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

• Oxytocin is an important modulator of female reproductive functions including parturition, lactation and maternal behavior, while vasopressin regulates water balance and acts as a neurotransmitter [7].
• Neither OT nor AOT affected response latencies in mice not given the footshock on the training trial, indicating that the actions of both treatments on retention performance were not due to nonspecific proactive effects on response latencies [8].
• Therefore, the OT, ER-alpha, and ER-beta genes are necessary, to different degrees, for social discrimination and, thus, for the modulation of social behavior (e.g. aggression, affiliation) [9].
• Involvement of estrogen receptor alpha, beta and oxytocin in social discrimination: a detailed behavioral analysis with knockout female mice [9].
• These findings support the hypothesis that absence of OT results in a heightened response of the HPA axis to certain stressors and that OT can attenuate the corticosterone response associated with overnight food or water deprivation in male mice [10].

High impact information on Oxt

• Brain oxytocin (OT) and vasopressin (AVP) seem to modulate a range of social behaviour from parental care to mate guarding [11].
• Social amnesia in mice lacking the oxytocin gene [11].
• Oxytocin, prolactin and hydrocortisone, which slowed or blocked involution, produced parallel effects on gland regression and PA synthesis [12].
• This result may be partly due to defective neuronal connectivity, as well as reduced oxytocin neurons in the hypothalamus, because mutant mothers were deficient in milk ejection [13].
• Several neurotransmitter-containing neurons in the rat paraventricular nucleus coexpress ERbeta including; vasopressin, oxytocin, prolactin, and to a lesser extent corticotrophin releasing hormone [14].

Chemical compound and disease context of Oxt

• Oxytocin-deficient mice not only displayed more anxiety-related behaviour, but also released more corticosterone after a psychogenic stressor and manifested greater stress-induced hyperthermia compared to wild-type mice [15].
• This behavioral effect may be mediated by estrogen-induced increases in OT binding density in the lateral septum and may be important to the facilitation of social interactions [16].
• Oxytocin, a neurohypophyseal neuropeptide, also partially antagonized cocaine-induced motor hyperactivity [17].
• On the mode of action of an oxytocin derivative (Z-Pro-D-Leu) on morphine-dependence in mice [18].
• Finally, the oxytocin blocker, atosiban, reduced both operant and reflexive social behavior [19].

Biological context of Oxt

• Interspecific backcross analysis has now been used to map the Avp/Oxt complex to chromosome 2 in the mouse [20].
• Neither plasma OXT levels under several different conditions nor OXT messenger RNA expression in the paraventricular nucleus were different between the genotypes [21].
• Oxytocin binding sites were most noticeable in the hypothalamic ventromedial nucleus, in the amygdaloid complex and in restricted areas of the cerebral cortex [22].
• Estrogen modulates oxytocin gene expression in regions of the rat supraoptic and paraventricular nuclei that contain estrogen receptor-beta [7].
• Relaxin decreases oxytocin-stimulated rat myometrial contractions in vitro [23].

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

• Collectively, the findings in the present study suggest that oxytocin may regulate stress-induced CRH gene expression in the PVN [32].
• We have previously demonstrated that the oxytocin (OT) gene is expressed in the rat uterine epithelium and that its expression is upregulated in vivo and in vitro by estrogen [33].
• OT-positive neurons expressed Fos in dehydrated wild-type mice, and vasopressin-positive neurons were activated to a similar extent in wild-type and OT -/- mice [34].
• Cholecystokinin and D-fenfluramine inhibit food intake in oxytocin-deficient mice [35].
• Contractions to oxytocin were completely blocked by the calmodulin antagonists trifluoperazine (50 microM) and W-7 (75 microM) [36].

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

• To assess the ability of estrogen to modulate the expression of oxytocin mRNA, ovariectomized rats were treated with vehicle or estradiol and the brains processed for in situ hybridization [7].
• Subsequent double-label in situ hybridization/immunocytochemistry studies showed that ER-beta mRNA was present in oxytocin and vasopressin neurons, with the degree of colocalization being both neuropeptide and region specific [7].
• Immediate posttraining subcutaneous injection of OT (0.01, 0.03, 0.10, 0.30, and 1.00 microg/kg) impaired retention performance [8].
• Reverse transcription-polymerase chain reaction (RT-PCR) analysis detected V1b and oxytocin, but not V1a or V2, receptor transcripts in mouse islet cells [38].
• Molecular ion species with masses characteristic of oxytocin, AVP, neurophysin I and II, i.e. 1009.41, 1084.5, 9677 and 9679 daltons respectively, were identified in all but the oxytocin-Null mice by comparison with synthetic standards or by C-terminal sequence analysis [39].

References