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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently uncovered the presence of an oxytocin system in the heart and found that oxytocin is a physiological regulator of atrial natriuretic peptide (ANP), a diuretic, natriuretic and vasodilator cardiac hormone. However, dynamic changes in these systems during gestation, when mechanisms of volume and pressure homeostasis are altered, are not clear. Accordingly, ANP, oxytocin and oxytocin receptors were evaluated in rat hearts and plasma at three stages of gestation (7, 14 and 21 days) and at 2 and 5 days postpartum. Compared with non-pregnant controls, plasma ANP was elevated in mid-gestation, but significantly decreased at term (21 days), to increase again postpartum. Right and left atrial ANP mRNA levels were not altered throughout gestation but increased by 1.5- to 2-fold postpartum (P<0.01). At term, ANP content in right (8.7+/-1.2 vs 12.7+/-1.1 micro g/mg protein, P<0.04) and left (3.5+/-0.6 vs 8.5+/-2.0 micro g/mg protein, P<0.01) atria increased. These findings imply that decreased plasma ANP at term results from inhibition of release rather than decreased synthesis. In parallel, oxytocin, a stimulator of ANP release, decreased in left atria at day 7 to 50% of non-pregnant levels and remained low throughout gestation. Oxytocin receptor mRNA increased in left atria at 7 and 14 days of gestation by 2- and 5-fold respectively, but decreased at 21 days to lower than non-pregnant levels to increase again (3-fold) postpartum. The changes in oxytocin receptor expression at term and postpartum paralleled oxytocin receptor protein determined by Western blot. These results imply that pregnancy is associated with dynamic changes in the cardiac oxytocin system (peptide and/or receptors), which may influence natriuretic peptide release. Together, these peptides would act on their receptors in the heart, vasculature and kidneys to maintain vascular tone and renal function throughout gestation and postpartum.
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PMID:Regulation of cardiac oxytocin system and natriuretic peptide during rat gestation and postpartum. 1237 5

During parturition, the basal activity of the hypothalamo-pituitary-adrenal (HPA) axis of Wistar rats is strongly attenuated, whereas the oxytocin system is activated. We investigated the secretory responses of the HPA axis and oxytocin to exposure to a mild emotional stressor (airpuff) comparing virgin female, d 22 pregnant, and parturient rats. Furthermore, as the brain oxytocin system is activated in parturition and oxytocin has been shown to inhibit HPA axis responses in virgin rats, the role of brain oxytocin in the regulation of stress responses during parturition was investigated by intracerebroventricular administration of an oxytocin receptor antagonist before stressor exposure (0.75 micro g/5 micro l). In virgin female rats, exposure to airpuff increased ACTH (2.5 +/- 0.34-fold) and corticosterone (5.1 +/- 2.3-fold) secretion, but in late pregnancy and parturition, the stress-induced increase in ACTH (pregnancy: 1.9 +/- 0.41-fold; parturition: 1.3 +/- 0.13-fold) and corticosterone secretion (parturition: 1.8 +/- 0.40-fold) were strongly attenuated. Oxytocin secretion remained unchanged in response to airpuff in both virgin and parturient rats despite higher overall plasma concentrations in the latter. Oxytocin receptor blockade in the brain elevated basal and stress-induced ACTH secretion in virgin but not pregnant or parturient rats and had no effect on oxytocin secretion either in virgin or parturient rats. We conclude that the reactivity of the HPA axis to external stressors is strongly attenuated during parturition, and this cannot be disinhibited by blocking the receptor-mediated action of brain oxytocin.
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PMID:No stress response of the hypothalamo-pituitary-adrenal axis in parturient rats: lack of involvement of brain oxytocin. 1274 9

Cocaine administered chronically throughout gestation has been correlated with deficits in maternal behavior, increased maternal aggressive behavior and decreased oxytocin levels in rats. In addition to its effects on oxytocin levels, cocaine is a potent serotonergic, dopaminergic and noradrenergic reuptake inhibitor. Alterations in the dopaminergic and serotonergic systems have been suggested as possibly having a role in cocaine-induced maternal aggression. This study was in part, an attempt to understand some of the mechanisms by which cocaine increases postpartum aggression, particularly as they relate to changes in the oxytocin system. Oxytocin receptor number and binding affinity in the medial preoptic area of the hypothalamus, ventral tegmental area, hippocampus and amygdala were determined for lactating rat dams on postpartum day 6 (PPD 6) that were gestationally treated with cocaine, fluoxetine, saline or an amfonelic acid/fluoxetine drug combination. Cocaine and fluoxetine treatment both resulted in a significant up-regulation of oxytocin receptor number and lower receptor affinity in the amygdala of lactating rat dams compared to saline controls and the amfonelic acid/fluoxetine combination treatment group. Cocaine treatment also resulted in a significant down-regulation of oxytocin receptors in the medial preoptic area and both cocaine and fluoxetine treated dams had the highest affinity for oxytocin receptors in this brain region. Results of the present study support previous data indicating that alterations in oxytocinergic and perhaps serotonergic system dynamics in the amygdala may play a role in cocaine-induced postpartum aggression.
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PMID:Gestational treatment with cocaine and fluoxetine alters oxytocin receptor number and binding affinity in lactating rat dams. 1538 Aug 31

In the proestrous female rat, norepinephrine, oxytocin and nitric oxide (NO) all participate in the regulation of the preovulatory gonadotropin-releasing hormone (GnRH) surge. Recent studies from our laboratory have demonstrated that oxytocin induces dose-dependent release of GnRH from proestrous basal hypothalamus explants. The present studies were undertaken to determine whether norepinephrine could also stimulate GnRH release from similar explants, to identify the receptors responsible for this effect and to investigate interactions between norepinephrine, oxytocin and NO. Norepinephrine significantly stimulated GnRH release from proestrous basal hypothalamus explants, and coadministration of the alpha(1)-adrenergic antagonist prazosin blocked this effect. Combined administration of oxytocin and norepinephrine stimulated significantly more GnRH release than either drug alone, and this stimulation was blocked by inhibition of NO synthase, or by an oxytocin receptor antagonist. NO production was measured from the same samples using a modified Griess reaction. Oxytocin, but not norepinephrine, significantly increased NO production, as did norepinephrine and oxytocin in combination. Oxytocin receptor antagonist administration attenuated the stimulation of NO production by norepinephrine/oxytocin. These results demonstrate for the first time that oxytocin and norepinephrine dramatically stimulate GnRH release from basal hypothalamus explants harvested on the afternoon of proestrus, and indicate that this involves oxytocin receptor and NO-dependent mechanisms.
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PMID:Interaction between norepinephrine, oxytocin, and nitric oxide in the stimulation of gonadotropin-releasing hormone release from proestrous rat basal hypothalamus explants. 1550 May 41

Oxytocin and the nucleus accumbens have been extensively implicated in the regulation of maternal behavior, and the processing of pup-related stimuli relevant for this behavior. Oxytocin receptor density in the nucleus accumbens is highly variable in virgin female prairie voles, as is their behavioral response to pups, ranging from neglecting and infanticidal to full maternal behavior. We hypothesized that oxytocin receptor in the nucleus accumbens facilitates the expression of "spontaneous" maternal behavior in prairie voles. Forty sexually-naive adult females were exposed to pups for the first time and tested for maternal behavior. Oxytocin receptor binding in the nucleus accumbens and other brain regions was later determined using autoradiography. Females that showed maternal behavior (lick and groom the pups and hover over them for at least 30 s, n=24) had higher oxytocin receptor density in the nucleus accumbens (shell subregion) (P<0.05) than females that did not show maternal behavior or attacked the pups (n=16). No differences were found in other brain regions (medial preoptic area, septum, prelimbic cortex). In a second experiment, we tested whether infusions of the oxytocin receptor antagonist (d(CH2)5(1),Tyr(Me)2,Orn8)-AVT into the nucleus accumbens would block "spontaneous" maternal behavior. As a control region, oxytocin receptor antagonist was also infused into the caudate putamen. Ten females were infused bilaterally into the nucleus accumbens or caudate putamen with either 2 ng/0.5 microl of oxytocin receptor antagonist or CSF (vehicle). While five of 10 nucleus accumbens CSF-infused animals showed maternal behavior, none of the nucleus accumbens oxytocin receptor antagonist-infused subjects did (0/10; chi2, P<0.01). Nucleus accumbens oxytocin receptor antagonist-infused females recovered the next day and were not different from controls. Animals infused with CSF or oxytocin receptor antagonist into the caudate putamen did not differ (four/10, four/10). This is the first study to show that the nucleus accumbens is involved in the regulation of "spontaneous" maternal behavior and that oxytocin receptor in this brain region facilitates maternal responses.
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PMID:Oxytocin receptors in the nucleus accumbens facilitate "spontaneous" maternal behavior in adult female prairie voles. 1672 74

Oxytocin receptor (OTR) is a membrane protein known to mediate oxytocin (OT) effects, in both normal and neoplastic cells. We report here that human osteosarcoma (U2OS, MG63, OS15 and SaOS2), breast cancer (MCF7), and primary human fibroblastic cells (HFF) all exhibit OTR not only on the cell membrane, but also in the various nuclear compartments including the nucleolus. Both an OTR-GFP fusion protein and the native OTR appear to be localized to the nucleus as detected by transfection and/or confocal immunofluorescence, respectively. Treatment with oxytocin causes internalization of OTR and the resulting vesicles accumulate in the vicinity of the nucleus and some of the perinuclear OTR enters the nucleus. Western blots indicate that OTR in the nucleus and on the plasma membrane are likely to be the same biochemical and immunological entities. It appears that OTR is first visible in the nucleoli and subsequently disperses within the nucleus into 4-20 spots while some of the OTR diffuses throughout the nucleoplasm. The behaviour and kinetics of OTR-GFP and OTR are different, indicating interference by GFP in both OTR entrance into the nucleus and subsequent relocalization of OTR within the nucleus. There are important differences among the tested cells, such as the requirement of a ligand for transfer of OTR in nuclei. A constitutive internalization of OTR was found only in osteosarcoma cells, while the nuclear localization in all other tested cells was dependent on ligand binding. The amount of OTR-positive material within and in the vicinity of the nucleus increased following a treatment with oxytocin in both constitutive and ligand-dependent type of cells. The evidence of OTR compartmentalization at the cell nucleus (either ligand-dependent or constitutive) in different cell types suggests still unknown biological functions of this protein or its ligand and adds this G-protein-coupled receptor to other heptahelical receptors displaying this atypical and unexpected nuclear localization.
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PMID:Constitutive and ligand-induced nuclear localization of oxytocin receptor. 1736 4

Oxytocin receptor (OTR) expression is suppressed by progesterone (P4) during the luteal phase of the estrous cycle and then it increases at the time of luteolysis, but its regulation is still not completely understood. The objective of this work was to characterize P4 metabolism by endometrial cells in vitro and determine if metabolites were able to modify prostaglandin secretion in response to oxytocin (OT). Endometrial epithelial and stromal cells were incubated with 3H-P4 or 3H-pregnenolone (P5) for 6 or 24 h. Metabolites in the medium were separated by HPLC. The results showed that P4 and P5 were converted to two major polar metabolites and a less polar metabolite that was identified as 5alpha- or 5beta-pregnanedione by LC/MS. Progesterone metabolism was similar in both stromal and epithelial cells. To determine if 5alpha- or 5beta-pregnanedione were able to modify PGF(2)alpha synthesis, cells were cultured with P4, 5alpha- or 5beta-pregnanedione (100 ng ml(-1)) for 48 h and then each group of cells was incubated for a further 4-6 h with or without OT (200 ng ml(-1)). Results showed that only P4 caused significant (P<0.001) increase in basal, but not OT-stimulated, PGF(2)alpha synthesis. OT binding assays showed no significant effect of progesterone or its metabolites on OTR concentration. In conclusion, bovine endometrial cells are able to metabolize pregnenolone and progesterone but neither 5alpha- nor 5beta-pregnanedione altered prostaglandin synthesis or OTR number in endometrial epithelial cells. These data suggest that 5-pregnanediones do not play a role in the regulation OT-stimulated PGF(2)alpha secretion during the bovine estrous cycle.
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PMID:Progesterone metabolism in bovine endometrial cells and the effect of metabolites on the responsiveness of the cells to OT-stimulation of PGF2alpha. 1776 41

Oxytocin is a mammalian hormone that is released mainly after distension of the uterine cervix. In this study, we report that oxytocin stimulates intracellular release of calcium, and also activates AMPK (AMP-activated protein kinase) in C2C12 myoblast cells in a time/dose-dependent manner. Oxytocin receptor mRNA was detected in C2C12 cells. In addition, oxytocin stimulated glucose uptake and, moreover, inhibition of either CaMKK (Ca(2+)/calmodulin-dependent protein kinase kinase) or AMPK blocked oxytocin-mediated AMPK activation and glucose uptake. Taken together, our findings suggest that oxytocin may serve a peripheral metabolic function in skeletal muscle cells through the calcium-CaMKK-AMPK pathway.
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PMID:Oxytocin stimulates glucose uptake in skeletal muscle cells through the calcium-CaMKK-AMPK pathway. 1855 43

Oxytocin is synthesized and released in the heart and vasculature, tissues that also express oxytocin receptors. Although it has been established this intrinsic cardiovascular oxytocin system is important in normal homeostatic cardiac and vascular regulation, a role for this system in cardiovascular pathophysiology has not been investigated. The current study examined the influence of oxytocin on mechanisms in atherogenesis, oxidative stress, and inflammation in cultured human vascular cells, THP-1 monocytes, and macrophages. Oxytocin receptor protein and mRNA expression, NADPH-dependent superoxide activity, and interleukin-6 secretion were measured. Results demonstrated oxytocin receptor protein and mRNA in THP-1 monocytes and macrophages. Incubation of cells at physiological levels of oxytocin significantly decreased basal and stimulated NADPH-dependent superoxide activity in vascular cells, monocytes, and macrophages by 24-48%. Oxytocin also attenuated interleukin-6 secretion from stimulated THP-1 macrophages and endothelial cells by 56 and 26%, respectively. These findings suggest that oxytocin attenuates vascular oxidative stress and inflammation, two important pathophysiological processes in atherosclerosis. The fact that oxytocin receptors are found in monocytes and macrophages, and oxytocin decreases both superoxide production and release of a proinflammatory cytokine from these cells, suggests a potentially larger role for oxytocin in the attenuation of disease.
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PMID:Oxytocin attenuates NADPH-dependent superoxide activity and IL-6 secretion in macrophages and vascular cells. 1894 Sep 36

Oxytocin receptors in the nucleus accumbens have been implicated in the regulation of alloparental behavior and pair bond formation in the socially monogamous prairie vole. Oxytocin receptor density in the nucleus accumbens is positively correlated with alloparenting in juvenile and adult female prairie voles, and oxytocin receptor antagonist infused into the nucleus accumbens blocks this behavior. Furthermore, prairie voles have higher densities of oxytocin receptors in the accumbens than nonmonogamous rodent species, and blocking accumbal oxytocin receptors prevents mating-induced partner preference formation. Here we used adeno-associated viral vector gene transfer to examine the functional relationship between accumbal oxytocin receptor density and social behavior in prairie and meadow voles. Adult female prairie voles that overexpress oxytocin receptor in the nucleus accumbens displayed accelerated partner preference formation after cohabitation with a male, but did not display enhanced alloparental behavior. However, partner preference was not facilitated in nonmonogamous meadow voles by introducing oxytocin receptor into the nucleus accumbens. These data confirm a role for oxytocin receptor in the accumbens in the regulation of partner preferences in female prairie voles, and suggest that oxytocin receptor expression in the accumbens is not sufficient to promote partner preferences in nonmonogamous species. These data are the first to demonstrate a direct relationship between oxytocin receptor density in the nucleus accumbens and variation in social attachment behaviors. Thus, individual variation in oxytocin receptor expression in the striatum may contribute to natural diversity in social behaviors.
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PMID:Variation in oxytocin receptor density in the nucleus accumbens has differential effects on affiliative behaviors in monogamous and polygamous voles. 1919 78


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