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Gene Review

OXT  -  oxytocin/neurophysin I prepropeptide

Homo sapiens

Synonyms: OT, OT-NPI, OXT-NPI, Oxytocin-neurophysin 1
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Disease relevance of OXT


Psychiatry related information on OXT


High impact information on OXT

  • However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart [9].
  • While the essential role of OT for the milk let-down reflex has been confirmed in OT-deficient mice, OT's role in parturition is obviously more complex [9].
  • The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei [9].
  • Thus, to initiate labor, it might be essential to generate sufficient PGF(2 alpha) to overcome the luteotrophic action of OT in late gestation [9].
  • The function and physiological regulation of the OT system is strongly steroid dependent [9].

Chemical compound and disease context of OXT

  • OXT inhibited cocaine-induced exploratory activity, locomotor hyperactivity, and stereotyped behavior in rats and in mice [8].
  • In hyperprolactinaemic females (22-41 y, n=6, three with pituitary adenomas), water retention was registered following an OWL, together with paradoxical AVP and OXT level increases, whereas the cortisol response remained normal, and the PRL level did not change at all [10].
  • Furthermore, two proteins with apparent molecular masses of 125 and 60 kDa became tyrosine phosphorylated in all of the cell lines after OT stimulation (and an additional protein of 45 kDa in BeWo choriocarcinoma cells), suggesting that this peptide can stimulate tyrosine kinase activity [11].
  • In fact, we found that in a rabbit model of hypogonadotropic hypogonadism (induced by a single administration of the long-acting GnRH agonist triptorelin pamoate, 2.9 mg/kg), OT responsiveness was strongly reduced and was completely restored by estradiol valerate (3.3 mg/kg weekly), but not by testosterone enanthate (30 mg/kg weekly) [12].
  • CSF AVP levels were significantly elevated in benign intracranial hypertension (2.1, SE 0.3 pmol/l) compared with controls (0.7, SE 0.1 pmol/l, p less than 0.001) but CSF OT concentrations were similar in both groups [13].

Biological context of OXT


Anatomical context of OXT


Associations of OXT with chemical compounds

  • We conclude that a significant increase in both OT and E2 occurs at the myometrial decidual interface with labor, and this increase is reflected in both the fundal and lower segments of the uterus [17].
  • Serum/DEX up-regulation of OTR restored the responsiveness to OT [2].
  • Furthermore, OT increased EGFR tyrosine phosphorylation in OTR-COSM6 cells, which was inhibited by AG1478 or EGTA plus thapsigargin pretreatment [3].
  • Alanine substitution for H7.62 or Q7.66 did not substantially affect the affinity for OT (K(d) = 0.63 and 0.48 nM, respectively, vs 0.52 nM for the wild type), whereas substitution for H7.59, E7.63, or R7.67 reduced the affinity 5-6-fold [19].
  • The variable receptor content may indicate the differential responsiveness to estrogen in distinct OT and VP neuronal populations [20].

Physical interactions of OXT

  • Chimeric vasopressin V2/OT receptors were constructed and investigated to identify receptor regions involved in ligand binding or G protein coupling [21].
  • Molecular simulations of the free and OT-bound forms of wild-type OTR and of the D136(3.49)N constitutively active mutant suggest that the receptor portions close to the E/DRY and NPxxY motifs are particularly susceptible to undergoing structural modification in response to activating mutations and agonist binding [22].
  • The results of this study suggest that serotonergic 5HT1A receptors may interact with hypoglycemia in the stimulation of OT, but not AVP secretion [23].

Regulatory relationships of OXT

  • We hypothesized that activation of PKC mediated this OT-induced decrease in OTR expression [24].
  • Conclusions: These findings suggested that P-LAP on the plasma membrane in HUVECs regulates the effects of OT with resolution around OTR [25].
  • Second, the human and bovine OT promoter can be made artificially responsive towards oestrogen in a cotransfection system over-expressing ERalpha or ERbeta, but not in cells expressing natural levels of these steroid receptors [26].
  • The administration of OT (2 IU as a i.v. bolus plus 4 IU infused in 2 h) significantly reduced the metyrapone-induced plasma ACTH rise [27].
  • For AVP there was lack of such correlation which may suggest that this hormone influences both the OT and AVP V1a receptor sites [28].

Other interactions of OXT

  • [3H]Thymidine incorporations, applied on H345 cells, demonstrated a dose-dependent mitogenic effect of exogenous OT (1 and 100 nM) that was abolished by the OTR antagonist OVTA [14].
  • Thus, agonist stimulation of AVP/OT receptors leads to receptor subtype-specific interactions with GRK and PKC through specific motifs present in the C termini of the receptors [29].
  • These neuroanatomical studies provide detailed information about the topographical distribution and cellular abundance of ER-beta within subsets of hypothalamic OT and VP neurons in the rat [20].
  • Hypothalamic sections were stained for OT, VP, and CRH [30].
  • Attenuation of the OT response by the Gbetagamma scavenger carboxyl terminus of the beta-adrenergic receptor kinase implicated a Gbetagamma-mediated pathway [3].

Analytical, diagnostic and therapeutic context of OXT

  • HPLC purification and mass spectrometry analysis confirmed that immunoreactive OT corresponded to alpha-amidated OT [17].
  • RT-PCR and RIA demonstrated a labor-associated increase in OT mRNA and peptide in CD, AM, and FU, but not LS [17].
  • Northern blot analysis shows that the mRNAs for the two prepro-hormones consist of approximately 840 (AVP) and approximately 700 (OT) nucleotides [31].
  • Utilizing our established model for extracorporeal perfusion of the human uterus, we perfused 15 human uteri for 27 h under physiological conditions without oestradiol (group A, n = 5) or with high E(2) stimulation (group B, n = 5) followed by OT stimulation for both groups during the last 3 h of the experiment [32].
  • PCR amplifications were carried out using gene-specific OT and OT-receptor primers [33].


  1. The human gene for oxytocin-neurophysin I (OXT) is physically mapped to chromosome 20p13 by in situ hybridization. Rao, V.V., Löffler, C., Battey, J., Hansmann, I. Cytogenet. Cell Genet. (1992) [Pubmed]
  2. Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway. Copland, J.A., Jeng, Y.J., Strakova, Z., Ives, K.L., Hellmich, M.R., Soloff, M.S. Endocrinology (1999) [Pubmed]
  3. Extracellular signal-regulated kinase 1/2 activation by myometrial oxytocin receptor involves Galpha(q)Gbetagamma and epidermal growth factor receptor tyrosine kinase activation. Zhong, M., Yang, M., Sanborn, B.M. Endocrinology (2003) [Pubmed]
  4. Role of oxytocin in the ejaculatory process. Filippi, S., Vignozzi, L., Vannelli, G.B., Ledda, F., Forti, G., Maggi, M. J. Endocrinol. Invest. (2003) [Pubmed]
  5. Decreased number of oxytocin neurons in the paraventricular nucleus of the human hypothalamus in AIDS. Purba, J.S., Hofman, M.A., Portegies, P., Troost, D., Swaab, D.F. Brain (1993) [Pubmed]
  6. Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Purba, J.S., Hoogendijk, W.J., Hofman, M.A., Swaab, D.F. Arch. Gen. Psychiatry (1996) [Pubmed]
  7. Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases. Swaab, D.F., Purba, J.S., Hofman, M.A. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  8. Role of oxytocin in the neuroadaptation to drugs of abuse. Sarnyai, Z., Kovács, G.L. Psychoneuroendocrinology (1994) [Pubmed]
  9. The oxytocin receptor system: structure, function, and regulation. Gimpl, G., Fahrenholz, F. Physiol. Rev. (2001) [Pubmed]
  10. Neurohypophysial hormone secretion in hyperprolactinaemic women. Laczi, F., Szasz, A., Vecsernyes, M., Julesz, J. Neuropeptides (1998) [Pubmed]
  11. Activation of functional oxytocin receptors stimulates cell proliferation in human trophoblast and choriocarcinoma cell lines. Cassoni, P., Sapino, A., Munaron, L., Deaglio, S., Chini, B., Graziani, A., Ahmed, A., Bussolati, G. Endocrinology (2001) [Pubmed]
  12. Oxytocin receptor is expressed in the penis and mediates an estrogen-dependent smooth muscle contractility. Vignozzi, L., Filippi, S., Luconi, M., Morelli, A., Mancina, R., Marini, M., Vannelli, G.B., Granchi, S., Orlando, C., Gelmini, S., Ledda, F., Forti, G., Maggi, M. Endocrinology (2004) [Pubmed]
  13. Cerebrospinal fluid neurohypophysial peptides in benign intracranial hypertension. Seckl, J., Lightman, S. J. Neurol. Neurosurg. Psychiatr. (1988) [Pubmed]
  14. Oxytocin synthesis and oxytocin receptor expression by cell lines of human small cell carcinoma of the lung stimulate tumor growth through autocrine/paracrine signaling. Péqueux, C., Breton, C., Hendrick, J.C., Hagelstein, M.T., Martens, H., Winkler, R., Geenen, V., Legros, J.J. Cancer Res. (2002) [Pubmed]
  15. The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line. Sausville, E., Carney, D., Battey, J. J. Biol. Chem. (1985) [Pubmed]
  16. Oxytocin mediates the estrogen-dependent contractile activity of endothelin-1 in human and rabbit epididymis. Filippi, S., Morelli, A., Vignozzi, L., Vannelli, G.B., Marini, M., Ferruzzi, P., Mancina, R., Crescioli, C., Mondaini, N., Forti, G., Ledda, F., Maggi, M. Endocrinology (2005) [Pubmed]
  17. Paracrine oxytocin and estradiol demonstrate a spatial increase in human intrauterine tissues with labor. Blanks, A.M., Vatish, M., Allen, M.J., Ladds, G., de Wit, N.C., Slater, D.M., Thornton, S. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  18. Hypothalamic oxytocin: a cerebrovascular modulator in man? Abrams, G.M., Nilaver, G., Recht, L.R., Haldar, J., Zimmerman, E.A. Neurology (1985) [Pubmed]
  19. Residues in the hydrophilic face of putative helix 8 of oxytocin receptor are important for receptor function. Zhong, M., Navratil, A.M., Clay, C., Sanborn, B.M. Biochemistry (2004) [Pubmed]
  20. Estrogen receptor-beta in oxytocin and vasopressin neurons of the rat and human hypothalamus: Immunocytochemical and in situ hybridization studies. Hrabovszky, E., Kalló, I., Steinhauser, A., Merchenthaler, I., Coen, C.W., Petersen, S.L., Liposits, Z. J. Comp. Neurol. (2004) [Pubmed]
  21. Identification of neurohypophysial hormone receptor domains involved in ligand binding and G protein coupling. Postina, R., Kojro, E., Fahrenholz, F. Adv. Exp. Med. Biol. (1998) [Pubmed]
  22. The DRY motif as a molecular switch of the human oxytocin receptor. Favre, N., Fanelli, F., Missotten, M., Nichols, A., Wilson, J., di Tiani, M., Rommel, C., Scheer, A. Biochemistry (2005) [Pubmed]
  23. Different effects of the serotonergic agonists buspirone and sumatriptan on the posterior pituitary hormonal responses to hypoglycemia in humans. Chiodera, P., Volpi, R., Capretti, L., Caffarri, G., Magotti, M.G., Coiro, V. Neuropeptides (1996) [Pubmed]
  24. Phorbol ester treatment of human myometrial cells suppresses expression of oxytocin receptor through a mechanism that does not involve activator protein-1. Ball, A., Wang, J.W., Wong, S., Zielnik, B., Mitchell, J., Wang, N., Stemerman, M.B., Mitchell, B.F. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  25. Placental leucine aminopeptidase might regulate the effects of oxytocin with resolution in endothelial cells. Sano, M., Itakura, A., Ito, M., Takeuchi, M., Okada, M., Kotani, T., Mizutani, S., Kikkawa, F. Med. Sci. Monit. (2005) [Pubmed]
  26. The affinity and activity of the multiple hormone response element in the proximal promoter of the human oxytocin gene. Stedronsky, K., Telgmann, R., Tillmann, G., Walther, N., Ivell, R. J. Neuroendocrinol. (2002) [Pubmed]
  27. Oxytocin reduces metyrapone-induced ACTH secretion in human subjects. Chiodera, P., Coiro, V. Brain Res. (1987) [Pubmed]
  28. Potential use of oxytocin and vasopressin V1a antagonists in the treatment of preterm labour and primary dysmenorrhoea. Akerlund, M., Melin, P., Maggi, M. Adv. Exp. Med. Biol. (1995) [Pubmed]
  29. Dynamic interaction of human vasopressin/oxytocin receptor subtypes with G protein-coupled receptor kinases and protein kinase C after agonist stimulation. Berrada, K., Plesnicher, C.L., Luo, X., Thibonnier, M. J. Biol. Chem. (2000) [Pubmed]
  30. Effects of chronic alcoholic disease on magnocellular and parvocellular hypothalamic neurons in men. Sivukhina, E.V., Dolzhikov, A.A., Morozov, I.u.E., Jirikowski, G.F., Grinevich, V. Horm. Metab. Res. (2006) [Pubmed]
  31. Expression of the vasopressin and oxytocin genes in human hypothalami. Mohr, E., Hillers, M., Ivell, R., Haulica, I.D., Richter, D. FEBS Lett. (1985) [Pubmed]
  32. Oxytocin receptor gene expression of estrogen-stimulated human myometrium in extracorporeally perfused non-pregnant uteri. Richter, O.N., Kübler, K., Schmolling, J., Kupka, M., Reinsberg, J., Ulrich, U., van der Ven, H., Wardelmann, E., van der Ven, K. Mol. Hum. Reprod. (2004) [Pubmed]
  33. Oxytocin and oxytocin-receptor mRNA expression in the human gastrointestinal tract: a polymerase chain reaction study. Monstein, H.J., Grahn, N., Truedsson, M., Ohlsson, B. Regul. Pept. (2004) [Pubmed]
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