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

The uterotonic action of oxytocin has been known for many decades. This neurohypophysial hormone is thought to play a functional role in human parturition. Since 1968, prostaglandins have also been implicated in parturition. These two groups of uterotonic agents have now a recognized therapeutic role, and are widely used in the induction of labour and in fertility control. However, the mechanism of action and the interrelationship between these endogenous compounds in pregnancy are poorly understood. In this article, the role and interaction of oxytocin, oxytocinase and prostaglandins in human pregnancy and labour have been reviewed. Inhibition of oxytocinase activity by prostaglandins has been suggested as a mechanism in parturition. Possible involvement of cyclic GMP in the initiation of labour has also been discussed.
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PMID:Review: significance of the inhibition by prostaglandins and cyclic GMP of oxytocinase activity in human pregnancy and labour. 630 40

Triglycyl-oxytocin (TGOT) and oxytocin (OT) were administered iv and sc to conscious dogs and the plasma concentrations of these peptides determined simultaneously by RIA and bioassay. Constant iv infusions (1 h) at 23 pmol/kg/min produced plateau levels of 1.1 and 1.6 pmol/ml plasma for OT and TGOT respectively. Whilst the distribution space was similar for each peptide. TGOT persisted longer in the circulation (t1/2, for TGOT 6.6 min; for OT 4.2 min). Bioactive values for OT followed RIA values whether this peptide was given iv or sc. Although very little bioactivity was generated by iv infusions of TGOT, considerable amounts of bioactive OT were found in plasma after injection of TGOT subcutaneously. The hormonogen proved relatively resistant to oxytocinase, an enzyme that destroys OT rapidly. Our results indicate that TGOT is converted to OT in vivo and that its action as a hormonogen is more pronounced after sc than iv administration.
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PMID:Activation and clearance of a hormonogen, triglycyl-oxytocin, in the conscious dog. 705 81

1. Plasma oxytocin concentrations were measured by radioimmunoassay in 231 normal pregnant patients. The mean level of the maternal plasma oxytocin increases gradually with advancing pregnancy, culminating in a marked increase during the last two months. 2. Serum placental leucine aminopeptidase (P-LAP) activities and oxytocinase were measured serially in 78 obstetrically normal pregnant patients during late pregnancy. The daily mean P-LAP activity rises progressively during late pregnancy, reaching a relatively high level at 11 days prior to the onset of labor, then fluctuates slightly until the onset of labor. 3. Simultaneous serial measurements of plasma oxytocin levels and serum P-LAP activities in 9 normal pregnant women during late pregnancy show that the onset of labor is preceded by either an increase in the oxytocin level or a decrease in the P-LAP activity.
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PMID:Simultaneous determinations of plasma oxytocin and serum placental leucine aminopeptidase (P-LAP) during late pregnancy. 711 22

This study was designed to evaluate the fetal oxytocin (OT) contribution to the instigation and maintenance of human labor. Plasma samples together with placental tissues and myometria were collected in an effort to determine immunoreactive OT concentrations in plasma, oxytocinase activities in placenta and 3H-labeled OT uptake in myometria respectively and the following results were obtained. OT concentrations in the umbilical arterial plasma (UA) at 20 to 24 weeks were doubled at 37 to 42 weeks suggesting the increase of this hormone to occur in the latter half of pregnancy. The UA values at term were significantly higher than that of maternal peripheral and umbilical venous plasma (MPV and UV). OT concentrations in UA and UV showed a linear correlation but not with MPV. The study of labor (+) and labor (-) subjects were performed in cesarean sections as well as in vaginal deliveries. The OT concentrations in UA was higher in cesarean sections with labor pains than without labor pains. In vaginal deliveries, the OT concentrations were much higher. The uptake of biologically active OT estimated by 3H-labeled OT uptake of 20,000 xg precipitate fraction of nonpregnant, first trimester and term myometria were 10.5 plus or minus 3.1, 18.3 plus or minus 6.6 and 35.4 plus or minus 6.6% respectively. While no significant changes of placental oxytocinase activities were found between these specimens. The activities seemed to be lower in cases without labor pain than those with labor pains. These findings suggest that there is OT release from the fetus during labor to participate in the instigation and maintenance of labor with increase of the uterine sensitivity to OT, however it appears to be more active in maintaining labor than in initiating it.
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PMID:[Initiation of labor and the fetal oxytocin contribution (author's transl)]. 721 Dec 27

In a group of 26 primiparae, 48 hours after cesarean section, we have examined the urinary estriol (E3) and serum cystine aminopeptidase (CAP). 13 patients received ampicillin treatment, and 13 patients did not. In the group of patients without antibiotic treatment the urinary estriol after 48 h reached an average value of 5.55 mg/24 h. in the group of treated patients the drastic decrease of E3 reached a mean value of 1.62 mg/24 h. This fact may be explained by the arrest of the feto-placental inflow after delivery, and the blocking effect of the antibiotic on the enterohepatic circulation, compartment which afford for 50% of the maternal circulating estrogen. From the present work it results that the determination of the serum CAP activity, which is not affected by antibiotic treatment, is an appropriate test for the assessment of the fetoplacental unit activity. It must be mentioned that all the biochemical tests complete one another and may have a decisive role in taking immediate obstetrical decisions, together with the additional fetal heart rate monitoring and oxytocin challenge test.
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PMID:Oxytocinase versus estriol for the assessment of fetal well-being. 725 50

1. Among the simple manual methods for recording intrauterine retardation repeated measurements of the symphysis-fundus distance according to Westin are most valuable. -- 2. Among the hormone-determining methods the estimation of urinary estrogens or unconjugated estriol in serum is generally accepted. -- 2. Estimations of enzymes are of no value (diamine oxidase, alkaline leukocyte phosphatase, heat stable alkaline phosphatase) or have only little significance (cystine aminopeptidase). -- 4. Biochemical methods are being replaced to an increasing extent by biophysical ones both for recording fetal retardation by ultrasonics and fetal well-being by CTG, non-stress test, oxytocin-challenge test and, recently, by registration of fetal breathing and rump movements. -- 5. As a provisional method for evaluation of fetal behaviour the counting of fetal movements by the pregnant women herself can be recommended.
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PMID:[Contribution towards diagnostics of intrauterine fetal retardation (author's transl)]. 746 67

An aminopeptidase from porcine kidney, hydrolyzing oxytocin and vasopressin in vitro, was purified by chromatography on hydroxyapatite, DEAE-cellulose and nickel ion chelate gel and gel filtration on Sephadex G-100. The enzyme appeared to be a high molecular mass (M(r) 105,000) monomeric protein. It was sensitive to inhibition by metal chelator, o-phenanthroline. Cobalt ion and sulfhydryl activator, 2-mercaptoethanol, had activating effects, while p-chloromercuribenzoate, amino acids with large hydrophobic side chains, L-cystine and aminopeptidase inhibitors, bestatin and amastatin, had inhibitory effects on the enzyme activity. The enzyme hydrolyzed several aminoacyl p-nitroanilides, and had the highest specificity against S-benzyl-L-cysteine p-nitroanilide. The properties of the enzyme were distinct from those of well-characterized leucyl aminopeptidase (EC 3.4.11.1), membrane alanyl aminopeptidase (EC 3.4.11.2) and primate placental cystinyl aminopeptidase (EC 3.4.11.3).
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PMID:An aminopeptidase activity from porcine kidney that hydrolyzes oxytocin and vasopressin: purification and partial characterization. 787 63

This investigation was conducted to evaluate the potential capacity of the human fetal membranes-decidua parietalis, and in particular the chorion laeve, to degrade uterotonins that are produced in amnion, are present in amniotic fluid, or both. The four uterotonins that have been evaluated most frequently as myometrial contractants potentially involved in the initiation of human parturition are prostaglandins, oxytocin, endothelin-1, and platelet-activating factor. We assessed the levels of mRNA and the specific activities (SAs) of enkephalinase (the plasma membrane endopeptidase that degrades endothelins) and prostaglandin dehydrogenase (PGDH) in human fetal membranes, i.e. amnion and chorion leave, and in decidua parietalis. The SA of oxytocinase (which inactivates oxytocin) in these tissues also was determined. The SA of enkephalinase in chorion laeve from all anatomical sites (singleton and diamnionic-dichorionic twin placentae) in all pregnancies studied (mean +/- SEM, 95 +/- 7.9 ng/min.mg protein; n = 28) is similar to that in human fetal kidney (89.5 +/- 2.8; n = 6). Kidney tissue is believed to be one of the richest sources of enkephalinase. The SAs of enkephalinase in amnion (18.3 +/- 2.3 nmol/min.mg protein; n = 29) and in decidua parietalis (31.8 +/- 6.7; n = 20) also were high, but significantly less than that in chorion leave. The level of enkephalinase mRNA in chorion laeve in singleton pregnancies is high, as is the SA of enkephalinase (111.9 +/- 10.6 nmol/min.mg protein; n = 17). In paired chorion laeve tissues from five diamnionic-dichorionic twin placentae, the SAs of enkephalinase in reflected chorion laeve (74 +/- 12.8; P < 0.06 compared with singletons) and fused chorion laeve (64.8 +/- 6.5; P < 0.001 compared with singletons) were similar. The SA of PGDH in reflected chorion leave (46.3 +/- 6.9 nmol/min.mg protein; n = 19) was significantly greater than that in decidua (16 +/- 5.5; n = 15). There was a significant correlation between the levels of PGDH mRNA and PGDH enzyme SA. In fused chorion laeve of diamnionic-dichorionic twin placentae, the SA of PGDH (14.9 +/- 7.3; n = 4) was much less than that in reflected chorion laeve of the same twin pregnancy (70.5 +/- 14.7; n = 4). PGDH mRNA was not detectable in amnion tissue (n = 5) by northern analysis, and the SA of PGDH (< 1.2 +/- 1.0; n = 6) in amnion was undetectable or near the lower limit of assay detection.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human fetal membrane contribution to the prevention of parturition: uterotonin degradation. 810 36

Several studies in the past few years have supported the hypothesis that oxytocin (OT) is synthesized in a paracrine system within the pregnant human uterus and that this paracrine system may be an important regulator of the timing of human parturition. Using ribonuclease protection assays, we have demonstrated a three-fold increase in the rate of synthesis of OT mRNA in human decidua around the time of parturition. We also have shown that a similar increase in OT mRNA and peptide synthesis can be stimulated in vitro by physiological concentrations of estradiol. This increase is inhibited by concomitant use of the estrogen receptor (ER) blocker tamoxifen or by transcription inhibitors. Progesterone had little, if any effect. We also detected mRNAs for ER and progesterone receptor (PR) in amnion, chorion and decidua with the same relative tissue concentrations as OT mRNA. The concentrations of ER but not PR increased significantly around the time of labour onset. To determine if local OT concentrations may be regulated by changes in OT metabolism, we determined kinetic parameters for OT metabolism in decidua, chorion and placenta. [3H]tyrosyl-OT was used as substrate. Metabolites were separated using HPLC and identified using amino acid analysis and mass spectrometry. Metabolism in decidua and chorion occurred predominantly via a cytosolic post-proline endopeptidase and the activity was comparable to placenta. In microsomal fractions, cystine aminopeptidase activity predominated and placenta had significantly more activity than decidua and chorion. There were no changes in any Km or apparent vmax values around the time of parturition. These findings support the existence of a paracrine system within human decidua that involves sex steroids regulating synthesis of OT and that undergoes significant changes around the time of parturition. Changes in local OT concentrations are controlled by rates of synthesis rather than rates of metabolism.
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PMID:Synthesis and metabolism of oxytocin in late gestation in human decidua. 871 92

Oxytocin (OX) has been suggested as a signal for parturition. Although OX is produced by both mother and fetus, concentrations are higher in umbilical than maternal blood. In addition, umbilical artery OX concentrations (15-40 pg/ml) are higher than umbilical vein (4-12 pg/ml) and maternal (1-10 pg/ml) concentrations. The umbilical A-V difference suggests that placental uptake and transport may be one path from fetal (F) to maternal (M) circulation. However, this difference may also reflect placental oxytocinase activity, which is known to metabolize biologically active peptides such as OX. We have investigated placental transport of OX from F to M and M to F circulation using in vitro dually perfused isolated cotyledons from term human placenta. Term human placentae from uncomplicated pregnancies were obtained immediately after delivery. A single peripheral cotyledon and corresponding lobule was cannulated and perfused. After stabilization and demonstration of adequate M to F perfusion-perfusion overlap, we studied the transport of OX (3H) with 14C-inulin (14C-IN) as permeability reference in both M to F (n = 8) and F to M (n = 6) directions during 2 h of perfusion. In addition to the higher tissue uptake observed in M to F than F to M transport direction as measured by the drop in the concentration of both 3H-OX and 14C-IN in the circuits in which both compounds were added, the same trend was found for the transfer rates of both compounds. These transfer rates which reflect the permeability of placental tissue to OX and IN were 15.17 +/- 2.79 (mean +/- SD) and 6.28 +/- 0.93 microliters/min/g (M to F) and 11.79 +/- 1.77 and 4.91 +/- 0.81 microliters/min/g (F to M). Although the permeability of both compounds is higher in the M to F than in the F to M transport direction, comparing these permeability values with respect to their molecular weight (MW) showed a significant correlation when known permeability values of polar compounds between MW 60 and 68,000 daltons were included. This correlation indicates that OX crosses the placenta in both directions by simple diffusion. High-performance liquid chromatography analysis showed that there is little evidence of placental metabolism and degradation of OX over the period of these experiments. Oxytocin is the main therapeutic drug that is frequently used in obstetrics for the induction of labor and parturition. Under such circumstances and with respect to the placental permeability results, oxytocin could reach the fetal circulation.
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PMID:Human placental transport of oxytocin. 893 Jul 95


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