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Gene Review

Oxt  -  oxytocin

Mus musculus

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

  • Having observed elevated OT levels in the fetal and newborn heart at a stage of intense cardiomyocyte hyperplasia, we hypothesized a role for OT in cardiomyocyte differentiation [1].
  • Oxytocin inhibits the progression of human ovarian carcinoma cells in vitro and in vivo [2].
  • OBJECTIVES: The objective of this study was to examine the effects of OT on both behavioral and autonomic parameters of the anxiety response in male mice using three pharmacologically validated preclinical models of anxiety: the four-plate test (FPT), elevated zero maze (EZM), and stress-induced hyperthermia (SIH) [3].
  • Continuous infusion of OT revealed that OT can either delay labor at low doses or initiate preterm labor at high doses [4].
  • Results show that OTKO -/- mice are characterized by 1) hypotension, suggesting that OT is involved in tonic BP maintenance; 2) enhanced baroreflex gain over a small BP range, suggesting that OT extends the functional range of arterial baroreceptor reflex; and 3) shift in autonomic balance, indicating that OT reduces the sympathetic reserve [5].
  • Our results support the importance of Oxt neurons in feeding regulation and suggest that reduced Oxt neuropeptide is one mechanism mediating the hyperphagic obesity of Sim1(+/-) mice [6].

Psychiatry related information on Oxt


High impact information on Oxt


Chemical compound and disease context of Oxt


Biological context of Oxt


Anatomical context of Oxt

  • We thus propose here a four-gene micronet, which links hypothalamic and limbic forebrain neurons in the estrogen control over the OT regulation of social recognition [24].
  • In the female rat, oestrogen receptor (ER) beta is colocalized with both oxytocin- and vasopressin-producing neurones in the paraventricular nucleus of the hypothalamus (PVN) [25].
  • The intracerebroventricular administration of OT, but not vehicle, artificial cerebrospinal fluid (aCSF), produced a robust increase in grooming behavior in both OT null and wild type animals, P<.001 [26].
  • Western blot analysis revealed a 48 kDa V1a and a 55 kDa OXT receptor immunoreactive band that was expressed in tissue obtained from L1-L6 sections of spinal cord [27].
  • With the use of an en bloc in vitro preparation of mouse spinal cord (2-3 d old), which either was isolated completely or had muscles of the hindlimb left intact, we show that the bath application of AVP or OXT can evoke an increase in population bursting of motoneurons recorded from the lumbar ventral roots [27].

Associations of Oxt with chemical compounds

  • Thus, we compared the effect of ovarian hormones on oxytocin and vasopressin mRNA expression in the PVN of wild-type (WT) and ERbeta knockout (betaERKO) mice [25].
  • In addition, reelin is critical to the development of the GABAergic system and GABA modulates the release of OT [28].
  • Collectively, these data point to a novel role for AVP and OXT in the activation of spinal motor networks [27].
  • In contrast, simultaneous oxytocin and COX-1 deficiency restored the normal onset of labor by allowing luteolysis in the absence of elevated PGF2alpha production [29].
  • In this work, P19 cells were allowed to aggregate from day 0 to day 4 in the presence of 0.5% DMSO, 10(-7) M OT and/or 10(-7) M OT antagonist (OTA), and then cultured in the absence of these factors until day 14 [1].

Physical interactions of Oxt

  • OT receptor distribution and binding in brains of OT null and wild type mice were examined by autoradiography and were not significantly different [26].

Co-localisations of Oxt

  • Neuronal NOS was exclusively colocalized with OT in the PVN and the SON, suggesting that NO is mainly synthesized by oxytocinergic neurons in mice [30].
  • We reported previously that leptin was co-localized with oxytocin and vasopressin [31].

Regulatory relationships of Oxt


Other interactions of Oxt

  • These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior [37].
  • An estrogen-dependent four-gene micronet regulating social recognition: a study with oxytocin and estrogen receptor-alpha and -beta knockout mice [24].
  • These results suggest that ERbeta is necessary for the regulation of the expression of oxytocin in the PVN [25].
  • Experimental evidence suggests that AVP improves, and OT impairs, learning and memory [8].
  • In addition, when we applied AVP or OXT in combination with a 5-HT2 agonist, bouts of locomotor-like activity could be observed in a majority of preparations [27].

Analytical, diagnostic and therapeutic context of Oxt


  1. Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes. Paquin, J., Danalache, B.A., Jankowski, M., McCann, S.M., Gutkowska, J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Oxytocin inhibits the progression of human ovarian carcinoma cells in vitro and in vivo. Morita, T., Shibata, K., Kikkawa, F., Kajiyama, H., Ino, K., Mizutani, S. Int. J. Cancer (2004) [Pubmed]
  3. Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications. Ring, R.H., Malberg, J.E., Potestio, L., Ping, J., Boikess, S., Luo, B., Schechter, L.E., Rizzo, S., Rahman, Z., Rosenzweig-Lipson, S. Psychopharmacology (Berl.) (2006) [Pubmed]
  4. Oxytocin modulates the onset of murine parturition by competing ovarian and uterine effects. Imamura, T., Luedke, C.E., Vogt, S.K., Muglia, L.J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2000) [Pubmed]
  5. Oxytocinergic regulation of cardiovascular function: studies in oxytocin-deficient mice. Michelini, L.C., Marcelo, M.C., Amico, J., Morris, M. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  6. Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice. Kublaoui, B.M., Gemelli, T., Tolson, K.P., Wang, Y., Zinn, A.R. Mol. Endocrinol. (2008) [Pubmed]
  7. Estrogen modulates oxytocin gene expression in regions of the rat supraoptic and paraventricular nuclei that contain estrogen receptor-beta. Shughrue, P.J., Dellovade, T.L., Merchenthaler, I. Prog. Brain Res. (2002) [Pubmed]
  8. Effects of a single administration of oxytocin or vasopressin and their interactions with two selective receptor antagonists on memory storage in mice. Boccia, M.M., Kopf, S.R., Baratti, C.M. Neurobiology of learning and memory. (1998) [Pubmed]
  9. Involvement of estrogen receptor alpha, beta and oxytocin in social discrimination: a detailed behavioral analysis with knockout female mice. Choleris, E., Ogawa, S., Kavaliers, M., Gustafsson, J.A., Korach, K.S., Muglia, L.J., Pfaff, D.W. Genes Brain Behav. (2006) [Pubmed]
  10. Corticosterone release is heightened in food or water deprived oxytocin deficient male mice. Mantella, R.C., Vollmer, R.R., Amico, J.A. Brain Res. (2005) [Pubmed]
  11. Social amnesia in mice lacking the oxytocin gene. Ferguson, J.N., Young, L.J., Hearn, E.F., Matzuk, M.M., Insel, T.R., Winslow, J.T. Nat. Genet. (2000) [Pubmed]
  12. Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. Ossowski, L., Biegel, D., Reich, E. Cell (1979) [Pubmed]
  13. Regulation of maternal behavior and offspring growth by paternally expressed Peg3. Li, L., Keverne, E.B., Aparicio, S.A., Ishino, F., Barton, S.C., Surani, M.A. Science (1999) [Pubmed]
  14. New roles for estrogen receptor beta in behavior and neuroendocrinology. Bodo, C., Rissman, E.F. Frontiers in neuroendocrinology. (2006) [Pubmed]
  15. Anxiety and stress responses in female oxytocin deficient mice. Amico, J.A., Mantella, R.C., Vollmer, R.R., Li, X. J. Neuroendocrinol. (2004) [Pubmed]
  16. An anxiolytic action of oxytocin is enhanced by estrogen in the mouse. McCarthy, M.M., McDonald, C.H., Brooks, P.J., Goldman, D. Physiol. Behav. (1996) [Pubmed]
  17. The role of oxytocin-dopamine interactions in cocaine-induced locomotor hyperactivity. Kovàcs, G.L., Sarnyai, Z., Barbarczi, E., Szabó, G., Telegdy, G. Neuropharmacology (1990) [Pubmed]
  18. On the mode of action of an oxytocin derivative (Z-Pro-D-Leu) on morphine-dependence in mice. Kovács, G.L., Szontágh, L., Baláspiri, L., Hódi, K., Bohus, P., Telegdy, G. Neuropharmacology (1981) [Pubmed]
  19. Social and sexual motivation in the mouse. Matthews, T.J., Abdelbaky, P., Pfaff, D.W. Behav. Neurosci. (2005) [Pubmed]
  20. The pituitary hormones arginine vasopressin-neurophysin II and oxytocin-neurophysin I show close linkage with interleukin-1 on mouse chromosome 2. Marini, J.C., Nelson, K.K., Battey, J., Siracusa, L.D. Genomics (1993) [Pubmed]
  21. Selective activation of the hypothalamic vasopressinergic system in mice deficient for the corticotropin-releasing hormone receptor 1 is dependent on glucocorticoids. Müller, M.B., Landgraf, R., Preil, J., Sillaber, I., Kresse, A.E., Keck, M.E., Zimmermann, S., Holsboer, F., Wurst, W. Endocrinology (2000) [Pubmed]
  22. Localization and characterization of binding sites for vasopressin and oxytocin in the brain of the guinea pig. Tribollet, E., Barberis, C., Dubois-Dauphin, M., Dreifuss, J.J. Brain Res. (1992) [Pubmed]
  23. Oxytocin and estrogen receptor expression in the myometrium of pregnant relaxin-deficient (Rlx-/-) mice. Siebel, A.L., Gehring, H.M., Vodstrcil, L., Parry, L.J. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  24. An estrogen-dependent four-gene micronet regulating social recognition: a study with oxytocin and estrogen receptor-alpha and -beta knockout mice. Choleris, E., Gustafsson, J.A., Korach, K.S., Muglia, L.J., Pfaff, D.W., Ogawa, S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  25. Oxytocin, but not oxytocin receptor, is rRegulated by oestrogen receptor beta in the female mouse hypothalamus. Patisaul, H.B., Scordalakes, E.M., Young, L.J., Rissman, E.F. J. Neuroendocrinol. (2003) [Pubmed]
  26. Centrally administered oxytocin elicits exaggerated grooming in oxytocin null mice. Amico, J.A., Vollmer, R.R., Karam, J.R., Lee, P.R., Li, X., Koenig, J.I., McCarthy, M.M. Pharmacol. Biochem. Behav. (2004) [Pubmed]
  27. Peptidergic activation of locomotor pattern generators in the neonatal spinal cord. Pearson, S.A., Mouihate, A., Pittman, Q.J., Whelan, P.J. J. Neurosci. (2003) [Pubmed]
  28. Oxytocin receptors in brain cortical regions are reduced in haploinsufficient (+/-) reeler mice. Liu, W., Pappas, G.D., Carter, C.S. Neurol. Res. (2005) [Pubmed]
  29. Opposing actions of prostaglandins and oxytocin determine the onset of murine labor. Gross, G.A., Imamura, T., Luedke, C., Vogt, S.K., Olson, L.M., Nelson, D.M., Sadovsky, Y., Muglia, L.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  30. The effects of nitric oxide on magnocellular neurons could involve multiple indirect cyclic GMP-dependent pathways. Vacher, C.M., Hardin-Pouzet, H., Steinbusch, H.W., Calas, A., De Vente, J. Eur. J. Neurosci. (2003) [Pubmed]
  31. Hypothalamic resistin immunoreactivity is reduced by obesity in the mouse: co-localization with alpha-melanostimulating hormone. Wilkinson, M., Wilkinson, D., Wiesner, G., Morash, B., Ur, E. Neuroendocrinology (2005) [Pubmed]
  32. Enhanced up-regulation of corticotropin-releasing hormone gene expression in response to restraint stress in the hypothalamic paraventricular nucleus of oxytocin gene-deficient male mice. Nomura, M., Saito, J., Ueta, Y., Muglia, L.J., Pfaff, D.W., Ogawa, S. J. Neuroendocrinol. (2003) [Pubmed]
  33. Nuclear orphan receptors COUP-TFII and Ear-2: presence in oxytocin-producing uterine cells and functional interaction with the oxytocin gene promoter. Chu, K., Boutin, J.M., Breton, C., Zingg, H.H. Mol. Cell. Endocrinol. (1998) [Pubmed]
  34. Dehydration anorexia is attenuated in oxytocin-deficient mice. Rinaman, L., Vollmer, R.R., Karam, J., Phillips, D., Li, X., Amico, J.A. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  35. Cholecystokinin and D-fenfluramine inhibit food intake in oxytocin-deficient mice. Mantella, R.C., Rinaman, L., Vollmer, R.R., Amico, J.A. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  36. The effect of Ca deprivation and of Ca-blocking drugs on oxytocin-induced contractions of the male mouse anococcygeus. Gibson, A., Shaw, C.R. J. Pharm. Pharmacol. (1989) [Pubmed]
  37. Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Takayanagi, Y., Yoshida, M., Bielsky, I.F., Ross, H.E., Kawamata, M., Onaka, T., Yanagisawa, T., Kimura, T., Matzuk, M.M., Young, L.J., Nishimori, K. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  38. Vasopressin stimulates insulin release from islet cells through V1b receptors: a combined pharmacological/knockout approach. Oshikawa, S., Tanoue, A., Koshimizu, T.A., Kitagawa, Y., Tsujimoto, G. Mol. Pharmacol. (2004) [Pubmed]
  39. Endocrinomic profile of neurointermediate lobe pituitary prohormone processing in PC1/3- and PC2-Null mice using SELDI-TOF mass spectrometry. Hardiman, A., Friedman, T.C., Grunwald, W.C., Furuta, M., Zhu, Z., Steiner, D.F., Cool, D.R. J. Mol. Endocrinol. (2005) [Pubmed]
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