Oxytocin
Encyclopedia
Oxytocin (icon) is a mammal
ian hormone
that acts primarily as a neuromodulator in the brain
.
Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth. It is released in large amounts after distension
of the cervix
and uterus
during labor, facilitating birth
, and after stimulation of the nipple
s, facilitating breastfeeding
.
Recent studies have begun to investigate oxytocin's role in various behaviors, including orgasm
, social recognition, pair bond
ing, anxiety
, and maternal behaviors. For this reason, it is sometimes referred to as the "love hormone". The inability to secrete oxytocin and feel empathy is linked to sociopathy, psychopathy, narcissism
and general manipulativeness
.
The word oxytocin was coined from the Greek
ὼκυτοκίνη, ōkytokínē, meaning “quick birth”, after its uterine-contracting properties were discovered by Dale in 1906. The milk ejection property of Oxt was described by Ott and Scott in 1910 and by Schafer and Mackenzie in 1911. The nine amino acid sequence of Oxt was elucidated by Vincent du Vigneaud
et al. and by Tuppy in 1953. and synthesized biochemically soon after by du Vigneaud et al. in 1953. Oxytocin was the very first polypeptide hormone to be sequenced and synthesized.
of nine amino acid
s (a nonapeptide). Its systematic name is cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amine (cys
– tyr
– ile
– gln
– asn
– cys
– pro
– leu
– gly
- NH2, or CYIQNCPLG-NH2). The cysteine residues form a disulfide bond. Oxytocin has a molecular mass
of 1007 daltons. One international unit
(IU) of oxytocin is the equivalent of about 2 microgram
s of pure peptide.
The biologically active form of oxytocin, commonly measured by RIA
and/or HPLC
techniques, is also known as the octapeptide "oxytocin disulfide" (oxidized form), but oxytocin also exists as a reduced dithiol nonapeptide called oxytoceine. It has been theorized that open chain oxytoceine (the reduced form of oxytocin) may also act as a free radical scavenger (by donating an electron to a free radical); oxytoceine may then be oxidized back to oxytocin via the redox potential of dehydroascorbate <---> ascorbate.
The structure of oxytocin is very similar to that of vasopressin
(cys
– tyr
– phe
– gln
– asn
– cys
– pro
– arg
– gly
- NH2), also a nonapeptide with a sulfur bridge, whose sequence differs from oxytocin by 2 amino acids. A table showing the sequences of members of the vasopressin/oxytocin superfamily and the species expressing them is present in the vasopressin
article. Oxytocin and vasopressin were isolated and synthesized by Vincent du Vigneaud
in 1953, work for which he received the Nobel Prize in Chemistry
in 1955.
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.
s. The oxytocin receptor is a G-protein-coupled receptor that requires Mg
2+ and cholesterol
. It belongs to the rhodopsin
-type (class I) group of G-protein-coupled receptors.
for more detail on its action.)
Oxytocin evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security around the mate. Many studies have already shown a correlation of oxytocin with human bonding, increases in trust, and decreases in fear. One study confirmed that there is a positive correlation between oxytocin plasma levels and an anxiety scale measuring the adult romantic attachment. This suggests that oxytocin may be important for the inhibition of brain regions that are associated with behavioral control, fear, and anxiety, thus allowing orgasm to occur.
cannot re-enter the brain because of the blood-brain barrier
. Instead, 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 amygdala
, ventromedial hypothalamus, septum
, nucleus accumbens
, and brainstem.
under the trade names Pitocin and Syntocinon and also as generic
oxytocin. Oxytocin is destroyed in the gastrointestinal tract
, and therefore must be administered by injection or as nasal spray
. Oxytocin has a half-life
of typically about three minutes in the blood. Oxytocin given intravenously
does not enter the brain in significant quantities - it is excluded from the brain by the blood-brain barrier
. There is no evidence for significant central nervous system entry of oxytocin by nasal spray. Oxytocin nasal sprays have been used to stimulate breastfeeding but the efficacy of this approach is doubtful.
Injected oxytocin analogues are used for labor induction and to support labor in case of non-progression of parturition. It has largely replaced ergometrine as the principal agent to increase uterine tone in acute postpartum haemorrhage. Oxytocin is also used in veterinary medicine
to facilitate birth and to stimulate milk release. The tocolytic
agent atosiban
(Tractocile) acts as an antagonist
of oxytocin receptors; this drug is registered in many countries to suppress premature labor between 24 and 33 weeks of gestation. It has fewer side-effects than drugs previously used for this purpose (ritodrine
, salbutamol
, and terbutaline
).
Some have suggested that the trust-inducing property of oxytocin might help those who suffer from social anxieties
and mood disorders, while others have noted the potential for abuse with confidence trick
s and military applications.
The Center of Cognitive Neuroscience in Lyon
, France
concluded that oxytocin may help reduce the negative symptoms of autism
.
have been reported:
Excessive dosage or long term administration (over a period of 24 hours or longer) have been known to result in tetanic uterine contractions, uterine rupture
, postpartum hemorrhage, and water intoxication
, sometimes fatal.
Increased uterine motility has led to the following complications in the fetus/neonate:
In addition, use of pitocin in the mother has been associated with neonatal jaundice
, retinal hemorrhage, and low five-minute Apgar score
.
is synthesized as an inactive precursor protein from the OXT gene
. This precursor protein also includes the oxytocin carrier protein neurophysin I
. The inactive precursor protein is progressively hydrolyzed 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
(PAM).
The activity of the PAM enzyme system is dependent upon ascorbate
, which is a necessary vitamin cofactor. By chance, it was discovered that sodium ascorbate by itself stimulated 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 made in magnocellular neurosecretory cell
s of the supraoptic
and paraventricular
nuclei and is stored in Herring bodies
at the axon terminals in the posterior pituitary. It is then released into the blood from the posterior lobe
(neurohypophysis) of the pituitary gland
. These axons (likely, but dendrites have not been ruled out) have collaterals that innervate oxytocin receptors in the nucleus accumbens
. The peripheral hormonal and behavioral brain effects of oxytocin it has been suggested are coordinated through its common release through these collaterals. Oxytocin is also made 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
and bed nucleus of the stria terminalis.
In the pituitary gland
, oxytocin is packaged in large, dense-core vesicles, where it is bound to neurophysin I
as shown in the inset of the figure; neurophysin is a large peptide
fragment of the larger precursor protein
molecule from which oxytocin is derived by enzymatic
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
s that propagate down axon
s to the nerve endings in the pituitary; the endings contain large numbers of oxytocin-containing vesicles, which are released by exocytosis
when the nerve terminals are depolarised.
, the interstitial cells of Leydig
, the retina, the adrenal medulla, the placenta, 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 different tissues.
endogenously), and in guinea pigs, which, like humans, require an exogenous source of vitamin C (ascorbate) in their diets.
in humans has several allele
s, which differ in their effectiveness. Individuals homozygous for the "G" allele, when compared to carriers of the "A" allele, show higher empathy
, lower stress response, as well as lower prevalence of autism
and of poor parenting skills.
s have an oxytocin-like nonapeptide 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
and are transcribed in opposite directions (however, in fugu
, the homologs are further apart and transcribed in the same directions).
It is thought that the two genes resulted from a gene duplication
event; the ancestral gene is estimated to be about 500 million years old and is found in cyclostomata
(modern members of the Agnatha
).
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
that acts primarily as a neuromodulator in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
.
Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth. It is released in large amounts after distension
Distension
Distension generally refers to an enlargement or ballooning effect:* Gastric distension - bloating of the stomach when air is pumped into it, as in a medical procedure* Abdominal distension - abdominal bloating, a symptom of several medical conditions...
of the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
and uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
during labor, facilitating birth
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...
, and after stimulation of the nipple
Nipple
In its most general form, a nipple is a structure from which a fluid emanates. More specifically, it is the projection on the breasts or udder of a mammal by which breast milk is delivered to a mother's young. In this sense, it is often called a teat, especially when referring to non-humans, and...
s, facilitating breastfeeding
Breastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
.
Recent studies have begun to investigate oxytocin's role in various behaviors, including orgasm
Orgasm
Orgasm is the peak of the plateau phase of the sexual response cycle, characterized by an intense sensation of pleasure...
, social recognition, pair bond
Pair bond
In biology, a pair bond is the strong affinity that develops in some species between the males and females in a pair, potentially leading to breeding. Pair-bonding is a term coined in the 1940s that is frequently used in sociobiology and evolutionary psychology circles...
ing, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, and maternal behaviors. For this reason, it is sometimes referred to as the "love hormone". The inability to secrete oxytocin and feel empathy is linked to sociopathy, psychopathy, narcissism
Narcissism
Narcissism is a term with a wide range of meanings, depending on whether it is used to describe a central concept of psychoanalytic theory, a mental illness, a social or cultural problem, or simply a personality trait...
and general manipulativeness
Manipulation
-As underhand influence:*Crowd manipulation*Data manipulation*Market manipulation*Media manipulation*Parental manipulation*Psychological manipulation-In a physical context:*Card manipulation*Coin manipulation*Hat manipulation*Joint manipulation...
.
The word oxytocin was coined from the Greek
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
ὼκυτοκίνη, ōkytokínē, meaning “quick birth”, after its uterine-contracting properties were discovered by Dale in 1906. The milk ejection property of Oxt was described by Ott and Scott in 1910 and by Schafer and Mackenzie in 1911. The nine amino acid sequence of Oxt was elucidated by Vincent du Vigneaud
Vincent du Vigneaud
Vincent du Vigneaud was an American biochemist. He won a Nobel Prize in Chemistry in 1955 for the isolation, structural identification, and total synthesis of the cyclic peptide, oxytocin.-Biography:...
et al. and by Tuppy in 1953. and synthesized biochemically soon after by du Vigneaud et al. in 1953. Oxytocin was the very first polypeptide hormone to be sequenced and synthesized.
Structure and relation to vasopressin
Oxytocin is a peptidePeptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
of nine amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s (a nonapeptide). Its systematic name is cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amine (cys
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
– tyr
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
– ile
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
– gln
Glutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
– asn
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
– cys
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
– pro
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
– leu
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
– gly
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
- NH2, or CYIQNCPLG-NH2). The cysteine residues form a disulfide bond. Oxytocin has a molecular mass
Molecular mass
The molecular mass of a substance is the mass of one molecule of that substance, in unified atomic mass unit u...
of 1007 daltons. One international unit
International unit
In pharmacology, the International Unit is a unit of measurement for the amount of a substance, based on biological activity or effect. It is abbreviated as IU, as UI , or as IE...
(IU) of oxytocin is the equivalent of about 2 microgram
Microgram
In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...
s of pure peptide.
The biologically active form of oxytocin, commonly measured by RIA
Radioimmunoassay
Radioimmunoassay is a very sensitive in vitro assay technique used to measure concentrations of antigens by use of antibodies...
and/or HPLC
High-performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
techniques, is also known as the octapeptide "oxytocin disulfide" (oxidized form), but oxytocin also exists as a reduced dithiol nonapeptide called oxytoceine. It has been theorized that open chain oxytoceine (the reduced form of oxytocin) may also act as a free radical scavenger (by donating an electron to a free radical); oxytoceine may then be oxidized back to oxytocin via the redox potential of dehydroascorbate <---> ascorbate.
The structure of oxytocin is very similar to that of vasopressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
(cys
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
– tyr
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
– phe
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
– gln
Glutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
– asn
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
– cys
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
– pro
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
– arg
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
– gly
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
- NH2), also a nonapeptide with a sulfur bridge, whose sequence differs from oxytocin by 2 amino acids. A table showing the sequences of members of the vasopressin/oxytocin superfamily and the species expressing them is present in the vasopressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
article. Oxytocin and vasopressin were isolated and synthesized by Vincent du Vigneaud
Vincent du Vigneaud
Vincent du Vigneaud was an American biochemist. He won a Nobel Prize in Chemistry in 1955 for the isolation, structural identification, and total synthesis of the cyclic peptide, oxytocin.-Biography:...
in 1953, work for which he received the Nobel Prize in Chemistry
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
in 1955.
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
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
(CRH) and dynorphin
Dynorphin
Dynorphins are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 , multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neo-endorphin...
, 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.
Actions
Oxytocin has peripheral (hormonal) actions, and also has actions in the brain. The actions of oxytocin are mediated by specific, high-affinity oxytocin receptorOxytocin 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....
s. The oxytocin receptor is a G-protein-coupled receptor that requires Mg
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
2+ and cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
. It belongs to the rhodopsin
Rhodopsin
Rhodopsin, also known as visual purple, is a biological pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light,...
-type (class I) group of G-protein-coupled receptors.
Peripheral (hormonal) actions
The peripheral actions of oxytocin mainly reflect secretion from the pituitary gland. (See oxytocin receptorOxytocin 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....
for more detail on its action.)
- Letdown reflex – in lactatingLactationLactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
(breastfeedingBreastfeedingBreastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
) mothers, oxytocin acts at the mammary glandMammary glandA mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
s, causing milk to be 'let down' into subareolarAreolaThis article is about the breast tissue. For the entomology term, see the glossary of Lepidopteran terms. For an artistic cloud motif, see aureola. For the cactus feature, see Areole....
sinuses, from where it can be excreted via the nippleNippleIn its most general form, a nipple is a structure from which a fluid emanates. More specifically, it is the projection on the breasts or udder of a mammal by which breast milk is delivered to a mother's young. In this sense, it is often called a teat, especially when referring to non-humans, and...
. Sucking by the infantInfantA newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
at the nipple is relayed by spinal nerves to the hypothalamusHypothalamusThe Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. The stimulation causes neurons 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 – important for cervical dilationCervical dilationCervical dilation is the opening of the cervix, the entrance to the uterus, during childbirth, miscarriage, induced abortion, or gynecological surgery...
before birth and causes contractions during the second and third stages of labor. Oxytocin release during breastfeeding causes mild but often painful contractions during the first few weeks of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in knockout miceKnockout mouseA knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
lacking the oxytocin receptor, reproductive behavior and parturition are normal.
- The relationship between oxytocin and human sexual response is unclear. At least two non-controlled studies have found increases in plasmaBlood plasmaBlood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
oxytocin at orgasm – in both men and women. Plasma oxytocin levels are notably increased around the time of self-stimulated orgasm and are still higher than baseline when measured 5 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 that measured oxytocin serum levels in women before and after sexual stimulation, the author suggests that oxytocin serves an important role in sexual arousalSexual arousalSexual arousal, or sexual excitement, is the arousal of sexual desire, during or in anticipation of sexual activity. Things that precipitate human sexual arousal are called erotic stimuli, or colloquially known as turn-ons. There are many potential stimuli, both physical or mental, which can cause...
. This study found that genital tract stimulation resulted in increased oxytocin immediately after orgasm. Another study that reports increases of oxytocin during sexual arousal states that it 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 oxytocin levels were raised throughout sexual arousal and there was no acute increase at orgasm. 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 that these changes "may simply reflect contractile properties on reproductive tissue."
Oxytocin evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security around the mate. Many studies have already shown a correlation of oxytocin with human bonding, increases in trust, and decreases in fear. One study confirmed that there is a positive correlation between oxytocin plasma levels and an anxiety scale measuring the adult romantic attachment. This suggests that oxytocin may be important for the inhibition of brain regions that are associated with behavioral control, fear, and anxiety, thus allowing orgasm to occur.
- Due to its similarity to vasopressinVasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
, it can reduce the excretion of urineUrineUrine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
slightly. In several species, oxytocin can stimulate sodium excretion from the kidneys (natriuresis), and, in humans, high doses of oxytocin can result in hyponatremiaHyponatremiaHyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
.
- Oxytocin and oxytocin receptors are also found in the heartHeartThe heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting cardiomyocyte differentiation. However, the absence of either oxytocin or its receptor in knockout miceKnockout mouseA knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
has not been reported to produce cardiac insufficiencies.
- Modulation of hypothalamic-pituitary-adrenal axisHypothalamic-pituitary-adrenal axisThe hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...
activity. Oxytocin, under certain circumstances, indirectly inhibits release of adrenocorticotropic hormoneAdrenocorticotropic hormoneAdrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
and cortisolCortisolCortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
and, in those situations, may be considered an antagonist of vasopressinVasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
.
- AutismAutismAutism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
. Oxytocin may play a role in autism and may be an effective treatment for autism's repetitive and affiliative behaviors. Oxytocin treatments also resulted in an increased retention of affective speech in adults with autism. Two related studies in adults, in 2003 and 2007, found that oxytocin decreased repetitive behaviors and improved interpretation of emotions. More recently, intranasal administration of oxytocin was found to increase emotion recognition in children as young as 12 who are diagnosed with autism spectrum disorders Oxytocin has also been implicated in the etiology of autism, with one report suggesting that autism is correlated with genomic deletion of the gene containing the oxytocin receptor gene (OXTROxytocin receptorThe 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....
). Studies involving Caucasian and Finnish samples and Chinese Han families provide support for the relationship of OXTR with autism. Autism may also be associated by an aberrant methylation of OXTR, as reported by Gregory and colleagues. After treatment with inhaled oxytocin, autistic patients exhibit more appropriate social behavior. While this research suggests some promise, further clinical trials of oxytocin are required to demonstrate potential benefit and side-effects in the treatment of autism. As such, researchers do not recommend use of oxytocin as a treatment for autism outside of clinical trials.
- Increasing trustTrust (sociology)In a social context, trust has several connotations. Definitions of trust typically refer to a situation characterised by the following aspects: One party is willing to rely on the actions of another party ; the situation is directed to the future. In addition, the trustor abandons control over...
and reducing fearFearFear is a distressing negative sensation induced by a perceived threat. It is a basic survival mechanism occurring in response to a specific stimulus, such as pain or the threat of danger...
. 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 that they were interacting with a computer showed no such reaction, leading to the conclusion that oxytocin was not merely affecting risk-aversion. Nasally administered oxytocin has also been reported to reduce fear, possibly by inhibiting the amygdalaAmygdalaThe ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
(which is thought to be responsible for fear responses). Indeed, studies in rodents have shown that oxytocin can efficiently inhibit fear responses by activating an inhibitory circuit within the amygdala. Some researchers have argued that oxytocin has a general enhancing effect on all social emotions, since intranasal administration of oxytocin also increases envyEnvyEnvy is best defined as a resentful emotion that "occurs when a person lacks another's superior quality, achievement, or possession and either desires it or wishes that the other lacked it."...
and schadenfreudeSchadenfreudeSchadenfreude is pleasure derived from the misfortunes of others. This German word is used as a loanword in English and some other languages, and has been calqued in Danish and Norwegian as skadefryd and Swedish as skadeglädje....
.
- Reducing trust of strangers, and increasing cultural and racial bias.
- Affecting generosityGenerosityGenerosity is the habit of giving freely without expecting anything in return. It can involve offering time, assets or talents to aid someone in need...
by increasing empathy during perspective taking. In a neuroeconomicsNeuroeconomicsNeuroeconomics is an interdisciplinary field that seeks to explain human decision making, the ability to process multiple alternatives and to choose an optimal course of action. It studies how economic behavior can shape our understanding of the brain, and how neuroscientific discoveries can...
experiment, intranasal oxytocin increased generosity in the Ultimatum GameUltimatum gameThe ultimatum game is a game often played in economic experiments in which two players interact to decide how to divide a sum of money that is given to them. The first player proposes how to divide the sum between the two players, and the second player can either accept or reject this proposal. ...
by 80% but has no effect in the Dictator GameDictator gameThe dictator game is a game in experimental economics, similar to the ultimatum game. Experimental results offer evidence against the rationally self-interested individual concept of economic behavior, though precisely what to conclude from the evidence is controversial.-Description:In the...
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 which role they would be in. Serious methodological questions have arisen, however, with regards to the role of oxytocin in trust and generosity.
- Certain learning and memory functions are impaired by centrally administered oxytocin. Also, systemic oxytocin administration can impair memory retrieval in certain aversive memory tasks. Interestingly, oxytocin does seem to facilitate learning and memory specifically for social information. Healthy males administered intranasal oxytocin show improved memory for human faces, in particular happy faces. They also show improved recognition for positive social cues over threatening social cues and improved recognition of fear.
- 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.
Actions within the brain
Oxytocin secreted from the pituitary glandPituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
cannot re-enter the brain because of the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. Instead, 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 amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
, ventromedial hypothalamus, septum
Septum
In anatomy, a septum is a wall, dividing a cavity or structure into smaller ones.-In human anatomy:...
, nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
, and brainstem.
- Sexual arousal. Oxytocin injected into the cerebrospinal fluidCerebrospinal fluidCerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
causes spontaneous erectionErectionPenile erection is a physiological phenomenon where the penis becomes enlarged and firm. Penile erection is the result of a complex interaction of psychological, neural, vascular and endocrine factors, and is usually, though not exclusively, associated with sexual arousal...
s in rats, reflecting actions in the hypothalamus and spinal cord. Centrally administrated oxytocin receptor antagonists can prevent non-contact erections, which is a measure of sexual arousal. Studies using oxytocin antagonists in female rats provide data that oxytocin increases lordosis behaviorLordosis behaviorLordosis behavior, or mammalian lordosis, is a sexual response in mammals, such as mice and cats, that consists of a ventral arching of the spine. During lordosis, the spine curves so that the apex points in the ventral direction. That is, the spine arches inward toward the abdomen.Lordosis aids in...
, indicating an increase in sexual receptivity.
- Bonding. In the Prairie VolePrairie VoleThe Prairie Vole 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...
, oxytocin released into the brain of the female during sexual activity is important for forming a monogamous pair bond with her sexual partner. VasopressinVasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
appears to have a similar effect in males. Oxytocin has a role in social behaviors in many species, and so it seems likely that it also does in humans. In 2003, a study showed that in both humans and dogs oxytocin levels in the blood rose after five to twenty-four minutes of a petting session. It is possible that this plays a role in the emotional bonding between humans and dogs.
- Maternal behaviorMaternal bondThe maternal bond is typically the relationship between a mother and her child.While it typically occurs due to pregnancy and childbirth, it may also occur between a woman and an unrelated child, such as in adoption...
. Female rats given oxytocin antagonistsReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
after giving birth do not exhibit typical maternal behavior. By contrast, virgin female sheep show maternal behavior toward foreign lambs upon cerebrospinal fluidCerebrospinal fluidCerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
infusion of oxytocin, which they would not do otherwise. Oxytocin is involved in the initiation of maternal behavior, not its maintenance; for example, it is higher in mothers after they interact with unfamiliar children rather than their own.
- According to some studies in animals, oxytocin inhibits the development of tolerance to various addictive drugs (opiateOpiateIn medicine, the term opiate describes any of the narcotic opioid alkaloids found as natural products in the opium poppy plant.-Overview:Opiates are so named because they are constituents or derivatives of constituents found in opium, which is processed from the latex sap of the opium poppy,...
s, cocaineCocaineCocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, alcoholEthanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
) and reduces withdrawalWithdrawalWithdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
symptoms.
- Preparing fetal neurons for delivery. Crossing the placenta, maternal oxytocin reaches the fetal brain and induces a switch in the action of neurotransmitter GABAGabâGabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
from excitatory to inhibitory on fetal cortical neurons. This silences the fetal brain for the period of delivery and reduces its vulnerability to hypoxic damageHypoxia (medical)Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
.
- MDMA (ecstasy) may increase feelings of love, empathy, and connection to others by stimulating oxytocin activity via activation of serotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
5-HT1A receptor5-HT1A receptorThe 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...
s, if initial studies in animals apply to humans. The anxiolyticAnxiolyticAn anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
Buspar (buspirone) also appears to produce some or all of its effect via 5-HT1A receptor-induced oxytocin stimulation.
Drug forms
Synthetic oxytocin is sold as proprietary medicationMedication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
under the trade names Pitocin and Syntocinon and also as generic
Generic drug
A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...
oxytocin. Oxytocin is destroyed in the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, and therefore must be administered by injection or as nasal spray
Nasal spray
Nasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
. Oxytocin has a half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
of typically about three minutes in the blood. Oxytocin given intravenously
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
does not enter the brain in significant quantities - it is excluded from the brain by the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. There is no evidence for significant central nervous system entry of oxytocin by nasal spray. Oxytocin nasal sprays have been used to stimulate breastfeeding but the efficacy of this approach is doubtful.
Injected oxytocin analogues are used for labor induction and to support labor in case of non-progression of parturition. It has largely replaced ergometrine as the principal agent to increase uterine tone in acute postpartum haemorrhage. Oxytocin is also used in veterinary medicine
Veterinary medicine
Veterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...
to facilitate birth and to stimulate milk release. The tocolytic
Tocolytic
Tocolytics are medications used to suppress premature labor . They are given when delivery would result in premature birth...
agent atosiban
Atosiban
Atosiban is an inhibitor of the hormones oxytocin and vasopressin. It is used as an intravenous medication as a labour repressant to halt premature labor. Although initial studies suggested it could be used as a nasal spray and hence would not require hospital admission, it is not used in that form...
(Tractocile) acts as an antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
of oxytocin receptors; this drug is registered in many countries to suppress premature labor between 24 and 33 weeks of gestation. It has fewer side-effects than drugs previously used for this purpose (ritodrine
Ritodrine
Ritodrine is a tocolytic drug, was used to stop premature labor. It is available in oral tablets or as an injection, and is typically used as the hydrochloride salt, ritodrine hydrochloride...
, salbutamol
Salbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
, and terbutaline
Terbutaline
Terbutaline is a β2-adrenergic receptor agonist.Terbutaline is currently on the World Anti-Doping Agency's list of prohibited drugs for Olympic athletes, except when administered by inhalation and a Therapeutic Use Exemption has been obtained in advance.Terbutaline is currently used to delay...
).
Some have suggested that the trust-inducing property of oxytocin might help those who suffer from social anxieties
Social anxiety
Social anxiety is anxiety about social situations, interactions with others, and being evaluated or scrutinized by other people...
and mood disorders, while others have noted the potential for abuse with confidence trick
Confidence trick
A confidence trick is an attempt to defraud a person or group by gaining their confidence. A confidence artist is an individual working alone or in concert with others who exploits characteristics of the human psyche such as dishonesty and honesty, vanity, compassion, credulity, irresponsibility,...
s and military applications.
The Center of Cognitive Neuroscience in Lyon
Lyon
Lyon , is a city in east-central France in the Rhône-Alpes region, situated between Paris and Marseille. Lyon is located at from Paris, from Marseille, from Geneva, from Turin, and from Barcelona. The residents of the city are called Lyonnais....
, France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
concluded that oxytocin may help reduce the negative symptoms of autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
.
Potential adverse reactions
Oxytocin is relatively safe when used at recommended doses, and side-effects are uncommon. The following maternal eventsAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
have been reported:
- Subarachnoid hemorrhageSubarachnoid hemorrhageA subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
- Increased heart rateTachycardiaTachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
- Decreased blood pressureHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
- Cardiac arrhythmia and premature ventricular contractionPremature ventricular contractionA premature ventricular contraction , also known as a premature ventricular complex, ventricular premature contraction , ventricular premature beat , or extrasystole, is a relatively common event where the heartbeat is initiated by the heart ventricles rather than by the sinoatrial node, the...
- Impaired uterine blood flow
- Pelvic hematomaHematomaA hematoma, or haematoma, is a localized collection of blood outside the blood vessels, usually in liquid form within the tissue. This distinguishes it from an ecchymosis, which is the spread of blood under the skin in a thin layer, commonly called a bruise...
- Afibrinogenonemia, which can lead to hemorrhage and death
- AnaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
- NauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomitingVomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
Excessive dosage or long term administration (over a period of 24 hours or longer) have been known to result in tetanic uterine contractions, uterine rupture
Uterine rupture
Uterine rupture is a potentially catastrophic event during childbirth by which the integrity of the myometrial wall is breached. In an incomplete rupture the peritoneum is still intact. With a complete rupture the contents of the uterus may spill into the peritoneal cavity or the broad ligament...
, postpartum hemorrhage, and water intoxication
Water intoxication
Water intoxication, also known as water poisoning, is a potentially fatal disturbance in brain functions that results when the normal balance of electrolytes in the body is pushed outside of safe limits by over-consumption of water....
, sometimes fatal.
Increased uterine motility has led to the following complications in the fetus/neonate:
- Decreased heart rateBradycardiaBradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
or heart rate decelerations - Cardiac arrhythmia
- Brain damageBrain damage"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...
- Seizures
- Death
In addition, use of pitocin in the mother has been associated with neonatal jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, retinal hemorrhage, and low five-minute Apgar score
Apgar score
The Apgar score was devised in 1952 by the eponymous Dr. Virginia Apgar as a simple and repeatable method to quickly and summarily assess the health of newborn children immediately after birth...
.
Industrial use
Oxytocin can be administered to bovine animals in order to increase the production of dairy milk.Synthesis, storage, and release
The oxytocin peptidePeptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
is synthesized as an inactive precursor protein from the OXT gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. This precursor protein also includes the oxytocin carrier protein neurophysin I
Neurophysin I
Neurophysin I is a carrier protein with a size of 10 KDa and containing 90 to 97 aminoacids that is a cleavage product of preprooxyphysin...
. The inactive precursor protein is progressively hydrolyzed 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
Peptidylglycine alpha-amidating monooxygenase
Peptidyl-glycine alpha-amidating monooxygenase is an enzyme that in humans is encoded by the PAM gene.-Interactions:Peptidylglycine alpha-amidating monooxygenase has been shown to interact with TSC2.-Further reading:...
(PAM).
The activity of the PAM enzyme system is dependent upon ascorbate
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
, which is a necessary vitamin cofactor. By chance, it was discovered that sodium ascorbate by itself stimulated 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
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
.
Neural sources
In the hypothalamusHypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, oxytocin is made in magnocellular neurosecretory cell
Magnocellular neurosecretory cell
Magnocellular neurosecretory cells are large 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 one being the nucleus circularis...
s of the supraoptic
Supraoptic nucleus
The supraoptic nucleus is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm...
and paraventricular
Paraventricular nucleus
The paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
nuclei and is stored in Herring bodies
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
Posterior pituitary
The posterior pituitary comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Despite its name, the posterior pituitary gland is not a gland, per se; rather, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior...
(neurohypophysis) of the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
. These axons (likely, but dendrites have not been ruled out) have collaterals that innervate oxytocin receptors in the nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
. The peripheral hormonal and behavioral brain effects of oxytocin it has been suggested are coordinated through its common release through these collaterals. Oxytocin is also made 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
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
and bed nucleus of the stria terminalis.
In the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
, oxytocin is packaged in large, dense-core vesicles, where it is bound to neurophysin I
Neurophysin I
Neurophysin I is a carrier protein with a size of 10 KDa and containing 90 to 97 aminoacids that is a cleavage product of preprooxyphysin...
as shown in the inset of the figure; neurophysin is a large peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
fragment of the larger precursor protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
molecule from which oxytocin is derived by enzymatic
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
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
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
s that propagate down axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s to the nerve endings in the pituitary; the endings contain large numbers of oxytocin-containing vesicles, which are released by exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
when the nerve terminals are depolarised.
Non-neural sources
Outside the brain, oxytocin-containing cells have been identified in several diverse tissues including the corpus luteumCorpus luteum
The corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...
, the interstitial cells of Leydig
Leydig cell
Leydig cells, also known as interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle. They produce testosterone in the presence of luteinizing hormone...
, the retina, the adrenal medulla, the placenta, 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 different tissues.
Female
Oxytocin is synthesized by corpora lutea of several species, including ruminants and primates. Along with estrogen, it is involved in inducing the endometrial synthesis of prostaglandin F2α to cause regression of the corpus luteum.Male
The Leydig cells in some species have also been shown to possess the biosynthetic machinery to manufacture testicular oxytocin de novo, to be specific, in rats (which can synthesize Vitamin CVitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
endogenously), and in guinea pigs, which, like humans, require an exogenous source of vitamin C (ascorbate) in their diets.
Oxytocin receptor polymorphism
The oxytocin receptorOxytocin 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 humans has several allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s, which differ in their effectiveness. Individuals homozygous for the "G" allele, when compared to carriers of the "A" allele, show higher empathy
Empathy
Empathy is the capacity to recognize and, to some extent, share feelings that are being experienced by another sapient or semi-sapient being. Someone may need to have a certain amount of empathy before they are able to feel compassion. The English word was coined in 1909 by E.B...
, lower stress response, as well as lower prevalence of autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and of poor parenting skills.
Evolution
Virtually all vertebrateVertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s have an oxytocin-like nonapeptide 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
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
and are transcribed in opposite directions (however, in fugu
Fugu
is the Japanese word for pufferfish and the dish prepared from it, normally species of genus Takifugu, Lagocephalus, or Sphoeroides, or porcupinefish of the genus Diodon. Fugu can be lethally poisonous due to its tetrodotoxin; therefore, it must be carefully prepared to remove toxic parts and to...
, the homologs are further apart and transcribed in the same directions).
It is thought that the two genes resulted from a gene duplication
Gene duplication
Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...
event; the ancestral gene is estimated to be about 500 million years old and is found in cyclostomata
Cyclostomata
Cyclostomata is a group of chordates that comprises the living jawless fishes: the lampreys and hagfishes. Both groups have round mouths that lack jaws but have retractable horny teeth...
(modern members of the Agnatha
Agnatha
Agnatha is a superclass of jawless fish in the phylum Chordata, subphylum Vertebrata. The group excludes all vertebrates with jaws, known as gnathostomes....
).
External links
- Hug the Monkey - A weblog devoted entirely to oxytocin
- The Soft Machine - Review of oxytocin and bonding in animal and human research (.pdf)
- A Neurophysiologic Model of the Circuitry of Oxytocin in Arousal, Female Distress and Depression - Rainer K. Liedtke, MD (2004)
- Oxytocin.org - 'I get a kick out of you: Scientists are finding that, after all, love really is down to a chemical addiction between people', The Economist (February 12, 2004)
- NewScientist.com - 'Release of Oxytocin due to penetrative sex reduces stress and neurotic tendencies', New Scientist (January 26, 2006)
- SMH.com.au - 'To sniff at danger: Inhalable oxytocin could become a cure for social fears', Boston Globe (January 12, 2006)
- New Scientist -'Cuddle chemical' could treat mental illness (14 May 2008)
- Molecular neurobiology of social bonding: Implications for autism spectrum disorders a lecture by Prof. Larry Young, Jan. 4, 2010.
- A TED talk by Prof.Paul Zak on Trust,Morality & Oxytocin