Oxytocin
222300
224356618
2008-07-08T14:21:36Z
68.94.231.139
/* Drug forms */
{{drugbox
| IUPAC_name = 3-(19-amino-13-sec-butyl-7-
(carboxymethyl)-4-(2-(1-(carboxymethylamino)-5-
guanidino-1-oxopentan-2-ylcarbamoyl)
pyrrolidine-1-carbonyl)-16-(4-hydroxybenzyl)-
6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-
pentaazacycloicosan-10-yl)propanoic acid
| image = Oxytocin.svg
| width = 300px
| image2 = Oxytocin3d.png
| CAS_number = 50-56-6
| ATC_prefix = H01
| ATC_suffix = BB02
| PubChem = 439302
| DrugBank = BTD00016
| C = 43 | H = 66 | N = 12 | O = 12 | S = 2
| molecular_weight = 1007.19 g/mol
| bioavailability = nil
| protein_bound = 30%
| metabolism = hepatic oxytocinases
| elimination_half-life = 1-6 min
| excretion = Biliary and [[Kidney|renal]]
| pregnancy_AU = A
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = [[Nasal spray|Intranasal]], [[Intravenous therapy|IV]], [[Intramuscular injection|IM]]
}}
'''Oxytocin''' ([[IPA]]: {{IPA|/ˌɔk.sɪ.ˈtoʊ.sɪn/}}) (Greek, "quick birth") is a [[mammal]]ian [[hormone]] that also acts as a [[neurotransmitter]] in the [[brain]].
It is best known for its roles in female reproduction: it is released in large amounts after distension of the [[cervix]] and [[vagina]] during labor, and after stimulation of the [[nipple]]s, facilitating [[childbirth|birth]] and [[breastfeeding]], respectively. Recent studies have begun to investigate oxytocin's role in various behaviors, including social recognition and bonding, anxiety, and maternal behaviors.
==Synthesis, storage and release==
Oxytocin is made in [[magnocellular neurosecretory cell]]s in the [[supraoptic nucleus]] and [[paraventricular nucleus]] of the [[hypothalamus]] and is released into the blood from the [[posterior pituitary|posterior lobe]] of the [[pituitary gland]]. Oxytocin is also made by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord.
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 [[enzyme|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.
Oxytocin is also synthesized by [[corpora lutea]] of several species, including ruminants and primates. Along with estrogen, it is involved in inducing the endometrial synthesis of Prostaglandin-F2alpha to cause regression of the corpus luteum.
===Structure and relation to vasopressin===
Oxytocin is a [[peptide]] of nine [[amino acid]]s (a nonapeptide). The sequence is [[cysteine]] - [[tyrosine]] - [[isoleucine]] - [[glutamine]] - [[asparagine]] - [[cysteine]] - [[proline]] - [[leucine]] - [[glycine]] (CYIQNCPLG). The cysteine residues form a [[sulfur bridge]]. Oxytocin has a [[molecular mass]] of 1007 [[dalton (unit)|dalton]]s. One [[international unit]] (IU) of oxytocin is the equivalent of about 2 [[microgram]]s of pure peptide.
[[Image:Oxytocin.jpg|thumb|240px|left|Oxytocin structure. Inset shows oxytocin bound to neurophysin]]
The structure of oxytocin is very similar to that of [[vasopressin]] ([[cysteine]] - [[tyrosine]] - <u>[[phenylalanine]]</u> - [[glutamine]] - [[asparagine]] - [[cysteine]] - [[proline]] - <u>[[arginine]]</u> - [[glycine]]), 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.
==Actions==
{{protein
| Name = oxytocin, prepro- (neurophysin I)
| caption =
| image =
| width =
| HGNCid = 8528
| Symbol = OXT
| AltSymbols = OT
| EntrezGene = 5020
| OMIM = 167050
| RefSeq = NM_000915
| UniProt = P01178
| PDB =
| ECnumber =
| Chromosome = 20
| Arm = p
| Band = 13
| LocusSupplementaryData =
}}
Oxytocin has peripheral (hormonal) actions, and also has actions in the brain. The actions of oxytocin are mediated by specific, high affinity oxytocin receptors. The oxytocin receptor is a [[G-protein-coupled receptor]] which requires [[magnesium|Mg]]<sup>2+</sup> and [[cholesterol]]. It belongs to the [[rhodopsin]]-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 receptor]] for more detail on its action.)
*[[Breastfeeding|Letdown reflex]] – in [[lactation|lactating]] (breastfeeding) mothers, oxytocin acts at the [[mammary gland]]s, causing milk to be 'let down' into a collecting chamber, from where it can be extracted by compressing the [[areola]] and sucking at the [[nipple]]. Sucking by the [[infant]] at the nipple is relayed by spinal nerves to the [[hypothalamus]]. 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 dilation]] before birth and causes contractions during the second and third stages of [[labor (childbirth)|labor]]. Oxytocin release during breastfeeding causes mild but often painful uterine 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 mouse|knockout mice]] lacking the oxytocin receptor, reproductive behavior and [[parturition]] is normal.<ref name="Takayanagi">Takayanagi Y ''et al.'' (2005) Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. ''Proc Natl Acad Sci USA'' 102:16096-101 PMID 16249339</ref>
*The relationship between oxytocin and human sexual response is unclear. At least two non-controlled studies have found increases in [[blood plasma|plasma]] oxytocin at orgasm – in both men and women.<ref name="carm1987">Carmichael MS, Humbert R, Dixen J, Palmisano G, Greenleaf W, Davidson JM (1987). "Plasma oxytocin increases in the human sexual response," ''J Clin Endocrinol Metab'' 64:27-31 PMID 3782434</ref><ref>Carmichael MS, Warburton VL, Dixen J & Davidson JM (1994). "Relationship among cardiovascular, muscular, and oxytocin responses during human sexual activity," ''Archives of Sexual Behavior'' 23 59–79.</ref> The authors of one of these studies speculated that oxytocin's effects on muscle contractibility may facilitate sperm and egg transport.<ref name="carm1987" /> Murphy et al. (1987), studying men, found that oxytocin levels were raised throughout sexual arousal and there was no acute increase at orgasm. <ref>Murphy ME, Seckl JR, Burton S, Checkley SA & Lightman SL (1987). "Changes in oxytocin and vasopressin secretion during sexual activity in men," ''Journal of Clinical Endocrinology and Metabolism'' 65:738–741.</ref> 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."<ref>Kruger THC, Haake P, Chereath D, Knapp W, Janssen OE, Exton MS, Schedlowski M & Hartmann U (2003). "Specificity of the neuroendocrine response to orgasm during sexual arousal in men," ''Journal of Endocrinology'' 177:57–64</ref>
*Due to its similarity to [[vasopressin]], it can reduce the excretion of [[urine]] slightly. More important, in several species, oxytocin can stimulate sodium excretion from the kidneys (natriuresis), and in humans, high doses of oxytocin can result in [[hyponatremia]].
*Oxytocin and oxytocin receptors are also found in the [[heart]] in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting [[cardiomyocyte]] differentiation. <ref>Paquin J ''et al.''(2002) Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes. ''Proc Natl Acad Sci USA'' 99:9550-5 PMID 12093924</ref><ref>Jankowski ''et al.'' (2004) Oxytocin in cardiac ontogeny. ''Proc Natl Acad Sci USA'' 101:13074-9 [http://www.pnas.org/cgi/content/full/101/35/13074 online] PMID 15316117</ref> However, the absence of either oxytocin or its receptor in [[knockout mouse|knockout mice]] has not been reported to produce cardiac insufficiencies.<ref name="Takayanagi" />
*Modulation of [[hypothalamic-pituitary-adrenal axis]] activity. Oxytocin, under certain circumstances, indirectly inhibits release of [[adrenocorticotropic hormone]] and [[cortisol]] and, in those situations, may be considered an antagonist of [[vasopressin]]. <ref>[[Walenty Hartwig]] - Practical Endocrinology, ISBN 83-200-1415-8 </ref>
===Actions of oxytocin within the brain===<!-- This section is linked from [[Zoophilia]] -->
Oxytocin secreted from the pituitary gland 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. Oxytocin receptors are expressed by neurons in many parts of the brain and spinal cord, including the [[amygdala]], [[ventromedial hypothalamus]], [[septum]] and [[brainstem]].
* Sexual arousal. Oxytocin injected into the [[cerebrospinal fluid]] causes spontaneous [[erection]]s in rats,<ref name="Gimpl">Gimpl G, Fahrenholz F. (2001) The oxytocin receptor system: structure, function, and regulation. ''Physiological Reviews'' 81: [http://physrev.physiology.org/cgi/content/full/81/2/629 full text] PMID 11274341</ref> reflecting actions in the hypothalamus and spinal cord.
* Bonding. In the [[Prairie Vole]], oxytocin released into the brain of the female during sexual activity is important for forming a monogamous pair bond with her sexual partner. [[Vasopressin]] appears to have a similar effect in males.<ref>[http://www.americanscientist.org/template/AssetDetail/assetid/14756 Vacek M, High on Fidelity. What can voles teach us about monogamy? ]</ref> Oxytocin has a role in social behaviors in many species, and so it seems likely that it has similar roles in humans.
* [[Autism]]. A 1998 study found significantly lower levels of oxytocin in blood plasma of autistic children.<ref>{{cite journal |journal= Biol Psychiatry |year=1998 |volume=43 |issue=4 |pages=270–7 |title= Plasma oxytocin levels in autistic children |author= Modahl C, Green L, Fein D ''et al.'' |doi=0.1016/S0006-3223(97)00439-3 |pmid=9513736 |doi_brokendate= 2008-06-28}}</ref> A 2003 study found a decrease in autism spectrum repetitive behaviors when oxytocin was administered intravenously.<ref>{{cite journal |journal= Neuropsychopharmacology |year=2003 |volume=28 |issue=1 |pages=193–8 |title= Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders |author= Hollander E, Novotny S, Hanratty M ''et al.'' |url=http://www.nature.com/npp/journal/v28/n1/full/1300021a.html |doi=10.1038/sj.npp.1300021 |pmid=12496956}}</ref> A 2007 study reported that oxytocin helped autistic adults retain the ability to evaluate the emotional significance of speech intonation.<ref>{{cite journal |journal= Biol Psychiatry |year=2007 |volume=61 |issue=4 |pages=498–503 |title= Oxytocin increases retention of social cognition in autism |author= Hollander E, Bartz J, Chaplin W ''et al.'' |doi=10.1016/j.biopsych.2006.05.030 |pmid=16904652}}</ref> This also may be similar to the effect of oxytocin on evaluation of face valence.<ref name="Petrovic">Predrag Petrovic, Raffael Kalisch, Tania Singer and Raymond J Dolan,''Oxytocin Attenuates Affective Evaluations of Conditioned Faces and Amygdala Activity'', [[Journal of Neuroscience]], online June 25, 2008.</ref>
*[[Maternal bond|Maternal behavior]]. Rat females given oxytocin [[Receptor antagonist|antagonists]] after giving birth do not exhibit typical maternal behavior.<ref>{{cite journal |journal= Journal of Endocrinology
|year=1987 |volume=112 |issue=2 |pages=275–282 |title= Inhibition of post-partum maternal behaviour in the rat by injecting an oxytocin antagonist into the cerebral ventricles |author= Van Leengoed E, Kerker E, Swanson HH |url=http://joe.endocrinology-journals.org/cgi/content/abstract/112/2/275 |pmid= 3819639}}</ref> By contrast, virgin female sheep show maternal behavior towards foreign lambs upon [[cerebrospinal fluid]] infusion of oxytocin, which they would not do otherwise. <ref>[http://neuroendo.org.uk/index.php/content/view/34/11/ Kendrick KM, The Neurobiology of Social Bonds]</ref>
*Increasing [[Trust (sociology)|trust]] and reducing fear. 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]].<ref>Kosfeld M ''et al.'' (2005) Oxytocin increases trust in humans. ''[[Nature (journal)|Nature]]'' 435:673-676. [http://www.iew.unizh.ch/home/kosfeld/papers/ottrust_nature.pdf PDF] PMID 15931222</ref> Nasally administered oxytocin has also been reported to reduce fear, possibly by inhibiting the [[amygdala]] (which is thought to be responsible for fear responses).<ref>Kirsch P ''et al.'' (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. ''J Neurosci'' 25:11489-93 PMID 16339042</ref> There is no conclusive evidence for access of oxytocin to the brain through intranasal administration, however.
*Affecting [[generosity]] by increasing empathy during perspective taking. In a [[neuroeconomics]] experiment, intranasal oxytocin increased generosity in the [[Ultimatum Game]] by 80% but has no effect in the [[Dictator Game]] 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.<ref> Zak, P.J. Stanton, A.A., Ahmadi, A. 2007. Oxytocin increases generosity in humans. ''[[PloS ONE (journal)|PLoS ONE]]'' 2(11): e1128. [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001128] </ref>
*According to some studies in animals, oxytocin inhibits the development of tolerance to various addictive drugs ([[opiate]]s, [[cocaine]], [[ethanol|alcohol]]) and reduces [[withdrawal]] symptoms.<ref>Kovacs GL, Sarnyai Z, Szabo G. (1998) Oxytocin and addiction: a review. ''Psychoneuroendocrinology'' 23:945-62 PMID 9924746</ref>
*Preparing fetal neurons for delivery. 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 [[hypoxia (medical)|hypoxic damage]].<ref>Tyzio R ''et al.''(2006) Maternal Oxytocin Triggers a Transient Inhibitory Switch in GABA Signaling in the Fetal Brain During Delivery. ''Science'' 314: 1788-1792 PMID 17170309</ref>
*Certain learning and memory functions are impaired by centrally administered oxytocin.<ref name="Gimpl" />. Also, systemic oxytocin administration can impair memory retrieval in certain aversive memory tasks. <ref> de Oliveira LF, Camboim C, Diehl F, Consiglio AR, Quillfeldt JA. Glucocorticoid-mediated effects of systemic oxytocin upon memory retrieval. ''Neurobiology of Learning and Memory.'' 87(1):67-71, 2007. PMID 16997585 </ref>
*[[MDMA]] (ecstasy) may increase feelings of love, empathy and connection to others by stimulating oxytocin activity via activation of [[serotonin]] [[5-HT1A receptor]]s, if initial studies in animals apply to humans.<ref>Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS. A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy"). ''Neuroscience.'' 146:509-14, 2007. PMID 17383105</ref>
==Drug forms==
Synthetic oxytocin is sold as [[medication]] under the trade names '''Pitocin''' and '''Syntocinon''' and also as [[generic drug|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 [[Intravenous therapy|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 CNS entry of oxytocin by nasal spray. Oxytocin nasal sprays have been used to stimulate breastfeeding but the efficacy of this approach is doubtful<ref>Fewtrell MS, Loh KL, Blake A, Ridout DA, Hawdon J. Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants. Arch Dis Child Fetal Neonatal Ed. 2006 May;91(3):F169-74. PMID 16223754</ref>.
Injected oxytocin analogues are used to induce labor and support labor in case of non-progression of parturition. It has largely replaced [[ergotamine]] as the principal agent to increase uterine tone in acute [[postpartum haemorrhage]]. Oxytocin is also used in [[veterinary medicine]] to facilitate birth and to increase milk production. The [[tocolytic]] agent [[atosiban]] ('''Tractocile''') acts as an [[receptor antagonist|antagonist]] of oxytocin receptors; this drug is registered in many countries to suppress premature labour 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 anxiety|social anxieties]] and [[mood disorders]],<ref name="Petrovic"/> while others have noted the potential for abuse with [[confidence trick]]s. <ref>Boston Globe, January 12, 2006 [http://www.smh.com.au/news/mind-matters/to-sniff-at-danger/2006/01/12/1136956247384.html]</ref>
The herb [[fenugreek]] is used in animal husbandry and by breastfeeding mothers for its ability to increase oxytocin levels.
===Potential adverse reactions===
Oxytocin is relatively safe when used at recommended doses. Potential [[adverse drug reaction|side effect]]s include:{{Fact|date=February 2007}}
*[[Central nervous system]]: [[Subarachnoid hemorrhage]], [[seizure]]s.
*[[Cardiovascular system|Cardiovascular]]: [[Tachycardia|Increased heart rate]], decreased blood pressure, systemic venous return, [[cardiac output]], and [[cardiac arrhythmia|arrhythmia]]s.
*[[Genitourinary]]: Impaired uterine blood flow, pelvic hematoma, tetanic uterine contractions, uterine rupture, postpartum hemorrhage.
==Evolution==
Virtually all [[vertebrate]]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 always located close to each other (less than 15,000 bases apart) on the same [[chromosome]] and are transcribed in opposite 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 [[cyclostome]]s (modern members of the [[Agnatha]]).<ref name="Gimpl" />
==References==
{{Reflist|2}}
==External links==
* [http://www.newscientist.com/channel/being-human/mg19826561.900-cuddle-chemical-could-treat-mental-illness.html New Scientist] -'Cuddle chemical' could treat mental illness (14 May 2008)
*Caldwell, H.K. and Young, W.S., III. Oxytocin and Vasopressin: Genetics and Behavioral Implications in Lim, R. (ed.) Handbook of Neurochemistry and Molecular Neurobiology, 3rd edition, Springer, New York, pp. 573-607, 2006. [http://refworks.springer.com/mrw/fileadmin/pdf/Neurochemistry/0387303480C25.PDF 320kb PDF]
* [http://www.newscientist.com/channel/sex/mg18925365.500 NewScientist.com] - 'Release of Oxytocin due to penetrative sex reduces stress and neurotic tendencies', ''New Scientist'' (January 26, 2006)
* [http://www.oxytocin.org/oxytoc/love-science.html 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)
* [http://smh.com.au/news/mind-matters/to-sniff-at-danger/2006/01/12/1136956247384.html SMH.com.au] - 'To sniff at danger: Inhalable oxytocin could become a cure for social fears', ''[[Boston Globe]]'' (January 12, 2006)
* [http://kuchinskas.typepad.com/hug_the_monkey/ Hug the Monkey] - A weblog devoted entirely to oxytocin
* [http://psychcentral.com/news/2008/05/23/biochemical-effects-of-betrayal/2347.html PsychCentral.com] - Biochemical effects of betrayal (May 23, 2008)
* [http://www.rkliedtke.de/oxytocin2_us.html A Neurophysiologic Model of the Circuitry of Oxytocin in Arousal, Female Distress and Depression - Rainer K. Liedtke, MD]
{{Hormones}}
[[Category:Neuroscience]]
[[Category:Neurotransmitters]]
[[Category:Neuropeptides]]
[[Category:Posterior pituitary hormones]]
[[Category:Interpersonal chemistry]]
[[Category:Orgasm]]
[[Category:Breastfeeding]]
[[ar:أوكسيتوسين]]
[[be-x-old:Аксытацын]]
[[bs:Oksitocin]]
[[bg:Окситоцин]]
[[ca:Oxitocina]]
[[cs:Oxytocin]]
[[da:Oxytocin]]
[[de:Oxytocin]]
[[dv:އޮކްސިޓޯސިން]]
[[es:Oxitocina]]
[[fr:Ocytocine]]
[[hr:Oksitocin]]
[[id:Oksitosin]]
[[is:Oxytósín]]
[[it:Ossitocina]]
[[he:אוקסיטוצין]]
[[lt:Oksitocinas]]
[[hu:Oxitocin]]
[[mk:Окситоцин]]
[[nl:Oxytocine]]
[[ja:オキシトシン]]
[[no:Oksytocin]]
[[pl:Oksytocyna]]
[[pt:Ocitocina]]
[[ru:Окситоцин]]
[[sq:Oksitocina]]
[[sk:Oxytocín]]
[[sr:Окситоцин]]
[[fi:Oksitosiini]]
[[sv:Oxytocin]]
[[uk:Окситоцин]]
[[zh:催生素]]