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Gene Review

Oxtr  -  oxytocin receptor

Mus musculus

Synonyms: OT-R, OTR, Oxytocin receptor
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Disease relevance of Oxtr


Psychiatry related information on Oxtr


High impact information on Oxtr


Biological context of Oxtr

  • Myometrial OTR mRNA levels increased at the end of gestation in Rlx+/+ but not Rlx-/- mice [11].
  • Whilst some of these regions had been described for rat or sheep, the OTR-LacZ reporter mouse enabled the identification of novel sites of central OTR gene expression [12].
  • We targeted the lacZ reporter gene to the OTR gene locus downstream of the endogenous OTR regulatory elements [12].
  • Using lactating mouse mammary gland as a control for OTR promoter directed specificity of lacZ gene expression, X-gal histochemistry on tissue sections confirmed that gene expression was restricted to the myoepithelial cells [12].
  • Hormone treatment had no effect on vasopressin mRNA expression in the PVN, but significantly increased OTR binding in both the VMN and the MeA in both genotypes [13].

Anatomical context of Oxtr

  • We also identified for the first time in mice the expression of the OTR gene in neighbouring adipocytes [12].
  • These results suggest that OT-induced uterine contraction is not only regulated by the quantity of OTR in the non-pregnant mouse uterus [14].
  • We also compared the effects of ovarian hormones on oxytocin receptor (OTR) expression in the medial amygdala (MeA) and ventromedial nucleus of the hypothalamus (VMN) in female WT and betaERKO mice [13].
  • Oxytocin receptor-mediated activation of phosphoinositidase C and elevation of cytosolic calcium in the gonadotrope-derived alphaT3-1 cell line [15].
  • Consistent with this hypothesis, luteal OT receptor expression exceeded that of the myometrium until luteolysis occurred [16].

Associations of Oxtr with chemical compounds

  • Estrogen receptor alpha is essential for induction of oxytocin receptor by estrogen [17].
  • On the contrary, progesterone and OTR expression are correlated [2].
  • Administration of an OT receptor antagonist (Atosiban, d[Dtyr(Et)(2), Thr(4)]ornithine vasotocin) 100 ng icv, to female OT+/+ mice increased anxiety-related behavior by decreasing the percentage of entries (P < 0.01) and time spent (P < 0.04) in the open arms compared with artificial cerebrospinal fluid-treated controls [18].
  • Furthermore, destruction of ventral striatal dopaminergic terminals with 6-hydroxydopamine infusions into the nucleus accumbens did not alter OTR binding [7].
  • Intron 3 interrupts the coding at the same location, after transmembrane domain 6, as in OTR genes of other species [19].

Physical interactions of Oxtr

  • OT receptor distribution and binding in brains of OT null and wild type mice were examined by autoradiography and were not significantly different [20].

Other interactions of Oxtr

  • Oxytocin, but not oxytocin receptor, is rRegulated by oestrogen receptor beta in the female mouse hypothalamus [13].
  • The unique promoter sequences of the prairie vole OTR and V1a receptor genes and the resulting species-specific pattern of regional expression provide a potential molecular mechanism for the evolution of pair bonding behaviors and a cellular basis for monogamy [21].
  • The present study evaluated the expression of four relatively well-localized molecules--renin, Tamm-Horsfall protein (THP), oxytocin receptor (OTR), and the vasopressin type 2 receptor (V2R)--in cultured mouse-rat chimeric metanephric kidneys using reverse transcription-polymerase chain reaction (RT-PCR) [22].
  • Pretreatment with oxytocin receptor antagonist centrally had no effect on ACTH responses to stress in either virgin or pregnant mice [23].
  • In fetal thymic organ cultures, OTR antagonist d[D-Tyr(Et)2, Thr4]OVT increased early apoptosis of CD8 cells, while V1bR antagonist (Sanofi SSR149415) inhibited T-cell differentiation, and favored CD8 T-cell commitment [24].

Analytical, diagnostic and therapeutic context of Oxtr


  1. 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]
  2. Oxytocin receptor within the breast: biological function and distribution. Sapino, A., Cassoni, P., Stella, A., Bussolati, G. Anticancer Res. (1998) [Pubmed]
  3. 111In-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-lys(8)-vasotocin: a new powerful radioligand for oxytocin receptor-expressing tumors. Bussolati, G., Chinol, M., Chini, B., Nacca, A., Cassoni, P., Paganelli, G. Cancer Res. (2001) [Pubmed]
  4. Neurohypophysial receptor gene expression by thymic T cell subsets and thymic T cell lymphoma cell lines. Hansenne, I., Rasier, G., Charlet-Renard, C.h., DeFresne, M.P., Greimers, R., Breton, C., Legros, J.J., Geenen, V., Martens, H. Clin. Dev. Immunol. (2004) [Pubmed]
  5. Expression of the oxytocin receptor in clinical human breast cancer tissues. Ito, I., Kimura, T., Wakasugi, E., Takeda, T., Kobayashi, T., Shimano, T., Kubota, Y., Makino, Y., Azuma, C., Saji, F. Adv. Exp. Med. Biol. (1995) [Pubmed]
  6. 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]
  7. Ventral striatopallidal oxytocin and vasopressin V1a receptors in the monogamous prairie vole (Microtus ochrogaster). Lim, M.M., Murphy, A.Z., Young, L.J. J. Comp. Neurol. (2004) [Pubmed]
  8. Species and individual differences in juvenile female alloparental care are associated with oxytocin receptor density in the striatum and the lateral septum. Olazábal, D.E., Young, L.J. Hormones and behavior. (2006) [Pubmed]
  9. 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]
  10. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. Matsuura, K., Nagai, T., Nishigaki, N., Oyama, T., Nishi, J., Wada, H., Sano, M., Toko, H., Akazawa, H., Sato, T., Nakaya, H., Kasanuki, H., Komuro, I. J. Biol. Chem. (2004) [Pubmed]
  11. Inhibition of oxytocin receptor and estrogen receptor-alpha expression, but not relaxin receptors (LGR7), in the myometrium of late pregnant relaxin gene knockout mice. Siebel, A.L., Gehring, H.M., Reytomas, I.G., Parry, L.J. Endocrinology (2003) [Pubmed]
  12. Mapping oxytocin receptor gene expression in the mouse brain and mammary gland using an oxytocin receptor-LacZ reporter mouse. Gould, B.R., Zingg, H.H. Neuroscience (2003) [Pubmed]
  13. 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]
  14. The differential coupling of oxytocin receptors to uterine contractions in murine estrous cycle. Kawamata, M., Tonomura, Y., Kimura, T., Yanagisawa, T., Nishimori, K. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  15. Oxytocin receptor-mediated activation of phosphoinositidase C and elevation of cytosolic calcium in the gonadotrope-derived alphaT3-1 cell line. Evans, J.J., Forrest-Owen, W., McArdle, C.A. Endocrinology (1997) [Pubmed]
  16. 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]
  17. Estrogen receptor alpha is essential for induction of oxytocin receptor by estrogen. Young, L.J., Wang, Z., Donaldson, R., Rissman, E.F. Neuroreport (1998) [Pubmed]
  18. Female oxytocin-deficient mice display enhanced anxiety-related behavior. Mantella, R.C., Vollmer, R.R., Li, X., Amico, J.A. Endocrinology (2003) [Pubmed]
  19. Structure and expression of the mouse oxytocin receptor gene. Kubota, Y., Kimura, T., Hashimoto, K., Tokugawa, Y., Nobunaga, K., Azuma, C., Saji, F., Murata, Y. Mol. Cell. Endocrinol. (1996) [Pubmed]
  20. 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]
  21. Oxytocin, vasopressin, and the neuroendocrine basis of pair bond formation. Insel, T.R., Winslow, J.T., Wang, Z., Young, L.J. Adv. Exp. Med. Biol. (1998) [Pubmed]
  22. Metanephric rat-mouse chimeras to study cell lineage of the nephron. Arend, L.J., Smart, A., Briggs, J.P. Dev. Genet. (1999) [Pubmed]
  23. Neuroendocrine responses to stress in mice: hyporesponsiveness in pregnancy and parturition. Douglas, A.J., Brunton, P.J., Bosch, O.J., Russell, J.A., Neumann, I.D. Endocrinology (2003) [Pubmed]
  24. Ontogenesis and functional aspects of oxytocin and vasopressin gene expression in the thymus network. Hansenne, I., Rasier, G., Péqueux, C., Brilot, F., Renard, C.h., Breton, C., Greimers, R., Legros, J.J., Geenen, V., Martens, H.J. J. Neuroimmunol. (2005) [Pubmed]
  25. Oxytocin receptors in brain cortical regions are reduced in haploinsufficient (+/-) reeler mice. Liu, W., Pappas, G.D., Carter, C.S. Neurol. Res. (2005) [Pubmed]
  26. Failure of parturition in mice lacking the prostaglandin F receptor. Sugimoto, Y., Yamasaki, A., Segi, E., Tsuboi, K., Aze, Y., Nishimura, T., Oida, H., Yoshida, N., Tanaka, T., Katsuyama, M., Hasumoto, K., Murata, T., Hirata, M., Ushikubi, F., Negishi, M., Ichikawa, A., Narumiya, S. Science (1997) [Pubmed]
  27. The comparative distribution of forebrain receptors for neurohypophyseal peptides in monogamous and polygamous mice. Insel, T.R., Gelhard, R., Shapiro, L.E. Neuroscience (1991) [Pubmed]
  28. Heterogeneity in the third intracytoplasmic region of the oxytocin receptor-encoding gene. Kaluz, S., Kaluzova, M., Flint, A.P. Gene (1996) [Pubmed]
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