Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the physiological significance of tumor necrosis factor alpha (TNFalpha) in the regulation of luteolytic prostaglandin (PG) F(2alpha) release by the bovine endometrium, the effect of TNF-alpha on PGF(2alpha) output by the endometrial tissues in vitro was investigated and compared with the effect of oxytocin (OT). Furthermore, the presence of specific receptors for TNFalpha in the bovine endometrium during the estrous cycle was determined. Endometrial slices (20-30 mg) taken from six stages of the estrous cycle (estrus: Day 0; early I: Days 2-3; early II: Days 5-6; mid-: Days 8-12; late: Days 15-17; and follicular: Days 19-21), as determined by macroscopic examination of the ovaries and uterus, were exposed to TNFalpha (0.06-6 nM) and/or OT (100 nM). OT stimulated PGF(2alpha) output at the follicular stage and at estrus (P < 0.001), but not at the late luteal stage. On the other hand, the stimulatory effects of TNFalpha on PGF(2alpha) output were observed not only at the follicular stage but also at the late luteal stage (P < 0.001). When the endometrial tissues at late luteal stage were simultaneously exposed to TNFalpha (0.6 nM) and OT (100 nM), the stimulatory effect on PGF(2alpha) output was higher than the effect of TNFalpha or OT alone (P < 0.05). Specific binding of TNFalpha to the bovine endometrial membranes was observed throughout the estrous cycle. The concentration of TNF-alpha receptor at the early I luteal stage was less than the concentrations at other luteal stages (P < 0.01). The dissociation constant (K(d)) values of the endometrial membranes were constant during the estrous cycle. The overall results lead us to hypothesize that TNFalpha may be a trigger for the output of PGF(2alpha) by the endometrium at the initiation of luteolysis in cattle.
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PMID:Is tumor necrosis factor alpha a trigger for the initiation of endometrial prostaglandin F(2alpha) release at luteolysis in cattle? 1077 55

This study explored the possible beneficial effects of singing on well-being during a singing lesson. Eight amateur (2m, 6f, age 28-53 yrs) and eight professional (4m, 4f, age 26-49 yrs) singers who had been attending singing lessons for at least six months were included. Continuous ECG was recorded and computerized spectral analysis was performed. Serum concentrations of TNF-alpha, prolactin, cortisol, and oxytocin were measured before and 30 min after the lesson. Five visual analogue scales (VAS, sad-joyful, anxious-calm, worried-elated, listless-energetic, and tense-relaxed) were scored before and after the lesson. In addition, a semi-structured interview was performed. Heart rate variability analyses showed significant changes over time in the two groups for total power, and low and high frequency power. Power increased during singing in professionals, whereas there were no changes in amateurs. This indicates an ability to retain more "heart-brain connection." i.e., more cardio-physiological fitness for singing in professional singers, compared to amateur singers. Serum concentration of TNF-alpha increased in professionals after the singing lesson, whereas the concentration in amateurs decreased. Serum concentrations of prolactin and cortisol increased after the lesson in the group of men and vice versa for women. Oxytocin concentrations increased significantly in both groups after the singing lesson. Amateurs reported increasing joy and elatedness (VAS), whereas professionals did not. However, both groups felt more energetic and relaxed after the singing lesson. The interviews showed that the professionals were clearly achievement-oriented, with focus on singing technique, vocal apparatus and body during the lesson. The amateurs used the singing lessons as a means of self-actualization and self-expression as a way to release emotional tensions. In summary, in this study, singing during a singing lesson seemed to promote more well-being and less arousal for amateurs compared to professional singers, who seemed to experience less well-being and more arousal.
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PMID:Does singing promote well-being?: An empirical study of professional and amateur singers during a singing lesson. 1281 97

Placental leucine aminopeptidase (P-LAP), a type-II transmembrane protease responsible for oxytocin degradation during pregnancy, is converted to a soluble form through proteolytic cleavage. The goal of this study was to determine the nature of the P-LAP secretase activity. The hydroxamic acid-based metalloprotease inhibitors GM6001 and ONO-4817 as well as the TNF-alpha protease inhibitor-2 (TAPI-2) reduced P-LAP release, while tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, which are matrix metalloproteinase inhibitors, had no effect on P-LAP release in Chinese hamster ovary (CHO) cells stably overexpressing P-LAP, thus indicating possible involvement of ADAM (a disintegrin and metalloproteinase) members in P-LAP shedding. Furthermore, overexpression of ADAM9 and ADAM12 increased P-LAP release in P-LAP-CHO transfectants. Immunohistochemical analysis in human placenta demonstrated strong expression of ADAM12 in syncytiotrophoblasts, while little expression of ADAM9 was detected throughout the placenta. Our results suggest ADAM members, at least including ADAM12, are involved in P-LAP shedding in human placenta.
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PMID:ADAMs, a disintegrin and metalloproteinases, mediate shedding of oxytocinase. 1475 Dec 33

Maternal plasma leptin concentration is significantly increased during pregnancy. However, its roles in pregnancy, especially in labor, have not been fully clarified. We measured plasma leptin concentrations in pregnant women during the course of induced labor, just after spontaneous vaginal delivery and Cesarean section at term. We also studied the regulation of leptin secretion from term placental tissue and BeWo cells, a trophoblastic cell-line. Plasma leptin concentrations increased significantly during labor (58.9 +/- 9.2 ng/ml) compared to those before labor induction (37.5 +/- 5.8 ng/ml, P<0.05), then decreased 3-6 days postpartum (14 +/- 3 ng/ml, n = 6, P<0.0001) to the levels of normal nonpregnant women. Leptin concentrations within an hour and 24 hours after spontaneous vaginal delivery were significantly higher than those after Cesarean section (P<0.05 for both comparisons). Similarly, leptin mRNA expression in placental tissues obtained after spontaneous vaginal delivery was significantly greater than that in those obtained after Cesarean section without labor (P<0.05). IL-1alpha and TNF-alpha treatment significantly stimulated leptin secretion and leptin mRNA expression in explant culture of human term placental tissue and in BeWo cells as compared with those in vehicle controls (P<0.05, for all comparisons). By contrast, oxytocin and prostaglandin F(2alpha) treatment had no effects on leptin secretion from explant culture of human term placental tissue or from BeWo cells. These data indicate that pro-inflammatory cytokines might stimulate placental leptin secretion, thus finally contributing to the increase in plasma leptin concentration during labor.
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PMID:Significant increase in maternal plasma leptin concentration in induced delivery: a possible contribution of pro-inflammatory cytokines to placental leptin secretion. 1511 68

Oxytocin-induced Ca(2+) transients play an important role in myometrial contractions. Here, using a knockout model, we found that the enzyme CD38, responsible for the synthesis of the second messenger cyclic ADP-ribose (cADPR), plays an important role in the oxytocin-induced Ca(2+) transients and contraction. We also observed that CD38 is necessary for TNF-alpha-increased agonist-stimulated Ca(2+) transients in human myometrial cells. We provide experimental evidence that the TNF-alpha effect is mediated by increased expression of the enzyme CD38. First, we observed that TNF-alpha increased oxytocin-induced Ca(2+) transients and CD38 expression in human myometrial cells. Moreover, using small interference RNA technology, we observed that TNF-alpha stimulation of agonist-induced Ca(2+) transients was abolished by blocking the expression of CD38. In control experiments, we observed that activation of the component of the TNF-alpha signaling pathway, NF-kappaB, was not affected by the treatments. Finally, we observed that the effects of TNF-alpha on CD38 cyclase and oxytocin-induced Ca(2+) transients are abolished by progesterone. In conclusion, we provide the first experimental evidence that CD38 is important for myometrial Ca(2+) transients and contraction. Moreover, CD38 is necessary for the TNF-alpha-mediated augmentation of agonist-induced Ca(2+) transients in myometrial cells. We propose that the balance between cytokines and placental steroids regulates the expression of CD38 in vivo and cell responsiveness to oxytocin.
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PMID:Role of CD38 in myometrial Ca2+ transients: modulation by progesterone. 1533 43

Increased concentrations of IL-1beta and TNF-alpha have been associated with parturition. However, the role of these cytokines is unknown. Before parturition, the uterus undergoes a process of activation, during which there are significant changes in expression of genes associated with increased uterine contractility, including the receptors for oxytocin (OT) and prostaglandin (PG)F(2alpha) (FP), PGH(2) synthase isoform 2 (PGHS2), the gap junction protein connexin-43 (Cx-43), and the inducible isoform of nitric oxide synthase (iNOS). To determine whether IL-1beta or TNF-alpha was part of the causal mechanism for increased uterine contractions, we placed osmotic pumps infusing IL-1beta or TNF-alpha into the peritoneal cavity of late pregnant rats (gestation day 19) and measured the effects on uterine contractility and on the uterine concentrations of mRNA for the contraction-associated genes 24 h later. Maternal serum concentrations of IL-1beta and TNF-alpha were increased significantly. By day 21, the control animals had significant increases (P < or = 0.05) in mRNA for OT, FP, PGHS2, and Cx-43, a decrease (P < or = 0.05) in iNOS, and an increase (P < or = 0.05) in uterine sensitivity and responsiveness to OT. Infusion of IL-1beta or TNF-alpha had no effect on uterine contractility or on expression of the activation-associated genes. We conclude that intraperitoneal infusion of IL-1beta or TNF-alpha resulting in significantly increased maternal serum cytokine levels does not cause uterine activation. The role of proinflammatory cytokines in the mechanism of parturition remains unclear.
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PMID:Intraperitoneal infusion of proinflammatory cytokines does not cause activation of the rat uterus during late gestation. 1587 Jan 3

Factors which induce the corpus luteum persistent (CLP) creation in animal ovaries are located in the hypothalamic-pituitary-ovarian axis and also in the uterus. In cows and likewise in others animals, various mediators of inflammatory reaction are released, mainly proinflammatory cytokines from inflamed uterus into the blood and lymph. Afterwards the cytokines cross the blood-brain barrier, and though the brain mediators alter the hormonal profile and amplitude pulses of the hormones release in the hypothalamus and the pituitary. Until it is known, that cytokines: IL-1, IL-2, IL-6, TNF-alpha and also IFN-alpha, administered into the median eminence, cause an increase in corticotrophin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) concentrations and decrease in the pituitary gland hormones secretion. The immune system, represented in the corpora lutea (CL) by numerous macrophages/monocytes, limphocytes and neutrophils plays an important role in the luteolysis process. The stimulating factor of the infiltration of these cells is an increased PRL level. The preovulatory increase in PRL level regulates the number of macrophages in newly-formed CL and later influences the number of these cells in the luteolysis period. The pulsatory release and high levels of the hypophyseal oxytocin (OT) and uterine PGF2alpha ensure the beginning and the normal course of the luteolysis period. The cytokines decrease OT concentration and disorder its pulsatory release from the pituitary. In these circumstances the quantity of the uterine PGF2alpha reaching ovaries, is insufficient to begin luteolysis. In the inflamed uterus, the elevation of PGE2 and PGI2 synthesis takes place. Both prostaglandins cause smooth uterine muscles relaxation and the dilatation of blood and lymph vessels in this organ. In these conditions, the blood and lymph outflow from the uterus is several times slower than in the control animals. The secretion of P4 and E2 from CLP, in comparison with control animals, is significantly lower. Decreased P4 concentration during the luteal phase of the estrous cycle, and E2 in the initiation of the luteolysis period, may cause the insufficient preparation of the endometrium for hypophyseal OT activity. Finally, we can assume that the creation of the CLP in the animal ovary is an exceptionally complex and not yet fully understood process.
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PMID:Immuno-endocrine mechanisms connected with the creation of corpora lutea persistent in animal ovaries. 1618 May 88

Transient splanchnic vasoconstriction following major burns causes oxidative and/or nitrosative damage in gastrointestinal tissues due to ischemia, which is followed by reperfusion injury. Oxytocin (OT), a hypothalamic nonapeptide, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in immune and inflammatory processes. To assess the possible protective effect of oxytocin (OT) against burn-induced gastric injury, Sprague-Dawley rats (250-300g) were randomly divided into three groups as control (n=8), OT-treated burn (n=8) and saline-treated burn (n=8) groups. Under anesthesia, the shaved dorsal skin of rats was exposed to 90 degrees C water for 10s to induce burn injury covering 30% of total body surface area in a standardized manner. Either oxytocin (5microg/kg) or saline was administered subcutaneously immediately after and at 24h following burn, and the rats were decapitated at 48h. Serum samples were assayed for TNF-alpha, and stomach was taken for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, DNA fragmentation rate (%) and histopathological examination. MDA and MPO were assayed for products of lipid peroxidation and as an index of tissue neutrophil infiltration, respectively. When compared to control group, burn caused significant increases in gastric MDA and MPO activity and increased microscopic damage scores at 48h (p<0.001). Oxytocin treatment reversed the burn-induced elevations in MDA and MPO levels and reduced the gastric damage scores (p<0.001, p<0.01), while TNF-alpha levels, which were increased significantly at 48thh after injury (p<0.001), were abolished with OT treatment (p<0.001). The results of this study suggest that oxytocin may provide a therapeutic benefit in diminishing burn-induced gastric inflammation by depressing tissue neutrophil infiltration and decreasing the release of inflammatory cytokines, but requires further investigation as a potential therapeutic agent in ameliorating the systemic effects of severe burn.
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PMID:Oxytocin ameliorates skin damage and oxidant gastric injury in rats with thermal trauma. 1782 14

Various mechanisms have been proposed for the pathogenesis of postischemic hepatic injury, including the generation of reactive oxygen metabolites. Oxytocin (OT) possesses antisecretory, antiulcer effects, facilitates wound healing and has anti-inflammatory properties. Hepatic ischemia-reperfusion (I/R)-injury was induced by inflow occlusion to median and left liver lobes ( approximately 70%) for 30 min of ischemia followed by 1h reperfusion in female Sprague-Dawley rats under anesthesia. I/R group (n=8) was administered intraperitoneally either OT (500 microg/kg) or saline at 24 and 12 h before I/R and immediately before reperfusion. Sham-operated group that underwent laparotomy without hepatic ischemia served as the control. Rats were decapitated at the end of reperfusion period. Hepatic samples were obtained for the measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH) and collagen levels and histopathological analysis. Tumor necrosis factor-alfa (TNF-alpha) and transaminases (SGOT, SGPT) were assayed in serum samples. I/R injury caused significant increases in hepatic microscopic damage scores, MPO activity, collagen levels, transaminase, serum TNF-alpha levels. Oxytocin treatment significantly reversed the I/R-induced elevations in serum transaminase and TNF-alpha levels and in hepatic MPO and collagen levels, and reduced the hepatic damage scores. OT treatment had tendency to abolish I/R-induced increase in MDA levels, while GSH levels were not altered. These results suggest that OT has a protective role in hepatic I/R injury and its protective effect in the liver appears to be dependent on its inhibitory effect on neutrophil infiltration.
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PMID:Oxytocin alleviates hepatic ischemia-reperfusion injury in rats. 1840 49

Oxytocin is a hormone and neurotransmitter found to have anti-inflammatory functions in rodents. Here we used experimental bacterial endotoxinemia to examine the role of exogenous oxytocin administration on innate immune responses in humans. Ten healthy men received, in a randomized, placebo-controlled, crossover design, placebo, oxytocin, LPS, and LPS + oxytocin. Oxytocin treatment resulted in a transient or prolonged reduction of endotoxin-induced increases in plasma ACTH, cortisol, procalcitonin, TNF-alpha, IL-1 receptor antagonist, IL-4, IL-6, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, monocyte chemoattractant protein-1 (MCP-1), interferon-inducible protein 10, and VEGF. In vitro, oxytocin had no impact on LPS effects in releasing TNF-alpha, IL-6, and MCP-1 in monocytes and peripheral blood mononuclear cells from healthy human donors. In summary, oxytocin decreases the neuroendocrine and cytokine activation caused by bacterial endotoxin in men, possibly due to the pharmacological modulation of the cholinergic anti-inflammatory pathway. Oxytocin might be a candidate for the therapy of inflammatory diseases and conditions associated with high cytokine and VEGF levels.
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PMID:Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men. 1859 51


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