylum of jawless fish in the phylum Chordata, subphylum Vertebrata, consisting of both present (cyclostomes) and extinct ( conodonts and ostracoderms) species. Among recent animals, cyclosto ...

Biological function

Oxytocin has peripheral (hormonal) actions, and also has actions in the brain. Its actions are mediated by specific

s. The oxytocin receptor is a

G-protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

, OT-R, which requires

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...

and

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

and is expressed in myometrial cells. It belongs to the rhodopsin-type (class I) group of G-protein-coupled receptors. Studies have looked at oxytocin's role in various behaviors, including

orgasm Orgasm (from Greek , ; "excitement, swelling") or sexual climax is the sudden discharge of accumulated sexual excitement during the sexual response cycle, resulting in rhythmic, involuntary muscular contractions in the pelvic region charac ...

, social recognition,

pair bond In biology, a pair bond is the strong affinity that develops in some species between a mating pair, often leading to the production and rearing of offspring and potentially a lifelong bond. Pair-bonding is a term coined in the 1940s that is freque ...

ing,

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

, in-group

bias Bias is a disproportionate weight ''in favor of'' or ''against'' an idea or thing, usually in a way that is closed-minded, prejudicial, or unfair. Biases can be innate or learned. People may develop biases for or against an individual, a group, ...

, situational lack of

honesty Honesty or truthfulness is a facet of moral character that connotes positive and virtuous attributes such as integrity, truthfulness, straightforwardness, including straightforwardness of conduct, along with the absence of lying, cheating, theft, ...

autism The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...

, and maternal behaviors. Oxytocin is believed to have a significant role in social learning. There are indicators that oxytocin may help to decrease noise in the brain's auditory system, increase perception of social cues and support more targeted social behavior. It may also enhance reward responses. However, its effects may be influenced by context, such as the presence of familiar or unfamiliar individuals.

Physiological

The

peripheral A peripheral or peripheral device is an auxiliary device used to put information into and get information out of a computer. The term ''peripheral device'' refers to all hardware components that are attached to a computer and are controlled by the ...

actions of oxytocin mainly reflect secretion from the

. The behavioral effects of oxytocin are thought to reflect release from centrally projecting oxytocin neurons, different from those that project to the pituitary gland, or that are collaterals from them. Oxytocin receptors are expressed by neurons in many parts of the brain and spinal cord, including the

ventromedial hypothalamus The ventromedial nucleus of the hypothalamus (VMN, also sometimes referred to as the ventromedial hypothalamus, VMH) is a nucleus of the hypothalamus. "The ventromedial hypothalamus (VMH) is a distinct morphological nucleus involved in terminatin ...

septum In biology, a septum (Latin for ''something that encloses''; plural septa) is a wall, dividing a cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate. Examples Human anatomy * Interatri ...

, and

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

, although the distribution differs markedly between species. Furthermore, the distribution of these receptors changes during development and has been observed to change after

parturition Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the f ...

in the

montane vole The montane vole (''Microtus montanus'') is a species of vole native to the western United States and Canada. Description Montane voles are medium-sized voles, with a total length of , including the tail. Adults typically weigh anything from , ...

. *

Milk ejection reflex Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...

/Letdown reflex: in lactating (

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

) mothers, oxytocin acts at the

mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in primat ...

s, causing milk to be 'let down' into

lactiferous duct Lactiferous ducts are ducts that converge and form a branched system connecting the nipple to the lobules of the mammary gland. When lactogenesis occurs, under the influence of hormones, the milk is moved to the nipple by the action of smooth mus ...

s, from where it can be excreted via the

nipple The nipple is a raised region of tissue on the surface of the breast from which, in females, milk leaves the breast through the lactiferous ducts to feed an infant. The milk can flow through the nipple passively or it can be ejected by smooth mu ...

. Suckling by the

infant An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

at the

is relayed by

spinal nerves A spinal nerve is a mixed nerve, which carries motor, sensory, and autonomic signals between the spinal cord and the body. In the human body there are 31 pairs of spinal nerves, one on each side of the vertebral column. These are grouped into the ...

to the

. The

stimulation Stimulation is the encouragement of development or the cause of activity generally. For example, "The press provides stimulation of political discourse." An interesting or fun activity can be described as "stimulating", regardless of its physica ...

causes

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

that make oxytocin to fire action potentials in intermittent bursts; these bursts result in the secretion of pulses of oxytocin from the neurosecretory nerve terminals of the pituitary gland. *

Uterine contraction Uterine contractions are muscle contractions of the uterine smooth muscle that occur during the menstrual cycle and labour. Uterine contractions occur throughout the menstrual cycle in the non-pregnant state and throughout gestation. Throughout m ...

: important for

cervical dilation Cervical dilation (or cervical dilatation) is the opening of the cervix, the entrance to the uterus, during childbirth, miscarriage, induced abortion, or gynecological surgery. Cervical dilation may occur naturally, or may be induced surgically o ...

before birth, oxytocin causes contractions during the second and third stages of

labor Labour or labor may refer to: * Childbirth, the delivery of a baby * Labour (human activity), or work ** Manual labour, physical work ** Wage labour, a socioeconomic relationship between a worker and an employer ** Organized labour and the labour ...

. Oxytocin release during

causes mild but often painful

contraction Contraction may refer to: Linguistics * Contraction (grammar), a shortened word * Poetic contraction, omission of letters for poetic reasons * Elision, omission of sounds ** Syncope (phonology), omission of sounds in a word * Synalepha, merged ...

s during the first few weeks of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in

knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

lacking the oxytocin receptor, reproductive

behavior Behavior (American English) or behaviour (British English) is the range of actions and mannerisms made by individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as wel ...

and

are normal. *In male rats, oxytocin may induce

erection An erection (clinically: penile erection or penile tumescence) is a physiological phenomenon in which the penis becomes firm, engorged, and enlarged. Penile erection is the result of a complex interaction of psychological, neural, vascular, ...

s. A burst of oxytocin is released during ejaculation in several species, including human males; its suggested function is to stimulate contractions of the reproductive tract, aiding

sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...

release. * Human sexual response: Oxytocin levels in

plasma Plasma or plasm may refer to: Science * Plasma (physics), one of the four fundamental states of matter * Plasma (mineral), a green translucent silica mineral * Quark–gluon plasma, a state of matter in quantum chromodynamics Biology * Blood pla ...

rise during sexual stimulation and orgasm. At least two uncontrolled studies have found increases in plasma oxytocin at orgasm – in both men and women. Plasma oxytocin levels are increased around the time of self-stimulated orgasm and are still higher than baseline when measured five minutes after self arousal. The authors of one of these studies speculated that oxytocin's effects on muscle contractibility may facilitate sperm and egg transport. :In a study measuring oxytocin serum levels in women before and after

sexual stimulation Sexual stimulation is any stimulation, stimulus (including bodily contact) that leads to, enhances and maintains sexual arousal, and may lead to orgasm. Although sexual arousal may arise without physical stimulation, achieving orgasm usually requ ...

, the author suggests it serves an important role in

sexual arousal Sexual arousal (also known as sexual excitement) describes the physiological and psychological responses in preparation for sexual intercourse or when exposed to sexual stimuli. A number of physiological responses occur in the body and mind as ...

. This study found genital tract stimulation resulted in increased oxytocin immediately after orgasm. Another study reported increases of oxytocin during sexual arousal could be in response to nipple/areola, genital, and/or genital tract stimulation as confirmed in other mammals. Murphy et al. (1987), studying men, found that plasma oxytocin levels remain unchanged during sexual arousal, but that levels increase sharply after ejaculation, returning to baseline levels within 30 minutes. In contrast,

was increased during arousal but returned to baseline at the time of ejaculation. The study concludes that (in males) vasopressin is secreted during arousal, while oxytocin is only secreted after ejaculation. A more recent study of men found an increase in plasma oxytocin immediately after orgasm, but only in a portion of their sample that did not reach statistical significance. The authors noted these changes "may simply reflect contractile properties on reproductive tissue". * Due to its similarity to

, it can reduce the excretion of

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

slightly, and so it can be classified as an

antidiuretic An antidiuretic is a substance that helps to control fluid balance in an animal's body by reducing urination, opposing diuresis. Its effects are opposite that of a diuretic. The major endogenous antidiuretics are antidiuretic hormone (ADH; also ca ...

. In several species, oxytocin can stimulate sodium excretion from the kidneys (natriuresis), and, in humans, high doses can result in low sodium levels (

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...

). * Cardiac effects: oxytocin and oxytocin receptors are also found in the

heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...

in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting

cardiomyocyte Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...

differentiation. However, the absence of either oxytocin or its receptor in knockout mice has not been reported to produce cardiac insufficiencies. * Modulation of hypothalamic-pituitary-adrenal axis activity: oxytocin, under certain circumstances, indirectly inhibits release of

adrenocorticotropic hormone Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...

and

cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...

and, in those situations, may be considered an antagonist of vasopressin. * Preparing fetal neurons for delivery (in rats): crossing the placenta, maternal oxytocin reaches the fetal brain and induces a switch in the action of neurotransmitter GABA from excitatory to inhibitory on fetal cortical neurons. This silences the fetal brain for the period of delivery and reduces its vulnerability to hypoxic damage. *Feeding: a 2012 paper suggested that oxytocin neurons in the para-ventricular hypothalamus in the brain may play a key role in suppressing appetite under normal conditions and that other hypothalamic neurons may trigger eating via inhibition of these oxytocin neurons. This population of oxytocin neurons is absent in Prader-Willi syndrome, a genetic disorder that leads to uncontrollable feeding and obesity, and may play a key role in its pathophysiology. Research on the oxytocin-related neuropeptide asterotocin in

starfish Starfish or sea stars are star-shaped echinoderms belonging to the class Asteroidea (). Common usage frequently finds these names being also applied to ophiuroids, which are correctly referred to as brittle stars or basket stars. Starfish ...

also showed that in echinoderms, the chemical induces muscle relaxation, and in starfish specifically caused the organisms to evert their stomach and react as though feeding on prey, even when none were present.

Psychological

* Autism: Oxytocin has been implicated in the etiology of autism, with one report suggesting autism is correlated to a mutation on the oxytocin receptor gene ( ''OXTR''). Studies involving Caucasian, Finnish and Chinese Han families provide support for the relationship of ''OXTR'' with autism. Autism may also be associated with an aberrant methylation of ''OXTR''. * Protection of brain functions: Studies in rats have demonstrated that nasal application of oxytocin can alleviate impaired learning capabilities caused by restrained stress. The authors attributed this effect to an improved hippocampal response in Brain-Derived Neurotrophic Factor (BDNF) being observed. Accordingly, oxytocin has been shown to promote neural growth in the hippocampus in rats even during swim stress or glucocorticoid administration. In a mouse model of early onset of Alzheimer's, the administration of oxytocin by a gel particularly designed to make the peptide accessible for the brain, the cognitive decline and hippocampal atrophy of these mice were delayed. Moreover, the amyloid β-protein deposit and nerve cell apoptosis were retarded. An observed inhibitory impact by oxytocin on the inflammatory activity of the microglia was proposed to be an important factor.

Bonding

In the

prairie vole The prairie vole (''Microtus ochrogaster'') is a small vole found in central North America. The vole has long, coarse grayish-brown fur on the upper portion of the body and yellowish fur on the lower portion of the body. It has short ears and a ...

, oxytocin released into the brain of the female during sexual activity is important for forming a pair bond with her sexual partner.

Vasopressin Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...

appears to have a similar effect in males. Oxytocin has a role in social behaviors in many species, so it likely also does in humans. In a 2003 study, both humans and dog oxytocin levels in the blood rose after a five to 24 minute petting session. This possibly plays a role in the emotional bonding between humans and dogs. * Maternal behavior: Female rats given oxytocin

antagonists An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

after giving birth do not exhibit typical maternal behavior. By contrast, virgin female sheep show maternal behavior toward foreign lambs upon

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

infusion of oxytocin, which they would not do otherwise. Oxytocin is involved in the initiation of human maternal behavior, not its maintenance; for example, it is higher in mothers after they interact with unfamiliar children rather than their own. *Human

ingroup In sociology and social psychology, an in-group is a social group to which a person self-categorization theory, psychologically identifies as being a member. By contrast, an out-group is a social group with which an individual does not identify. ...

bonding: Oxytocin can increase positive attitudes, such as bonding, toward individuals with similar characteristics, who then become classified as "in-group" members, whereas individuals who are dissimilar become classified as "out-group" members. Race can be used as an example of in-group and out-group tendencies because society often categorizes individuals into groups based on race (Caucasian, African American, Latino, etc.). One study that examined race and

empathy Empathy is the capacity to understand or feel what another person is experiencing from within their frame of reference, that is, the capacity to place oneself in another's position. Definitions of empathy encompass a broad range of social, co ...

found that participants receiving nasally administered oxytocin had stronger reactions to pictures of in-group members making pained faces than to pictures of out-group members with the same expression. Moreover, individuals of one race may be more inclined to help individuals of the same race than individuals of another race when they are experiencing pain. Oxytocin has also been implicated in

lying A lie is an assertion that is believed to be false, typically used with the purpose of deception, deceiving or Deception, misleading someone. The practice of communicating lies is called lying. A person who communicates a lie may be termed a l ...

when lying would prove beneficial to other in-group members. In a study where such a relationship was examined, it was found that when individuals were administered oxytocin, rates of

dishonesty Dishonesty is to act without honesty. It is used to describe a lack of probity, cheating, lying, or deliberately withholding information, or being deliberately deceptive or a lack in integrity, knavishness, perfidiosity, corruption or treacherousne ...

in the participants' responses increased for their in-group members when a beneficial outcome for their group was expected. Both of these examples show the tendency of individuals to act in ways that benefit those considered to be members of their social group, or in-group. Oxytocin is not only correlated with the preferences of individuals to associate with members of their own group, but it is also evident during conflicts between members of different groups. During conflict, individuals receiving nasally administered oxytocin demonstrate more frequent defense-motivated responses toward in-group members than out-group members. Further, oxytocin was correlated with participant desire to protect vulnerable in-group members, despite that individual's attachment to the conflict. Similarly, it has been demonstrated that when oxytocin is administered, individuals alter their subjective preferences in order to align with in-group ideals over out-group ideals. These studies demonstrate that oxytocin is associated with intergroup dynamics. Further, oxytocin influences the responses of individuals in a particular group to those of another group. The in-group bias is evident in smaller groups; however, it can also be extended to groups as large as one's entire country leading toward a tendency of strong national zeal. A study done in the Netherlands showed that oxytocin increased the in-group favoritism of their nation while decreasing acceptance of members of other ethnicities and foreigners. People also show more affection for their country's flag while remaining indifferent to other cultural objects when exposed to oxytocin. It has thus been hypothesized that this hormone may be a factor in

xenophobic Xenophobia () is the fear or dislike of anything which is perceived as being foreign or strange. It is an expression of perceived conflict between an in-group and out-group and may manifest in suspicion by the one of the other's activities, a ...

tendencies secondary to this effect. Thus, oxytocin appears to affect individuals at an international level where the in-group becomes a specific "home" country and the out-group grows to include all other countries.

Drugs

Drug interaction Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, ...

: According to several studies in animals, oxytocin inhibits the development of

tolerance Tolerance or toleration is the state of tolerating, or putting up with, conditionally. Economics, business, and politics * Toleration Party, a historic political party active in Connecticut * Tolerant Systems, the former name of Veritas Software ...

to various addictive drugs (

opiate An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonis ...

cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

), and reduces

withdrawal Withdrawal means "an act of taking out" and may refer to: * Anchoresis (withdrawal from the world for religious or ethical reasons) * ''Coitus interruptus'' (the withdrawal method) * Drug withdrawal * Social withdrawal * Taking of money from a ban ...

symptoms.

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...

(ecstasy) may increase feelings of love, empathy, and connection to others by stimulating oxytocin activity primarily via activation of

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

5-HT1A receptor The serotonin 1A receptor (or 5-HT1A receptor) is a subtype of serotonin receptor, or 5-HT receptor, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protei ...

s, if initial studies in animals apply to humans. The

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...

drug

buspirone Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder. Benefits support its short-term use. It is taken by mouth, and it may take up to fo ...

may produce some of its effects via 5-HT1A receptor-induced oxytocin stimulation as well. *

Addiction vulnerability Addiction vulnerability is an individual's risk of developing an addiction during their lifetime. There are a range of genetic and environmental risk factors for developing an addiction that vary across the population. Genetic and environmental r ...

: Concentrations of endogenous oxytocin can impact the effects of various drugs and one's susceptibility to

substance use disorder Substance use disorder (SUD) is the persistent use of drugs (including alcohol) despite substantial harm and adverse consequences as a result of their use. Substance use disorders are characterized by an array of mental/emotional, physical, and ...

s, with higher concentrations associated with lower susceptibility. The status of the endogenous oxytocin system can enhance or reduce susceptibility to addiction through its bidirectional interaction with numerous systems, including the

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

system, the

hypothalamic–pituitary–adrenal axis The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components: the hypothalamus (a part of the brain located below the thalamus), the pituitary gland (a ...

and the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

. Individual differences in the endogenous oxytocin system based on genetic predisposition, gender and environmental influences, may therefore affect

addiction vulnerability Addiction vulnerability is an individual's risk of developing an addiction during their lifetime. There are a range of genetic and environmental risk factors for developing an addiction that vary across the population. Genetic and environmental r ...

. Oxytocin may be related to the place conditioning behaviors observed in habitual drug abusers.

Fear and anxiety

Oxytocin is typically remembered for the effect it has on

prosocial behavior Prosocial behavior, or intent to benefit others, is a social behavior that "benefit other people or society as a whole", "such as helping, sharing, donating, co-operating, and volunteering". Obeying the rules and conforming to socially accepted ...

s, such as its role in facilitating trust and attachment between individuals. However, oxytocin has a more complex role than solely enhancing prosocial behaviors. There is consensus that oxytocin modulates

fear Fear is an intensely unpleasant emotion in response to perceiving or recognizing a danger or threat. Fear causes physiological changes that may produce behavioral reactions such as mounting an aggressive response or fleeing the threat. Fear ...

and

; that is, it does not directly elicit fear or anxiety. Two dominant theories explain the role of oxytocin in fear and anxiety. One theory states that oxytocin increases approach/avoidance to certain social stimuli and the second theory states that oxytocin increases the salience of certain social stimuli, causing the animal or human to pay closer attention to socially relevant stimuli. Nasally administered oxytocin has been reported to reduce

, possibly by inhibiting the

(which is thought to be responsible for fear responses). Indeed, studies in rodents have shown oxytocin can efficiently inhibit fear responses by activating an inhibitory circuit within the amygdala. Some researchers have argued oxytocin has a general enhancing effect on all social emotions, since intranasal administration of oxytocin also increases

envy Envy is an emotion which occurs when a person lacks another's quality, skill, achievement, or possession and either desires it or wishes that the other lacked it. Aristotle defined envy as pain at the sight of another's good fortune, stirred b ...

and ''

Schadenfreude Schadenfreude (; ; 'harm-joy') is the experience of pleasure, joy, or self-satisfaction that comes from learning of or witnessing the troubles, failures, or humiliation of another. It is a borrowed word from German, with no direct translation ...

''. Individuals who receive an intranasal dose of oxytocin identify facial expressions of disgust more quickly than individuals who do not receive oxytocin. Facial expressions of disgust are evolutionarily linked to the idea of contagion. Thus, oxytocin increases the salience of cues that imply contamination, which leads to a faster response because these cues are especially relevant for survival. In another study, after administration of oxytocin, individuals displayed an enhanced ability to recognize expressions of fear compared to the individuals who received the placebo. Oxytocin modulates fear responses by enhancing the maintenance of social memories. Rats that are genetically modified to have a surplus of oxytocin receptors display a greater fear response to a previously conditioned stressor. Oxytocin enhances the aversive social memory, leading the rat to display a greater fear response when the aversive stimulus is encountered again.

Mood and depression

Oxytocin produces

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

-like effects in

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

s of depression, and a deficit of it may be involved in the

pathophysiology Pathophysiology ( physiopathology) – a convergence of pathology with physiology – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the ...

of depression in humans. The antidepressant-like effects of oxytocin are not blocked by a selective antagonist of the oxytocin receptor, suggesting that these effects are not mediated by the oxytocin receptor. In accordance, unlike oxytocin, the selective non-peptide oxytocin receptor agonist

WAY-267,464 WAY-267464 is a potent, selective, non-peptide agonist for the oxytocin receptor, with negligible affinity for the vasopressin receptors. Contradictorily however, though originally described as selective for the oxytocin receptor and lacking aff ...

does not produce antidepressant-like effects, at least in the

tail suspension test The tail suspension test (TST) is an experimental method used in scientific research to measure stress in rodents. It is based on the observation that if a mouse is subjected to short term inescapable stress then the mouse will become immobile ...

. In contrast to WAY-267,464,

carbetocin Carbetocin, sold under the brand names Pabal among others, is a medication used to prevent excessive bleeding after childbirth, particularly following Cesarean section. It appears to work as well as oxytocin. Due to it being less economical than ...

, a close analogue of oxytocin and peptide oxytocin receptor agonist, notably does produce antidepressant-like effects in animals. As such, the antidepressant-like effects of oxytocin may be mediated by modulation of a different target, perhaps the vasopressin V_1A receptor where oxytocin is known to weakly bind as an agonist. Oxytocin mediates the antidepressant-like effects of sexual activity. A drug for

sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction as ...

sildenafil Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by ...

enhances electrically evoked oxytocin release from the

. In accordance, it may have promise as an antidepressant.

Sex differences

It has been shown that oxytocin differentially affects males and females. Females who are administered oxytocin are overall faster in responding to socially relevant stimuli than males who received oxytocin. Additionally, after the administration of oxytocin, females show increased

activity in response to threatening scenes; however, males do not show increased amygdala activation. This phenomenon can be explained by looking at the role of

gonadal hormones Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects are ...

, specifically

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

, which modulate the enhanced threat processing seen in females. Estrogen has been shown to stimulate the release of oxytocin from the

and promote receptor binding in the amygdala. It has also been shown that testosterone directly suppresses oxytocin in mice. This has been hypothesized to have evolutionary significance. With oxytocin suppressed, activities such as hunting and attacking invaders would be less mentally difficult as oxytocin is strongly associated with empathy.

Social

* Affecting

generosity Generosity (also called largess) is the virtue of being liberal in giving, often as gifts. Generosity is regarded as a virtue by various world religions and philosophies, and is often celebrated in cultural and religious ceremonies. Scientific in ...

by increasing empathy during perspective taking: In a

neuroeconomics Neuroeconomics is an interdisciplinary field that seeks to explain human decision-making, the ability to process multiple alternatives and to follow through on a plan of action. It studies how economic behavior can shape our understanding of the ...

experiment,

intranasal Nasal administration, popularly known as snorting, is a route of administration in which drugs are insufflated through the nose. It can be a form of either topical administration or systemic administration, as the drugs thus locally delivered ...

oxytocin increased generosity in the

Ultimatum Game The ultimatum game is a game that has become a popular instrument of economic experiments. An early description is by Nobel laureate John Harsanyi in 1961. One player, the proposer, is endowed with a sum of money. The proposer is tasked with spl ...

by 80%, but had no effect in the

Dictator Game The dictator game is a popular experimental instrument in social psychology and economics, a derivative of the ultimatum game. The term "game" is a misnomer because it captures a decision by a single player: to send money to another or not. Thus, t ...

that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experiment explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants into which role they would be placed. Serious methodological questions have arisen, however, with regard to the role of oxytocin in trust and generosity. Empathy in healthy males has been shown to be increased after intranasal oxytocin This is most likely due to the effect of oxytocin in enhancing eye gaze. There is some discussion about which aspect of empathy oxytocin might alter – for example, cognitive vs. emotional empathy. While studying wild chimpanzees, it was noted that after a chimpanzee shared food with a non-kin related chimpanzee, the subjects' levels of oxytocin increased, as measured through their urine. In comparison to other cooperative activities between chimpanzees that were monitored including grooming, food sharing generated higher levels of oxytocin. This comparatively higher level of oxytocin after food sharing parallels the increased level of oxytocin in nursing mothers, sharing nutrients with their kin. *

Trust Trust often refers to: * Trust (social science), confidence in or dependence on a person or quality It may also refer to: Business and law * Trust law, a body of law under which one person holds property for the benefit of another * Trust (bus ...

is increased by oxytocin. Study found that with the oxytocin nasal spray, people place more trust to strangers in handling their money. Disclosure of emotional events is a sign of trust in humans. When recounting a negative event, humans who receive

oxytocin share more emotional details and stories with more emotional significance. Humans also find faces more trustworthy after receiving intranasal oxytocin. In a study, participants who received intranasal oxytocin viewed photographs of human faces with neutral expressions and found them to be more trustworthy than those who did not receive oxytocin. This may be because oxytocin reduces the fear of social betrayal in humans. Even after experiencing social alienation by being excluded from a conversation, humans who received oxytocin scored higher in trust on the

Revised NEO Personality Inventory The Revised NEO Personality Inventory (NEO PI-R) is a personality inventory that assesses an individual on five dimensions of personality, the so-called Big Five personality traits. These traits are openness to experience, conscientiousness, ex ...

. Moreover, in a risky investment game, experimental subjects given nasally administered oxytocin displayed "the highest level of trust" twice as often as the control group. Subjects who were told they were interacting with a computer showed no such reaction, leading to the conclusion that oxytocin was not merely affecting

risk aversion In economics and finance, risk aversion is the tendency of people to prefer outcomes with low uncertainty to those outcomes with high uncertainty, even if the average outcome of the latter is equal to or higher in monetary value than the more ce ...

. When there is a reason to be distrustful, such as experiencing betrayal, differing reactions are associated with

(

OXTR The oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin. In humans, the oxytocin receptor is encoded by the ''OXTR'' gene which has been localized to human chromosome 3p ...

) differences. Those with the CT

haplotype A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...

experience a stronger reaction, in the form of anger, to betrayal. * Romantic attachment: In some studies, high levels of

oxytocin have been correlated with romantic attachment. For example, if a couple is separated for a long period of time, anxiety can increase due to the lack of physical affection. Oxytocin may aid romantically attached couples by decreasing their feelings of anxiety when they are separated. *Group-serving dishonesty/deception: In a carefully controlled study exploring the biological roots of immoral behavior, oxytocin was shown to promote dishonesty when the outcome favored the group to which an individual belonged instead of just the individual. * Oxytocin affects

social Social organisms, including human(s), live collectively in interacting populations. This interaction is considered social whether they are aware of it or not, and whether the exchange is voluntary or not. Etymology The word "social" derives from ...

distance between adult males and females, and may be responsible at least in part for

romantic attraction Romance or romantic love is a feeling of love for, or a strong attraction towards another person, and the courtship behaviors undertaken by an individual to express those overall feelings and resultant emotions. The ''Wiley Blackwell Encycl ...

and subsequent

monogamous Monogamy ( ) is a form of Dyad (sociology), dyadic Intimate relationship, relationship in which an individual has only one Significant other, partner during their lifetime. Alternately, only one partner at any one time (Monogamy#Serial monogamy, ...

pair bonding. An oxytocin nasal spray caused men in a monogamous relationship, but not single men, to increase the distance between themselves and an attractive woman during a first encounter by 10 to 15 centimeters. The researchers suggested that oxytocin may help promote fidelity within monogamous relationships. For this reason, it is sometimes referred to as the "bonding hormone". There is some evidence that oxytocin promotes

ethnocentric Ethnocentrism in social science and anthropology—as well as in colloquial English discourse—means to apply one's own culture or ethnicity as a frame of reference to judge other cultures, practices, behaviors, beliefs, and people, instead of ...

behavior, incorporating the trust and empathy of in-groups with their suspicion and rejection of outsiders. Furthermore, genetic differences in the

gene (OXTR) have been associated with maladaptive social traits such as aggressive behavior. *

Social behavior Social behavior is behavior among two or more organisms within the same species, and encompasses any behavior in which one member affects the other. This is due to an interaction among those members. Social behavior can be seen as similar to an ...

and

wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...

: Oxytocin is also thought to modulate

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

by decreasing certain

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

. Thus, the increased release in oxytocin following positive social interactions has the potential to improve wound healing. A study by Marazziti and colleagues used heterosexual couples to investigate this possibility. They found increases in plasma oxytocin following a social interaction were correlated with faster wound healing. They hypothesized this was due to oxytocin reducing inflammation, thus allowing the wound to heal more quickly. This study provides preliminary evidence that positive social interactions may directly influence aspects of health. According to a study published in 2014, silencing of oxytocin receptor interneurons in the medial prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice during the sexually receptive phase of the estrous cycle. * Oxytocin evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security when in the company of the mate. This suggests oxytocin may be important for the inhibition of the brain regions associated with behavioral control, fear, and anxiety, thus allowing orgasm to occur. Research has also demonstrated that oxytocin can decrease anxiety and protect against

stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...

, particularly in combination with social support. It is found, that

endocannabinoid Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

signaling mediates oxytocin-driven social reward. According to a study published in 2008, its results pointed to how a lack of oxytocin in mice saw a abnormalities in emotional behavior. Another study in conducted in 2014, saw similar results with a variation in the oxytocin receptor is connected with dopamine transporter and how levels of oxytocin are dependent on the levels of dopamine transporter levels. One study explored the effects of low levels of oxytocin and the other on possible explanation of what affects oxytocin receptors. As a lack of social skills and proper emotional behavior are common signs of Autism, low levels of oxytocin could become a new sign for individuals that fall into the Autism Spectrum.

Chemistry

Oxytocin is a

of nine

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s (a

) in the sequence cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amide ( Cys – Tyr –

– Gln – Asn – Cys –

– Leu –

– NH₂, or CYIQNCPLG-NH₂); its ''C''-terminus has been converted to a

primary amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

and a

disulfide bridge In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

joins the cysteine moieties. Oxytocin has a

molecular mass The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quanti ...

of 1007 Da, and one

international unit In pharmacology, the international unit (IU) is a unit of measurement for the effect, not mass of a substance; the variance is based on the biological activity or effect, for the purpose of easier comparison across similar ''forms'' of substance ...

(IU) of oxytocin is the equivalent of 1.68 μg of pure peptide. While the structure of oxytocin is highly conserved in placental mammals, a novel structure of oxytocin was reported in 2011 in

marmoset The marmosets (), also known as zaris or sagoin, are 22 New World monkey species of the genera ''Callithrix'', ''Cebuella'', ''Callibella'', and ''Mico''. All four genera are part of the biological family Callitrichidae. The term "marmoset" is ...

tamarin The tamarins are squirrel-sized New World monkeys from the family Callitrichidae in the genus ''Saguinus''. They are the first offshoot in the Callitrichidae tree, and therefore are the sister group of a clade formed by the lion tamarins, Goel ...

s, and other new world

primates Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...

. Genomic sequencing of the gene for oxytocin revealed a single in-frame mutation (

thymine Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nu ...

for

cytosine Cytosine () ( symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an am ...

) which results in a single amino acid substitution at the 8-position (

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

for

leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...

). Since this original Lee ''et al.'' paper, two other laboratories have confirmed Pro8-OT and documented additional oxytocin structural variants in this primate taxon. Vargas-Pinilla ''et al.'' sequenced the coding regions of the OXT gene in other genera in new world primates and identified the following variants in addition to Leu8- and Pro8-OT: Ala8-OT, Thr8-OT, and Val3/Pro8-OT. Ren ''et al.'' identified a variant further, Phe2-OT in

howler monkey Howler monkeys (genus ''Alouatta'', monotypic in subfamily Alouattinae) are the most widespread primate genus in the Neotropics and are among the largest of the platyrrhines along with the muriquis (''Brachyteles''), the spider monkeys (''Ateles' ...

s. The biologically active form of oxytocin, commonly measured by

RIA A ria (; gl, ría) is a coastal inlet formed by the partial submergence of an unglaciated river valley. It is a drowned river valley that remains open to the sea. Definitions Typically rias have a Drainage system (geomorphology)#Dendritic dr ...

and/or

HPLC High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...

techniques, is the oxidized octapeptide oxytocin disulfide, but oxytocin also exists as a reduced straight-chain (non-cyclic)

dithiol In organic chemistry, a dithiol is a type of organosulfur compound with two thiol () functional groups. Their properties are generally similar to those of monothiols in terms of solubility, odor, and volatility. They can be classified according ...

nonapeptide called oxytoceine. It has been theorized that oxytoceine may act as a

free radical A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing. Ageing Ailments of unknown cause Biogerontology Biological processes Causes of death Cellular processes Gerontology Life extension Metabo ...

scavenger, as donating an electron to a free radical allows oxytoceine to be re-oxidized to oxytocin via the

dehydroascorbate Dehydroascorbic acid (DHA) is an oxidized form of ascorbic acid (vitamin C). It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbate by glutathione and ot ...

ascorbate Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) and ...

redox couple. Recent advances in analytical instrumental techniques highlighted the importance of liquid chromatography (LC) coupled with mass spectrometry (MS) for measuring oxytocin levels in various samples derived from biological sources. Most of these studies optimized the oxytocin quantification in electrospray ionization (ESI) positive mode, using +Hsup>+ as the parent ion at mass-to-charge ratio (''m/z'') 1007.4 and the fragment ions as diagnostic peaks at ''m/z'' 991.0, ''m/z'' 723.2 and ''m/z'' 504.2. These important ion selections paved the way for the development of current methods of oxytocin quantification using MS instrumentation. The structure of oxytocin is very similar to that of

. Both are nonapeptides with a single disulfide bridge, differing only by two substitutions in the amino acid sequence (differences from oxytocin bolded for clarity): Cys – Tyr – Phe – Gln – Asn – Cys – Pro –

Arg Arg or ARG may refer to: Places *''Arg'' () means "citadel" in Persian, and may refer to: **Arg, Iran, a village in Fars Province, Iran **Arg (Kabul), presidential palace in Kabul, Afghanistan **Arg, South Khorasan, a village in South Khorasan P ...

– Gly – NH₂. Oxytocin and vasopressin were isolated and their

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes ...

reported in 1954, work for which

was awarded the 1955

Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...

with the citation: "for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypeptide hormone." Oxytocin and vasopressin are the only known hormones released by the human

posterior pituitary gland The posterior pituitary (or neurohypophysis) is the posterior lobe of the pituitary gland which is part of the endocrine system. The posterior pituitary is not glandular as is the anterior pituitary. Instead, it is largely a collection of axona ...

to act at a distance. However, oxytocin neurons make other peptides, including

corticotropin-releasing hormone Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a peptide hormone involved in stress (biology), stress responses. It is a releasing ...

and

dynorphin Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, a ...

, for example, that act locally. The

s that make oxytocin are adjacent to magnocellular neurosecretory cells that make vasopressin. These are large neuroendocrine neurons which are excitable and can generate action potentials.

In popular culture

"Oxytocin" is the name of the fifth song on

Billie Eilish Billie Eilish Pirate Baird O'Connell ( ; born December 18, 2001) is an American singer-songwriter. She first gained public attention in 2015 with her debut single " Ocean Eyes", written and produced by her brother Finneas O'Connell, with whom ...

's second album ''

Happier Than Ever ''Happier Than Ever'' is the second studio album by American singer Billie Eilish, released by Darkroom and Interscope Records on July 30, 2021. Eilish co-wrote the album with her brother and frequent collaborator Finneas O'Connell, who also p ...

''. In the novel '' The Fireman'' by Joe Hill, the hormone plays a role in neutralizing the danger posed by an infectious spore that causes a condition known as Dragonscale. If the spore enters an oxytocin-rich environment, it will enter a dormant state instead of causing its host to undergo

spontaneous human combustion Spontaneous human combustion (SHC) is the pseudoscientific concept of the combustion of a living (or recently deceased) human body without an apparent external source of ignition. In addition to reported cases, descriptions of the alleged phen ...

. The formula for Oxytocin is displayed as written on the fingers of

Nina Zilli Maria Chiara Fraschetta (born 2 February 1980), better known by her stage name Nina Zilli (), is an Italian singer-songwriter. After releasing her debut single "50mila", she achieved commercial success with the album '' Sempre lontano'', released ...

and appears in the opening shot of her video for "Sola". Jack (Steve Zahn), a character in the 2004 movie “Employee of the Month” explains how oxytocin performs in the female body at the 45m27s mark. A more detailed explanation on oxytocin begins at 44m40s.

References

External links

* {{Authority control Antidiuretics Breastfeeding Hormones of the hypothalamus Hormones of the pregnant female Human female endocrine system Interpersonal attraction Neuropeptides Neurotransmitters Orgasm Oxytocin receptor agonists Posterior pituitary hormones Vasopressin receptor agonists Orphan drugs

Etymology

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