Wikia

Psychology Wiki

Oxytocin

Talk1
34,138pages on
this wiki
Revision as of 15:33, December 7, 2013 by Dr Joe Kiff (Talk | contribs)

(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)

Assessment | Biopsychology | Comparative | Cognitive | Developmental | Language | Individual differences | Personality | Philosophy | Social |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |

Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)


This is a background article. See Psychological correlates of oxytocin

Oxytocin chemical structure
Oxytocin

1-({(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-(4-hydroxybenzyl)-13-[(1S)-1-methylpropyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl}carbonyl)-L-prolyl-L-leucylglycinamide
IUPAC name
CAS number
50-56-6
ATC code

H01BB02

PubChem
439302
DrugBank
DB00107
Chemical formula {{{chemical_formula}}}
Molecular weight 1007.19 g/mol
Bioavailability nil
Metabolism hepatic oxytocinases
Elimination half-life 1–6 min
Excretion Biliary and renal
Pregnancy category {{{pregnancy_category}}}
Legal status {{{legal_status}}}
Routes of administration Intranasal, IV, IM


Oxytocin (Oxt) (11px /ˌɒksɨˈtsɪn/) is a mammalian 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 nipples, facilitating breastfeeding.

Recent studies have begun to investigate oxytocin's role in various behaviors, including orgasm, social recognition, pair bonding, anxiety, and maternal behaviors.[1] 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.[2]

The word oxytocin was coined from the Greek ὼκυτοκίνη, ōkytokínē, meaning “quick birth”, after its uterine-contracting properties were discovered by Dale in 1906.[3] The milk ejection property of Oxt was described by Ott and Scott in 1910[4] and by Schafer and Mackenzie in 1911.[5] The nine amino acid sequence of Oxt was elucidated by Vincent du Vigneaud et al. and by Tuppy in 1953.[6] and synthesized biochemically soon after by du Vigneaud et al. in 1953.[7][8] Oxytocin was the very first polypeptide hormone to be sequenced and synthesized.

Structure and relation to vasopressinEdit

Oxytocin is a peptide of nine amino acids (a nonapeptide). Its systematic name is cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amine (cystyrileglnasncysproleugly - 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 micrograms 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.[9] 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.[10]

File:Oxytocin-neurophysin.png

The structure of oxytocin is very similar to that of vasopressin (cystyrpheglnasncysproarggly - 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.


ActionsEdit

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 that requires Mg2+ and cholesterol. It belongs to the rhodopsin-type (class I) group of G-protein-coupled receptors.

Physiological effectsEdit

The peripheral actions of oxytocin mainly reflect secretion from the pituitary gland. (See oxytocin receptor for more detail on its action.)

  • Letdown reflex – in lactating (breastfeeding) mothers, oxytocin acts at the mammary glands, causing milk to be 'let down' into subareolar sinuses, from where it can be excreted via the nipple.[11] 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. 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 mice lacking the oxytocin receptor, reproductive behavior and parturition are normal.[12]
  • Due to its similarity to vasopressin, it can reduce the excretion of urine slightly. 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.[13][14] However, the absence of either oxytocin or its receptor in knockout mice has not been reported to produce cardiac insufficiencies.[12]

Psychological effectsEdit

Main article: Psychological correlates of oxytocin

Drug formsEdit

Synthetic oxytocin is sold as proprietary medication 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.[16]

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).

UsesEdit

Treatment for social anxietyEdit

Some have suggested that the trust-inducing property of oxytocin might help those who suffer from social anxieties and mood disorders,[17] while others have noted the potential for abuse with confidence tricks[18][19] and military applications.[20]

Treatment in autismEdit

Main article: Oxytocin treatment for autism

The Center of Cognitive Neuroscience in Lyon, France concluded that oxytocin may help reduce the negative symptoms of autism.[21]

Treatment for postpartum depressionEdit

Main article: Oxytocin treatment for postpartum depression

Potential adverse reactionsEdit

Oxytocin is relatively safe when used at recommended doses, and side-effects are uncommon.[22] The following maternal events have been reported:[22]

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:[22]

In addition, use of pitocin in the mother has been associated with neonatal jaundice, retinal hemorrhage, and low five-minute Apgar score.

Industrial useEdit

Oxytocin can be administered to bovine animals in order to increase the production of dairy milk.[citation needed]

Synthesis, storage, and releaseEdit

edit
Template:PBB/5020


The oxytocin peptide is synthesized as an inactive precursor protein from the OXT gene.[23][24][25] This precursor protein also includes the oxytocin carrier protein neurophysin I.[26] 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).[27]

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.[28] 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.[29]

Neural sourcesEdit

In the hypothalamus, oxytocin is made in magnocellular neurosecretory cells 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.[30] The peripheral hormonal and behavioral brain effects of oxytocin it has been suggested are coordinated through its common release through these collaterals.[30] Oxytocin is also made by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord.[31] 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 potentials that propagate down axons 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.

Non-neural sourcesEdit

Outside the brain, oxytocin-containing cells have been identified in several diverse tissues including the corpus luteum,[32][33] the interstitial cells of Leydig,[34] the retina,[35] the adrenal medulla,[36] the placenta,[37] the thymus[38] and the pancreas.[39] 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.

FemaleEdit

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 F to cause regression of the corpus luteum.

MaleEdit

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 C endogenously), and in guinea pigs, which, like humans, require an exogenous source of vitamin C (ascorbate) in their diets.[40]

Genetics of oxytocinEdit

Oxytocin receptor polymorphismEdit

The oxytocin receptor in humans has several alleles, 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,[41] as well as lower prevalence of autism and of poor parenting skills.[42]

EvolutionEdit

Virtually all vertebrates 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,[43] 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).[44]

See alsoEdit

ReferencesEdit

  1. Lee HJ, Macbeth AH, Pagani JH, Young WS (June 2009). Oxytocin: the Great Facilitator of Life. Progress in Neurobiology 88 (2): 127–51.
  2. includeonly>O'Callaghan, Tiffany. "Thanks, Mom!", Time Magazine, Time, Inc., 7, June 2010. Retrieved on 2010-06-08.
  3. Dale HH (May 1906). On some physiological actions of ergot. J. Physiol. (Lond.) 34 (3): 163–206.
  4. Ott I, Scott JC. The Action of Infundibulum upon Mammary Secretion. Proc Soc Exp Biol. (1910) p.8:48–49.
  5. Schafer EA, Mackenzie K. The action of animal extracts on milk secretion. Proceedings of the Royal Society of London Series B-Containing Papers of a Biological Character. (1911) p.84:16–22.
  6. du Vigneaud V, Ressler C, Trippett S (December 1953). The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. J. Biol. Chem. 205 (2): 949–57.
  7. du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG, Gordon S (1953). The synthesis of an octapeptide amide with the hormonal activity of oxytocin. J. Am. Chem. Soc. 75 (19): 4879–80.
  8. du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG (June 1954). The synthesis of oxytocin. J. Am. Chem. Soc. 76 (12): 3115–3121.
  9. du Vigneaud V. (1960). Experiences in the Polypeptide Field: Insulin to Oxytocin. Ann. NY Acad. Sci. 88 (3): 537–48.
  10. Kukucka, Mark A. Mechanisms by which hypoxia augments Leydig cell viability and differentiated cell function in vitro. Digital Library and Archives. URL accessed on 2010-02-21.
  11. http://emedicine.medscape.com/article/976504-overview
  12. 12.0 12.1 Takayanagi Y (November 2005). Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proceedings of the National Academy of Sciences of the United States of America 102 (44): 16096–101.
  13. Paquin J, Danalache BA, Jankowski M, McCann SM, Gutkowska J (July 2002). Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes. Proceedings of the National Academy of Sciences of the United States of America 99 (14): 9550–5.
  14. Jankowski M (August 2004). Oxytocin in cardiac ontogeny. Proceedings of the National Academy of Sciences of the United States of America 101 (35): 13074–9.
  15. Hartwig, Walenty (1989). Endokrynologia praktyczna, Warsaw: Państwowy Zakład Wydawnictw Lekarskich.Template:Page needed
  16. Fewtrell MS, Loh KL, Blake A, Ridout DA, Hawdon J (May 2006). Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 91 (3): F169–74.
  17. Cite error: Invalid <ref> tag; no text was provided for refs named pmid20371820
  18. Petrovic P, Kalisch R, Singer T, Dolan RJ (June 2008). Oxytocin Attenuates Affective Evaluations of Conditioned Faces and Amygdala Activity. The Journal of Neuroscience 28 (26): 6607–15.
  19. includeonly>"To sniff at danger - Mind Matters", Health And Fitness, Boston Globe, 2006-01-12. Retrieved on 2009-04-13.
  20. Dando M (August 2009). Biologists napping while work militarized. Nature 460 (7258): 950–1.
  21. includeonly>""Love" hormone may help autism symptoms", Reuters, 2010-02-17.
  22. 22.0 22.1 22.2 Pitocin (drug label for professionals). Rx List. WebMD. URL accessed on 2010-09-09.
  23. Sausville E, Carney D, Battey J (August 1985). The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line. J. Biol. Chem. 260 (18): 10236–41.
  24. Repaske DR, Phillips JA, Kirby LT, Tze WJ, D'Ercole AJ, Battey J (March 1990). Molecular analysis of autosomal dominant neurohypophyseal diabetes insipidus. J. Clin. Endocrinol. Metab. 70 (3): 752–7.
  25. Summar ML, Phillips JA, Battey J, Castiglione CM, Kidd KK, Maness KJ, Weiffenbach B, Gravius TC (June 1990). Linkage relationships of human arginine vasopressin-neurophysin-II and oxytocin-neurophysin-I to prodynorphin and other loci on chromosome 20. Mol. Endocrinol. 4 (6): 947–50.
  26. Brownstein MJ, Russell JT, Gainer H (January 1980). Synthesis, transport, and release of posterior pituitary hormones. Science 207 (4429): 373–8.
  27. Sheldrick EL, Flint AP (July 1989). Post-translational processing of oxytocin-neurophysin prohormone in the ovine corpus luteum: activity of peptidyl glycine alpha-amidating mono-oxygenase and concentrations of its cofactor, ascorbic acid. J. Endocrinol. 122 (1): 313–22.
  28. Luck MR, Jungclas B (September 1987). Catecholamines and ascorbic acid as stimulators of bovine ovarian oxytocin secretion. J. Endocrinol. 114 (3): 423–30.
  29. Hornig D (September 1975). Distribution of ascorbic acid, metabolites and analogues in man and animals. Ann. N. Y. Acad. Sci. 258: 103–18.
  30. 30.0 30.1 Ross HE (September 2009). Characterization of the Oxytocin System Regulating Affiliative Behavior in Female Prairie Voles. Neuroscience 162 (4): 892–903.
  31. Landgraf R, Neumann ID (2004). Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Frontiers in Neuroendocrinology 25 (3–4): 150–76.
  32. Wathes DC, Swann RW (May 1982). Is oxytocin an ovarian hormone?. Nature 297 (5863): 225–7.
  33. Wathes DC, Swann RW, Pickering BT, Porter DG, Hull MG, Drife JO (August 1982). Neurohypophysial hormones in the human ovary. Lancet 2 (8295): 410–2.
  34. Guldenaar SE, Pickering BT (1985). Immunocytochemical evidence for the presence of oxytocin in rat testis. Cell Tissue Res. 240 (2): 485–7.
  35. Gauquelin G, Geelen G, Louis F, Allevard AM, Meunier C, Cuisinaud G, Benjanet S, Seidah NG, Chretien M, Legros JJ (1983). Presence of vasopressin, oxytocin and neurophysin in the retina of mammals, effect of light and darkness, comparison with the neuropeptide content of the neurohypophysis and the pineal gland. Peptides 4 (4): 509–15.
  36. Ang VT, Jenkins JS (April 1984). Neurohypophysial hormones in the adrenal medulla. J. Clin. Endocrinol. Metab. 58 (4): 688–91.
  37. Fields PA, Eldridge RK, Fuchs AR, Roberts RF, Fields MJ (April 1983). Human placental and bovine corpora luteal oxytocin. Endocrinology 112 (4): 1544–6.
  38. Geenen V, Legros JJ, Franchimont P, Baudrihaye M, Defresne MP, Boniver J (April 1986). The neuroendocrine thymus: coexistence of oxytocin and neurophysin in the human thymus. Science 232 (4749): 508–11.
  39. Amico JA, Finn FM, Haldar J (November 1988). Oxytocin and vasopressin are present in human and rat pancreas. Am. J. Med. Sci. 296 (5): 303–7.
  40. Kukucka Mark A, Misra Hara P (1992). HPLC determination of an oxytocin-like peptide produced by isolated guinea pig Leydig cells: stimulation by ascorbate. Arch. Androl. 29 (2): 185–90.
  41. Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D (December 2009). Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proceedings of the National Academy of Sciences of the United States of America 106 (50): 21437–41.
  42. includeonly>Angier, Natalie. "The Biology Behind the Milk of Human Kindness", The New York Times, 2009-11-24.
  43. Venkatesh B, Si-Hoe SL, Murphy D, Brenner S (November 1997). Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes. Proceedings of the National Academy of Sciences of the United States of America 94 (23): 12462–6.
  44. Cite error: Invalid <ref> tag; no text was provided for refs named Gimpl

Further readingEdit

  • Lee HJ, Macbeth AH, Pagani JH, Young WS (June 2009). Oxytocin: the Great Facilitator of Life. Progress in Neurobiology 88 (2): 127–51.
  • Caldwell HK, Young WS III (2006). "Oxytocin and Vasopressin: Genetics and Behavioral Implications" Abel L, Lim R Handbook of neurochemistry and molecular neurobiology, 573–607, Berlin: Springer.


External linksEdit


|}

Target-derived NGF, BDNF, NT-3

|}


|}

|}


This page uses Creative Commons Licensed content from Wikipedia (view authors).

Around Wikia's network

Random Wiki