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)

Recently, we have described a chorionic peptidase (C-ase-1) which inactivates gonadotropin releasing hormone (GnRH), oxytocin, angiotensin II and thyrotropin releasing hormone. Since all these hormones contain a proline residue, we proposed that C-ase-1 may act as a post-proline peptidase. Using HPLC and amino acid analyses, we have defined the products which resulted from enzymatic inactivation of GnRH by C-ase-1. The N-terminal nonapeptide of GnRH was isolated by HPLC and confirmed by amino acid composition analyses. Thus, it was demonstrated that C-ase-1 acts as a post-proline peptidase when inactivating GnRH, yielding the nonapeptide, i.e., des-Gly10-NH2-GnRH, and Gly-NH2. The levels of intrauterine GnRH, angiotensin II, oxytocin and thyrotropin releasing hormone may be affected and integrated by this enzyme. Thus, C-ase-1 may play an important role in the regulation of the paracrine and endocrine function during pregnancy.
Placenta
PMID:Chorionic peptidase inactivates GnRH as a post-proline peptidase. 150 38

The interactions of corticotrophin releasing factor (CRF) and oxytocin on myometrial contractility were studied in isolated gestational myometrium in vitro. Acting alone oxytocin showed a significant dose related inotropic effect (P less than 0.001), whereas CRF did not. Dose-response curves of oxytocin in the presence of a fixed dose of CRF showed a threefold increase in the response to oxytocin without CRF present (P = 0.0019). When this combined priming and potentiating effect was investigated separately, priming of the myometrial strips with CRF prior to stimulation with oxytocin significantly enhanced the inotropic effect of oxytocin (P = 0.01) and when given together a significant potentiating effect was seen (P = 0.008). It is suggested that placental CRF may act as an important modulator of the inotropic effect of oxytocin on myometrium. The interaction between the two peptides may be similar to that which occurs between CRF and vasopressin in the anterior pituitary gland.
Placenta
PMID:Placental corticotrophin releasing factor may modulate human parturition. 278 79

The activation of placental AC by either Mg2+ or Mn2+, in the presence and absence of NaF, followed sigmoidal saturation kinetics. Mn2+ enhanced maximally the NaF-stimulated Mg2+-dependent AC activity. The apparent Km of Mg2+-dependent AC for ATP was 0.4 mM, with and without NaF addition. GTP and GMP-P(NH)P stimulated the Mg2+-dependent AC in a dose-dependent manner with half-maximal stimulation taking place at concentrations of approximately 2 microM. In the presence of GMP-P(NH)P (10 microM) the kinetics of the AC dependence on Mg2+ ion concentration changed from sigmoidal to hyperbolic. Most of the AC activity (greater than 83 per cent) was associated with the particulate fractions of placental homogenate. For better reproducibility, the AC assay was performed using sonicated particulate fraction preparations; sonication did not alter the response of AC to stimuli to a variety of agents used in these experiments; freezing and thawing, however, obliterated the stimulation by beta-adrenergic agonists. Placental AC activity was inhibited by p-hydroxymercuriphenyl sodium sulphonate in a dose-dependent fashion, and the inhibition was reversed by dithiothreitol. Mg2+-dependent AC was inhibited by 0.5 mM phenylhydrazine (95 per cent). Mg2+-dependent AC activity was responsive to stimulation by epinephrine, without and with GTP addition, with half-maximal stimulation taking place at a concentration of 2 microM. The stimulatory effect of epinephrine was blocked by propranolol in a dose-dependent manner but was not blocked by phentolamine. Oestrone, oestradiol-17 beta, 2-hydroxyoestreone, 2-hydroxyoestradiol-17 beta, dehydroepiandrosterone sulphate, and progesterone, as well as oxytocin, did not alter either the basal or GMP-P(NH)P-stimulated Mg2+-dependent AC activities. Preincubation of 20 000 g particulate fraction with either NaF or GMP-P(NH)P, followed by washing, resulted in preparations that remained stimulated without the requirement of any further additions.
Placenta
PMID:Adenylate cyclase from term human placenta and its regulation. 712 27

The aim of the present study was to investigate the presence of the immunoreactive oxytocin in human placental extracts and putative factors regulating the release of immunoreactive oxytocin from cultured human placental cells. Fresh placental tissue was collected from pregnant women at term and dissected of membranes (n = 5). Presence of immunoreactive oxytocin in trophoblast tissue was evaluated by a specific radio-immunoassay after acidic extraction and high-pressure liquid chromatography. In a second set of experiments, primary cultures of placental cells were performed and, 48-72 h after dissociation, the effect of arginine vasopressin, corticotropin-releasing factor, neuropeptide Y, activin A, inhibin A, noradrenaline or prostaglandins on immunoreactive oxytocin level in culture medium was investigated. The presence of immunoreactive oxytocin was shown in the acidic extract of trophoblast at term, and in the culture medium of human placental cells, and it was identical to the native peptide. The addition of corticotropin-releasing factor or arginine vasopressin, but not of neuropeptide Y, increased the release of immunoreactive oxytocin three- to fourfold from placental cells, with a dose-dependent effect (P < 0.01). A significantly increased release of immunoreactive oxytocin was shown in presence of noradrenaline (P < 0.01), which was reversed by prazosin, an antagonist of alpha-adrenergic receptors. Recombinant human activin A (P < 0.01), but not inhibin A, stimulated the release of immunoreactive oxytocin three- to fourfold from placental cells. Prostaglandin F2 alpha was a potent secretagogue of immunoreactive oxytocin, whereas a partial or no effect was observed when prostaglandin E2 or prostaglandin I2 was added. Thus, the present findings showed that human placenta contains immunoreactive oxytocin, and that its release from cultured placental cells is regulated by neurohormones, growth factors or prostaglandins.
Placenta
PMID:Activin A, corticotropin-releasing factor and prostaglandin F2 alpha increase immunoreactive oxytocin release from cultured human placental cells. 882 13

Human placenta is a major source of corticotropin-releasing factor (CRF), and local effects of CRF in fetal membranes and placenta have been shown, i.e., adrenocorticotropic hormone (ACTH) and oxytocin release from cultured placental cells, as well as prostaglandin release from amnion, chorion and decidua. Two distinct CRF receptors (CRF-R1 and CRF-R2) have been characterized: CRF-R1 consists of two isoforms (CRF-R1alpha and CRF-R1beta) while CRF-R2 has at least three different splice variants (CRF-R2alpha, CRF-R2beta and CRF-R2gamma). To date, CRF-R1 receptor has been identified in human placenta and in pregnant myometrium, while no evidence for placental CRF-R2 receptor isoforms has been provided. The present study investigated whether the different isoforms of CRF-R1 and CRF-R2 receptor mRNA are expressed in fetal membranes and placenta. Tissues were collected after spontaneous vaginal delivery (38-40 weeks) or elective caesarean section (39-41 weeks). The gene expression of CRF receptors was first studied by reverse transcriptase-polymerase chain reaction (RT-PCR), and the presence of CRF-R1alpha, but not of CRF-R1beta, in human placental trophoblast, amnion/chorion and decidua was shown. In addition, among the three CRF-R2 splice variants, only CRF-R2beta mRNA was expressed by trophoblast and fetal membranes. By using in situ hybridization, CRF-R1 and CRF-R2 probes positively hybridized trophoblast and related membranes. CRF-R1 was localized in the syncytiotrophoblast cells, chorionic trophoblast and decidua with a small amount in the amnion. CRF-R2 probe mainly hybridized syncytiotrophoblast cells, but cytotrophoblast also contained discreet amounts of CRF-R2 mRNA signal. The CRF-R2 hybridization signal was also observed within the structure of the villi (blood vessels), chorionic trophoblast and decidual cells, but it was faint or absent in the amniotic epithelium. There was no significant difference in the distribution of CRF-R1 or CRF-R2 mRNA signal between placentas collected from vaginal delivery or caesarean section. The evidence that intrauterine tissues differently express CRF-R1alpha and CRF-R2beta supports possible different local roles of CRF and related peptides into intrauterine tissues during pregnancy.
Placenta 2000 Jan
PMID:Human placenta, chorion, amnion and decidua express different variants of corticotropin-releasing factor receptor messenger RNA. 1069 48

The influence of oxytocin (OXY), sulproston (SUL) and acetylsalicylic acid (ASA) on L-alanine- (ALA), D-glucose- (GLU) or water- (H(2)O) uptake (maternal side) in the isolated perfused guinea pig placenta was investigated. Uptake was measured with a single injection, paired tracer dilution method. 'T50' values were derived from venous concentration curves (extracellular marker) as the distance (sec) between two concentration values at 50 per cent of peak concentration. T50 values were regarded to reflect the change of flow distribution on the maternal side. On average, there was a significant apparent inhibition of GLU uptake (by 27.2 per cent from control values) by OXY as well as of ALA uptake by OXY (26. 0 per cent), by ASA (56.6 per cent), and by SUL (56.7 per cent). The respective mean T50 values decreased significantly in the above groups by 15.9 per cent, 18.7 per cent (ns), 42.2 per cent and 56.7 per cent. However, it was not possible to generate dose-response curves whereas significant correlations of uptake values with T50 values were found. There was no dose-response relationship between T50 values and OXY or ASA concentrations but decreased mean T50 values were found. For SUL a weak correlation of T50 and SUL concentration was found. The r -value of GLU uptake and T50 was 0.57, for H(2)O uptake this value was 0.70, for ALA uptake the r -values were 0.51 (OXY), 0.35 (SUL) and 0.31 (ASA). Correlation of uptake and concentrations were not significant. We conclude that the 'inhibitory' effects of OXY, ASA and probably SUL on placental transfer are unspecific and the consequence of flow shifts from the placental exchange area to the uterine muscle.
Placenta 2000 Jan
PMID:The effect of oxytocin, prostaglandin E2 and acetylsalicylic acid on flow distribution and on the transfer of alanine, glucose and water in isolated perfused guinea pig placentae. 1069 61

The aim of this study was to evaluate the relationship between the occurrence of retention of the fetal membranes (RFM) and the hormonal concentrations of progesterone, estradiol-17beta, prostaglandin E(2) (PGE(2)), prostaglandin F(2alpha) (PGF(2alpha)), oxytocin (OT), oxytocin receptor (OT-R), endothelin-1 and angiotensin II (Ang II) in the placental tissues of cattle. Parturition was induced in nine Holstein cows by a single injection of PGF(2alpha) on Day 274 of gestation. Six out of nine cows in the induced group did not release the fetal membranes within 12 h after parturition and served as the RFM group, and the remaining three cows in that group, which released their fetal membranes within 12 h, served as the non-RFM group. Five other cows calved spontaneously and served as controls. The placental tissues were collected immediately (0 h) and at 6 h after parturition. The hormonal concentrations were measured by enzyme immunoassay in maternal and fetal placental tissues from RFM, non-RFM and control cows. There were no differences in P4 and E2 concentrations among the RFM, non-RFM and control groups. The mean PGF(2alpha) concentration of the RFM group was lower than those of the non-RFM and control groups in the maternal part of the placenta. In maternal tissues, the OT and OT-R concentrations in the RFM group were lower than those at 0 and 6 h after parturition in the non-RFM group. Additionally, the Ang II concentration of the RFM group in both the maternal and fetal parts of placental tissues tended to be higher than those of the other groups. In conclusion, the present results suggest that ET-1 and Ang II may play differential tissue-specific roles in the placental unit that may amplify the local endocrinological cascade involving OT, OT-R and PGF(2alpha) interactions which are necessary for normal placental separation in the cow.
Placenta 2002 May
PMID:Bovine retained placenta: hormonal concentrations in fetal and maternal placenta. 1206 59

Placental leucine aminopeptidase (P-LAP)/oxytocinase (OTase) degrades several small peptides such as oxytocin (OT), arginine vasopressin (AVP) and angiotensin III (ANGIII), and aminopeptidase A (AP-A) converts angiotensin II (ANGII) to ANGIII. These proteases play an important role in foetal growth and the maintenance of human homeostasis during pregnancy. In this study, we confirmed the distribution of P-LAP and AP-A proteins and messenger RNAs in human trophoblasts in normal placenta and complete hydatidiform mole by immunohistochemical and in-situ hybridization techniques. Immunoreactivity of P-LAP was mainly noted in the apical membrane of syncytiotrophoblasts, and the expression of messenger RNA (mRNA) for P-LAP was predominantly noted in the cytoplasm of syncytiotrophoblastic cells. However, immunoreactivity of AP-A was mainly noted in the apical membrane of cytotrophoblasts and in the basal zone of the syncytiotrophoblasts, and the expression of mRNA for AP-A was predominantly noted in cytoplasm of cytotrophoblastic cells and a little in cytoplasm of syncytiotrophoblastic cells. Thereby, the two proteases were differentially distributed both in normal placenta and hydatidiform mole throughout the gestational age. These results are useful for the further understanding of not only the pathophysiology of pregnancy, but also the pathogenesis of trophoblastic diseases.
Placenta
PMID:Differential distribution of placental leucine aminopeptidase/oxytocinase and aminopeptidase A in human trophoblasts of normal placenta and complete hydatidiform mole. 1236 82

The development of a multicellular spheroid comprising bovine endometrial epithelial cells (BEE) and bovine endometrial stromal cells (BES) is described in this study. The BES were cultured to confluence in medium with L -ascorbic acid phosphate magnesium salt n -hydrate (AsA-P) which stimulates collagen synthesis in BES. The BEE were co-cultured on a BES cell-sheet for 24h before detachment of the cell-sheet to generate a hetero-spheroid. After EDTA treatment and agitating with pipette, the floating cell-sheet shrank and became an aggregated cell mass in a few days; it finally formed a round-shaped hetero-spheroid composed of BES and BEE. Histological examination found that hetero-spheroids were covered with BEE on the outer layer. When cell viability was examined with TUNEL (terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling), no positive signal was detected in the spheroid for up to 10 days. Immunofluorescence observations showed that spheroids contained abundant extracellular matrices, including type-I, -III, -IV collagen, fibronectin, and laminin. PGF(2alpha) produced by hetero-spheroids in response to oxytocin was significantly higher than those produced by monolayer cultured BEE (P< 0.05). MMPs were not detected in media from spheroids cultured for 5 days after detachment of the cell sheet. These results indicate that bovine endometrial cells have the capacity to regenerate as a multicellular spheroid after treatment with ascorbate in vitro. The spheroid displays an endometrium-mimic feature. Thus, we conclude that spheroids formed by BES and BEE are a useful in vitro model of bovine endometrium.
Placenta
PMID:A three-dimensional cell culture model for bovine endometrium: regeneration of a multicellular spheroid using ascorbate. 1256 53

Our study aimed to explore the relevant risk factors for intrauterine death of fetuses in the third trimester of pregnancy via a retrospective analysis. Then, 98 pregnant women with intrauterine death of fetuses in the third trimester of pregnancy were enrolled, who had undergone the induced labor of dead fetuses in our hospital from January, 2013 to January, 2015. By taking their disease conditions into considerations, methods of induced labor as softening of cervix with dinoprostone suppositories and amniotic infusion of ethacridine or oxytocin were performed, and the timely cesarean section for termination of pregnancy was performed. After the treatment, a detailed medical history was recorded, including their family history, past history and conditions of this pregnancy. Besides, autopsy of dead fetuses and pathological examinations were performed as well as chromosome examinations of the placenta, the umbilical cord and the fetal membrane in an attempt to identify the relevant factors for causes of death, so as to do a good job in the post-natal consultation. The induced labor procedures were successfully performed on all pregnant women, and the investigation of causes of intrauterine death showed that placental factors were responsible for the largest proportion of all causes of intrauterine death in single (28 patients), which was 31.82%, including 13 patients with placenta praevia and 13 with placental abruption. The secondary factors were umbilical cord factors, accounting for 30.68%. Among the factors of pregnant women, gestational hypertension occurred in 7 patients, accounting for 58.33% of factors of pregnant women. While among the causes of intrauterine death in twins, umbilical cord factors were found to be the main causes of death, accounting for 30.00%, followed by placental factors and factors of pregnant women, which accounted for 20.00%, respectively. Placenta factors, umbilical cord factors and factors of pregnant women were the main causes of intrauterine death of fetuses in the third trimester of pregnancy. Therefore, pregnancy tests on time for routine screening is recommended for pregnant women so as to identify the potential risk factors in time and actively carry out symptomatic treatment, thereby reducing the chances of intrauterine death of fetuses and improving the qualities of pregnancy. It is worth clinical attention.
 ...
PMID:Analysis of relevant risk factors for intrauterine death of fetuses in the third trimester of pregnancy. 2841 74


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