Disease relevance of Oxtr

• We demonstrated OTR expressions in the large majority of ovarian carcinoma tissues, and OT inhibited not only proliferation but also migration and invasion in ovarian carcinoma cells in vitro [1].
• There is no correlation among OTR presence in breast carcinomas and the age of patients, tumor stage, estrogen receptor positivity, oncogene expression and proliferation rate of the same tumor [2].
• The present study opens new perspectives for imaging and, possibly, therapy of OTR-positive human tumors such as breast and endometrial carcinomas, neuroblastomas, and glioblastomas [3].
• Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment [4].
• Expression of the oxytocin receptor in clinical human breast cancer tissues [5].

Psychiatry related information on Oxtr

• Adult Oxtr(-/-) males also showed deficits in social discrimination and elevated aggressive behavior [6].
• Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior [6].
• Oxytocin receptors (OTR) and vasopressin V1a receptors (V1aR) in the ventral forebrain play critical roles in the formation of pair bonds in the monogamous prairie vole [7].
• Species and individual differences in juvenile female alloparental care are associated with oxytocin receptor density in the striatum and the lateral septum [8].

High impact information on Oxtr

• These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior [6].
• Oxtr(-/-) dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing [6].
• Oxtr(-/-) mice were viable and had no obvious deficits in fertility or reproductive behavior [6].
• Activation of cardiac OTR stimulates the release of atrial natriuretic peptide (ANP), which is involved in regulation of blood pressure and cell growth [9].
• The cardiac Sca-1+ cells expressed oxytocin receptor mRNA, and the expression was up-regulated after oxytocin treatment [10].

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

• RESULTS: Our findings reveal that the oxytocin receptor (OTR), measured either by immunohistochemistry or in situ hybridization, is significantly lower in HRM [25].
• METHODS: In this study we used immunocytochemistry and in situ hybridization in HRM versus wild-type (+/-) mice (WTM) to quantify OTR abundance in regions of the brain cortex [25].
• Ovariectomy at day 19 of pregnancy restored induction of the oxytocin receptor and permitted successful delivery in the FP-deficient mice [26].
• Using in vitro receptor autoradiography with the selective oxytocin receptor ligand [125I]d(CH2)5[Tyr(Me)2,Tyr-NH9(2)]OVT ([125I]OTA), we compared Peromyscus maniculatus, a polygamous species, to Peromyscus californicus, a monogamous species [27].
• We have now confirmed, by sequencing polymerase chain reaction (PCR)-derived genomic fragments coding for the OTR 3ICR from a variety of ruminant and non-ruminant species, that additional aa are a general phenomenon in ruminants [28].

References