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)

In the present work an attempt is made to get a deeper insight into the mechanism of labor and the events leading to the onset of labor by means of radioimmunological measurements of OT, PGE, PGF, PGEM and PGFM and by determining the oxytocin sensitivity and the concentration of oxytocin receptors. Prostaglandins play a major role for the mechanism of labor in labor of spontaneous onset as well as in several forms of induced labor (intravenous infusion of OT, amniotomy, local application of PGE2). The reason for this seems to be the 3 fold action of prostaglandins: stimulation of myometrial contractions, cervical softening, induction of gap junctions. Moreover prostaglandins produced in the placenta play a major role in the mechanism of placental separation and expulsion. Oxytocin seems to be of importance for the initiation of labor and the final expulsion of the fetus. Immediately before the onset of regular contractions a marked increase of oxytocin sensitivity can be demonstrated which correlates very well with an increase of oxytocin receptor concentration in the myometrium and decidua. Due to this increase in oxytocin sensitivity no rise in oxytocin plasma levels is necessary to induce labor. Apart from the induction of myometrial contractions oxytocin leads via receptors in the decidua to a stimulation of prostaglandin synthesis which can also be demonstrated in vitro. In cases of premature contractions the same mechanisms seem to be operational as at term, oxytocin and prostaglandins again playing a major role. Inhibition of contractions with ethanol is based on the capacity of alcohol to inhibit oxytocin secretion. The contractions inhibiting effect of ritodrine is mediated through the cAMP induced relaxation of the myometrium although possibly a direct reduction of prostaglandin synthesis by ritodrine is possible. Increasing estrogen and decreasing progesterone activities at term lead to multiple subtile changes leading to an increased prostaglandin synthesis and mainly to a rise in oxytocin receptor concentration in the myometrium and the decidua. Oxytocin from the fetal and maternal side stimulates contractions in the myometrium and prostaglandin synthesis in the decidua leading to the onset of labor. With progressing cervical dilatation prostaglandin synthesis is further stimulated; these prostaglandins together with the increased oxytocin plasma levels in the second stage of labor lead to expulsion of the fetus. After delivery prostaglandin synthesis in the placenta leads to placental separation and expulsion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The importance of oxytocin and prostaglandins to the mechanism of labor in humans]. 609 5

Rats were made unilaterally pregnant by tying the right oviduct on the day after mating, to compare the oxytocin receptor concentrations in a nondistended, nonpregnant uterine horn with those in a distended, pregnant horn. On day 20, they were subjected to bilateral ovariectomy and indwelling balloons were inserted into both uterine horns. Following ovariectomy, the rats were injected im with either oil, estradiol benzoate (5 micrograms/rat per 24 h), or estradiol and progesterone together. For comparison, intact rats were studied on days 21 and 22, 24 and 48 h after insertion of the indwelling balloons. Spontaneous uterine activity and the response to increasing amounts of oxytocin were recorded 20-24 h and 44-48 h after surgery, following which the uteri were excised and assayed for oxytocin and estrogen receptors. The oxytocin receptor concentrations in the two horns were different on day 20 before the treatments were begun, the distended pregnant horn having a higher concentration per milligram DNA than the nonpregnant horn. The various treatments always changed the oxytocin receptor concentrations in the same direction; estrogen increased and progesterone inhibited the estrogen-induced rise in oxytocin receptor concentrations. In intact rats, the distention-induced increase in oxytocin receptor concentrations present on day 20 disappeared near term, but in the absence of the ovaries distention of the uterus had a significant influence on the myometrial oxytocin receptor concentrations, potentiating the effect of estrogen. Progesterone selectively inhibited the distention-induced increase in oxytocin receptor concentrations without inhibiting the hypertrophic effect of distention in general. A good correlation between oxytocin receptor numbers and tissue responsiveness was observed in all instances. The changes in spontaneous activity induced by the various treatments were distinct from the changes in oxytocin responsiveness. Estrogen exerted a strong inhibitory action on the activity stimulated by hormone withdrawal, while progesterone had no inhibitory effect. The pregnant distended horn always showed more spontaneous activity than the nonpregnant horn. There was an overall significant correlation between nuclear estrogen receptor and oxytocin receptor concentrations per milligram DNA, although the partial correlations were not significant in all groups (oil and progesterone).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Systemic and local regulation of oxytocin receptors in the rat uterus, and their functional significance. 631 57

Incubation of uterine explants from immature rats with 0.01-100 ng of 17 beta-estradiol/mL resulted in approximately a fivefold increase in the number of oxytocin receptors per milligram of protein in 48 h. This increase was maintained for at least an additional 48 h in the presence of estrogen. When the explants were incubated with 1 microgram progesterone/mL from the outset, the concentration of oxytocin receptors was the same as initial (0 time) levels. The estrogen-induced increase in oxytocin receptor concentration was blocked by incubation with cycloheximide, an inhibitor of protein synthesis. Once increased, however, the concentration of oxytocin receptors exhibited no turnover for at least a 48-h period in the presence of estrogen. The addition of progesterone and estrogen to explants with elevated receptor levels resulted in almost a 60% reduction in oxytocin receptor concentration by 24 h, with no change in affinity of the receptor for oxytocin. The reduction in receptor concentration by progesterone was not prevented by cycloheximide. The progesterone effect may involve inactivation or degradation of oxytocin receptors or activation of substances that are inhibitory to oxytocin binding. The effects of estradiol and progesterone on oxytocin receptor concentration in uterine explants are similar to those seen when the steroids are administered in vivo. The explant system, therefore, should prove useful in clarifying factors and processes that are involved in regulation of oxytocin receptor concentration in the uterus and in the initiation of parturition in the rat.
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PMID:Regulation of oxytocin receptor concentration in rat uterine explants by estrogen and progesterone. 631 58

The significance of oxytocin for the onset of labour in humans is disputed, mainly because there is no increase in oxytocin concentration in the peripheral maternal blood before onset of labour. However, Fuchs et al. have recently shown that the concentration of oxytocin receptors in the myometrium is significantly higher directly before onset of labour than at the onset of spontaneous contractions. To establish a correlation with the clinical sensitivity to oxytocin, the authors determined the oxytocin sensitivity by means of intravenous administration of 3 X 10 m I.U. of oxytocin with continuous tocographic recording. Parallel to this determination, the cervical score was measured according to Bishop. The patients were 26 healthy pregnant women in whom both parameters were determined daily until onset of spontaneous labour pains. The sensitivity to oxytocin increased significantly during the last few days before spontaneous onset of labour. On the day before onset of pains, almost all of the pregnant women showed maximum sensitivity to oxytocin. Parallel to this, the cervical, scores also increased; on the day before onset of labour pains, almost all pregnant women had a cervical score of 5 or more than 5. On the basis of these results, which concur accurately with the results of measurement of oxytocin receptor concentrations, it is definitely possible to refute the arguments that oxytocin is irrelevant for the onset of labour because its concentration in the maternal plasma does not increase before the pains begin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Importance of oxytocin sensitivity for the spontaneous onset of human labor]. 631 69

Active immunization of sheep against oxytocin prolonged the luteal phase of the oestrous cycle, as judged by oestrous behaviour and circulating progesterone concentrations. Mean cycle length was extended by 3.7 days. The treatment resulted in a 10-fold increase in circulating oxytocin concentrations. Antisera produced were specific for oxytocin; cross-reactions with vasotocin, arginine vasopressin, and hypothalamic releasing factors were low. Cerebrospinal fluid contained low levels of antibodies directed against oxytocin. This finding supports the hypothesis that the luteolytic action of oestradiol-17 beta in sheep may be mediated through a stimulatory effect on the endometrial oxytocin receptor concentration.
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PMID:Delayed luteal regression in ewes immunized against oxytocin. 719 Jun 9

Oxytocinoic acid dimethylamide was synthesized by stepwise solution techniques as part of an ongoing evaluation of the effects on the biological activity of oxytocin caused by individually changing the groups that comprises the hydrophilic surface of the hormone to more hydrophobic and more bulky groups. The analogue exhibited approximately 3% of the potency of oxytocin in the in vitro uterotonic assay. In addition, it possesses potencies of less than 0.07, less than 0.01, and 0.096 unit/mg in the avian vasodepressor, rat pressor, and rat antidiuretic assays, respectively. In the in vitro uterotonic assay, oxytocinoic acid dimethylamide showed a reduced affinity for the oxytocin receptor, a nonparallel dose-response relationship, and most importantly a reduced intrinsic activity as compared to oxytocin. The results suggest that the replacement of the protons of the primary carboxyamide of Gly9-NH2 of oxytocin by methyl groups displaces the active elements from the orientation for obtaining maximal intrinsic activity in the isolated rat uterus.
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PMID:Effect of changing the COOH-terminal amide group present in the hydrophilic cluster of oxytocin to dimethylamide. 739 37

A new tritiated oxytocin antagonist radioligand was synthesized by introducing a tritiated propionic acid residue into the free amino group of ornithine in position 8 of the parent peptide [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine, 4-threonine, 8-ornithine, 9-tyrosylamide]vasotocin (OTA), that was previously described. The tritiated compound [3H][1-(beta-mercapto-beta,beta-cyclo-pentamethylene propionic acid), 2-(O-methyl)-tyrosine, 4-threonine, 8-(N6-propionyl)-ornithine, 9-tyrosylamide]vasotocin ([3H]PrOTA) was obtained in good yield with high specific activity (100 Ci/mmol). [3H]PrOTA exhibited the same affinity (Kd = 0.8 nM) and selectivity for the myometrial oxytocin receptor as the iodinated antagonist [125I]OTA. Autoradiographic localization of oxytocin receptors in the rat brain showed specific binding sites for [3H]PrOTA within regions of the limbic system, the neocortex, and hypothalamus, which is consistent with the binding pattern obtained with [125I]OTA. The high specific activity in combination with the long half-life of tritium and its low radiotoxicity as compared to iodine-125 makes the new tritiated antagonist a valuable tool for pharmacological studies.
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PMID:A new tritiated oxytocin receptor radioligand--synthesis and application for localization of central oxytocin receptors. 747 26

Luteolysis in sheep is associated with uterine secretion of pulses of prostaglandin F2 alpha (PGF2 alpha) due to the action of luteal oxytocin on endometrial oxytocin receptors. For pregnancy to become established inhibition of oxytocin receptors is important as an antiluteolytic mechanism. The maternal recognition of pregnancy in cattle and sheep involves production, by the trophoblast, of a type 1 interferon (IFN-tau) that suppresses uterine development of oxytocin receptors and the generation of luteolytic episodes of PGF2 alpha. The action of IFN-tau in surgically prepared unilaterally pregnant ewes was investigated. Finn-Dorset ewes were anaesthetized on day 6 or 7 of the oestrous cycle and one uterine horn was surgically isolated at the uterine bifurcation from the body of the uterus. Ewes were mated at the subsequent oestrus either by a fertile or by a vasectomized ram and killed on day 13 or 16 after mating. On day 16, in the non-pregnant ewes, there was no measurable uterine IFN-tau but there were high concentrations of oxytocin receptors in both horns. In the pregnant ewes on day 16 after mating, the oxytocin receptor concentration was 45 +/- 11 fmol mg-1 protein in the pregnant horn and 585 +/- 131 fmol mg-1 in the non-pregnant horn. Antiviral activity was 5.8 x 10(7) +/- 5.2 x 10(7) U ml-1 in the pregnant horn and 2.9 x 10(3) +/- 1.2 x 10(3) U ml-1 in the non-pregnant horn. Thus, 16 days after mating, the pregnant horn exhibited high antiviral activity but oxytocin receptors were suppressed, while in the same endocrine environment (characteristic of pregnancy) there were low IFN-tau and high oxytocin receptor concentrations in the isolated horn equivalent to those expected at the onset of luteolysis. In situ hybridization to ovine mRNA encoding the oxytocin receptor and autoradiographic studies using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin both showed that the large amount of oxytocin receptor message and binding sites in the endometrium of the isolated horn were localized in the luminal epithelium. Immunocytochemical studies showed that there was a suppression of oestradiol receptors in the pregnant horn but high concentrations equivalent to those at oestrus were present in the isolated horn. The content of progesterone receptors was low in the stromal tissue only in both horns, a pattern of localization similar to that seen in the late luteal phase and in early pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Local action of trophoblast interferons in suppression of the development of oxytocin and oestradiol receptors in ovine endometrium. 749 Jul 9

Oxytocin was identified in ovaries recovered on Day 5 (+/- 1) of the luteal phase from three female marmoset monkeys (Callithrix jacchus). With use of a reverse transcription-polymerase chain reaction assay, expression of mRNA for oxytocin and oxytocin receptor was detected in both luteal tissue and in the ovarian remnant. Evidence for ovarian synthesis of oxytocin was provided by immunohistochemistry, which showed positive staining for oxytocin and neurophysin in the cytoplasm of the luteal cells. Some luteal cells had a more intensely stained perinuclear region than others for oxytocin immunoreactivity, whereas the staining for neurophysin was evenly distributed. Granulosa and theca cells of antral follicles also showed positive staining for oxytocin immunoreactivity; no reactivity was found in fibroblast or endothelial cells. Oxytocin immunoreactivity was also detected in the luteal tissue of all animals by immunoassay, with values ranging from 2.8 to 12.1 ng/g wet weight. The oxytocin concentration for the ovarian remnant was either very low (0.55-0.75 ng/g wet weight) or nondetectable (< 0.5 ng/g wet weight). Local production of oxytocin within the ovary was suggested by the measurement of higher oxytocin concentrations in the blood from ovaries containing corpora lutea compared with peripheral blood. Collectively, these results provide evidence for ovarian biosynthesis of oxytocin and suggest the possibility of a paracrine role in the regulation of primate ovarian function.
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PMID:Oxytocin gene expression and oxytocin immunoactivity in the ovary of the common marmoset monkey (Callithrix jacchus). 752 74

We examined the key events underlying maternal recognition of pregnancy and the prevention of luteolysis in early postpartum ewes by synchronously transferring single expanded blastocysts recovered from control ewes on day 11 of pregnancy into the uterus of either postpartum recipients that had been induced to ovulate 28 days after lambing (n = 12) or control recipients (n = 11). Conceptus development uterine flush interferon (oTP-1) concentrations, endometrial oxytocin receptor concentrations and endometrial prostaglandin F2 alpha (PGF2 alpha) release in vitro were determined 5 days later (corresponding to day 16 of the ovarian cycle). By this stage, both conceptus mass and oTP-1 content of total uterine flush in the eight postpartum recipients that remained pregnant were significantly lower (P < 0.01) than in the eight pregnant control ewes (524 +/- 116.6 versus 959 +/- 80.6 mg and 968 +/- 16.9 versus 1512 +/- 106.2 ng oTP-1 for postpartum and control recipients, respectively). These effects were independent of ovulation rate and daily peripheral progesterone concentrations after blastocyst transfer, which were similar between groups. Endometrial oxytocin receptor density was variable in both groups when they were killed, and was generally higher in pregnant postpartum than in control recipients, and was significantly different (P < 0.05) when the values for the transfer but not the contralateral uterine horns were compared. Similarly, basal and oxytocin-stimulated endometrial PGF2 alpha release during a 4 h incubation were higher (P < 0.01) in pregnant postpartum versus control recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conceptus interferon in uterine flush, endometrial concentrations of oxytocin receptors and prostaglandin F2 alpha release in vitro after transfer of conceptuses to ewes induced to ovulate at 28 days postpartum. 754 44


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