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)

Cystine animopeptidase (CAP) and leucine aminopeptidase (LAP) in choriocarcinoma cells grown in culture were assayed and characterized electrophoretically. The specific activity of CAP in choriocarcinoma was about 1.5-fold greater than the specific activity of term placenta. The extract of choriocarcinoma contained an enzyme which is similar to one of the pregnancy-specific serum aminopeptidases in electrophoretic mobility and in resistance to inhibition by 0.1M methionine. The CAP activity was not increased in either the cells or the medium by growing the cells in the presence of oxytocin, estrogen, progesterone, or prostaglandin F-2alpha. It was tentatively concluded that choriocarcinoma cells produce CAP and that it is not regulated by any of these hormones.
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PMID:Cystine animopeptidase and leucine aminopeptidase of choriocarcinoma cells grown in culture. 115 10

Molar pregnancy, which results from an anomaly in the development of the trophoblastic tissue, is now easy to diagnose based on clinical evidence, beta hCG level, and sonography, although it must be histologically confirmed. Treatment remains difficult because of the danger of hemorrhage or trauma during uterine evacuation. Hydatidiform mole was diagnosed in the 1st pregnancy of a 27-year-old woman on the basis of a routine 1st trimester sonogram. Clinical examination revealed a voluminous uterus and a long, closed, very tonic cervix. Sulprostone was administered to aid cervical dilatation. An initial intramuscular injection of sulprostone caused uterine contractions without cervical modifications. 5 hours later an intravenous perfusion of sulprostone was started, during which significant contractions and cervical modifications were observed. An aspiration curettage was performed, in which numerous vesicles typical of the hydatidiform mole were evacuated. There was no need for further cervical dilatation and the curettage was rapid and nonhemorrhagic. The postoperative course was uneventful, and a test of beta hCG levels 6 weeks later was negative. The patient complained of pain during uterine contractions despite use of high doses of pethidine. The frequency of hydatidiform mole varies in different countries. It has been estimated at 1/85 in Indonesia and 1/2000 in the US. The clinical picture of hydatidiform mole includes vomiting often nonresponsive to treatment and metrorrhagia of varying volume, a large uterus for the gestational age, and often bilateral ovarian cysts. A vasculorenal syndrome may also begin at 13-16 weeks of amenorrhea. Beta hCG levels are high for the gestational age. Sonography reveals no embryonic structures. Biopsy shows a complete absence of embryo and amniotic sac. The karyotype is diploid and almost always XX. The mechanism is fertilization of an ovocyte whose nucleus is absent or inactive. The 2 chromosome sets are contributed by the father, a circumstance incompatible with embryonic development. Trophoblastic proliferation occurs without embryonic development. Hydatidiform moles may be transformed to invasive moles or chorioepithelioma. Treatment includes uterine evacuation by aspiration under sonographic control if possible. Many authors recommend oxytocin and antibiotic cover. The use of prostaglandin analogs to facilitate uterine evacuation is controversial, with some authors citing the increased risk of trophoblastic embolism. The mole should be histopathologically and cytogenetically studied, and postmolar follow-up is essential.
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PMID:[Use of sulprostone in the evacuation of molar pregnancies]. 206 88

The number of cases of hydatidiform mole (HM) registered annually in England and Wales has risen since 1973 to 1.54 per 1000 live births in 1983. For women over 50 the risk per pregnancy was 411 times and for girls under 15 it was six times greater than that for women aged 25-29. 7.75% of patients had chemotherapy for invasive mole or choriocarcinoma. Patients who had had oxytocin-induced or prostaglandin-induced uterine evacuation or hysterotomy were more likely to need chemotherapy. Human chorionic gonadotropin (HCG) was undetectable by 56 days after evacuation in 42% of patients, none of whom required chemotherapy; a considerable reduction in follow-up time for this subgroup is proposed. For patients whose HCG values became normal more than 56 days after evacuation and stayed normal for 6 months the risk of recrudescent disease was 1 in 286. In subsequent pregnancies the risk of a second HM was 1 in 76 and that of a third was 1 in 6.5. 11 (0.2%) patients died, 2 from drug-resistant choriocarcinoma.
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PMID:Hydatidiform mole in England and Wales 1973-83. 287 45

Gestational trophoblastic disease cases encountered in 88 pregnant women during a period between January 1985 and June 1992 were retrospectively studied. During the same period we had 6800 deliveries. The incidence of gestational trophoblastic diseases was 12.9 per 1000 deliveries. Of these cases 72 (81.8%) were diagnosed as hydatidiform mole and 16 (18.2%) were diagnosed as choriocarcinoma in histopathological investigations. The preferred method of treatment for cases of hydatidiform mole was termination with suction curettage and oxytocin perfusion. Trophoblastic diseases were common in women with five or more pregnancies from rural areas and our incidence was higher when compared with similar studies. Moreover, our patients had low socio-economic and poor educational status. All these factors seem to be etiologic reasons, besides multiparity.
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PMID:A review of trophoblastic diseases at the medical school of Dicle University. 924 99

An alternatively spliced mRNA coding for a variant estrogen receptor (ER) missing exon 4 (ERdelta4) was detected in the breast tumor cell line MCF7 and meningioma tissue by using the reversed transcriptase PCR technique. The trans-activational properties of this mutant ER were assessed in embryo carcinoma P19EC and human choriocarcinoma JEG3 cells by co-transfection of the ERdelta4 expression vector with an oxytocin promoter construct containing an estrogen-responsive element. ERdelta4 did not trans-activate the oxytocin promoter in either a hormone-dependent or -independent manner. Co-transfection of ERdelta4 together with the wtER did not show any interference of ERdelta4 on the stimulation of the oxytocin promoter by the wtER. ERdelta4 was translated in vitro. Its capacity to bind estradiol, and the binding of the variant to a synthetic estrogen-responsive element were compared to those of the wild-type receptor. ERdelta4 did not bind to a synthetic estrogen-responsive element, nor did it bind estradiol. Hence, ERdelta4 appears to be a silent variant and we speculate that it is without any role in tumor progression.
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PMID:Functional analysis of an alternatively spliced estrogen receptor lacking exon 4 isolated from MCF-7 breast cancer cells and meningioma tissue. 939 58

Despite oxytocin receptors (OTR) being present in human chorio-decidual tissues, their expression and role in placental trophoblast cells in the context of tumor growth or physiological functions related to cell proliferation have never been examined. In the present study we demonstrate the presence and functionality of OTR in normal human trophoblast cell lines (ED77 and ED27) and a choriocarcinoma cell line (BeWo). RT-PCR and immunofluorescence analysis revealed the presence of OTR messenger RNA and protein in these cells. Binding studies using [(125)I]oxytocin ([(125)I]OT) antagonist confirmed the presence of specific binding sites in ED27, ED77, and BeWo cells. OTR functionality was demonstrated by measuring the OT-induced increase in the intracellular calcium concentrations. This effect was dose dependent and was blocked by the selective OT antagonist d(CH(2))(5)[Tyr(Me)(2),Thr(4), Tyr-NH(2)(9)]OVT (OT antagonist). Furthermore, two proteins with apparent molecular masses of 125 and 60 kDa became tyrosine phosphorylated in all of the cell lines after OT stimulation (and an additional protein of 45 kDa in BeWo choriocarcinoma cells), suggesting that this peptide can stimulate tyrosine kinase activity. Finally, we observed a dose-dependent OT stimulation of cell proliferation associated with OTR activation that was completely abolished by the selective OT antagonist. These findings provide the first evidence of the presence of functional OTR in normal trophoblast cell lines as well as in choriocarcinoma cells and show that a specific effect of OT on normal and neoplastic trophoblast is to promote cellular proliferation.
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PMID:Activation of functional oxytocin receptors stimulates cell proliferation in human trophoblast and choriocarcinoma cell lines. 1118 28

Human placental leucine aminopeptidase (P-LAP) plays a major role in the clearance of oxytocin, which is a key hormone in regulating labour pain. To explore the transcriptional regulation of P-LAP gene expression in placenta, we performed systematic studies using human choriocarcinoma cells, BeWo and JEG-3, as a model of placental trophoblastic cells. Transient transfection and luciferase assays using various 5'-deleted P-LAP-luciferase constructs showed that the region from -297 to +49 of the transcription start site was responsible for promoter activity in these cells. Footprinting analysis with nuclear extracts from both cell lines demonstrated at least four sites for nucleoprotein interactions in this region (FP1 to FP4). Site-directed deletion of FP1-4 in luciferase assays indicated the significance of the FP3 region (-214 to -183) for high promoter activity in the cells. Electrophoretic mobility shift assays to identify the proteins interacting with DNA at FP3 revealed three retarded bands, one of which was generated by activator protein-2 (AP-2) binding. Our findings suggest that AP-2 may be one of the important factors regulating P-LAP gene expression in human placenta.
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PMID:Transcriptional regulation of human placental leucine aminopeptidase/oxytocinase gene. 1151 97

In addition to prostaglandins, inflammatory cytokines induce uterine contraction via oxytocin (OT). Placental leucine aminopeptidase (P-LAP), an oxytocinase that is identical to cystine aminopeptidase, destroys OT activity. Patients with spontaneous preterm delivery have higher concentrations of inflammatory cytokines and lower P-LAP activities than those with normal delivery. In addition, the P-LAP promoter region contains putative binding sites for cytokine-induced transcription factors. We therefore postulated that inflammatory cytokines suppress P-LAP expression and examined this notion using BeWo choriocarcinoma cells cultured in the presence of cytokines. However, interleukin-1beta (IL-1beta) increased P-LAP activity in a time- and dose-dependent manner. Furthermore, Western blot analysis showed a dose-dependent increase of P-LAP proteins. We also detected IL-1 type I receptor mRNA in BeWo cells by RT-PCR. Semi-quantitative RT-PCR and Southern blot analysis showed that IL-1beta also increased P-LAP mRNA, which was abrogated by prior exposure to cycloheximide. Luciferase assays did not reveal any regulatory regions that could explain IL-1beta-induced P-LAP mRNA accumulation within 1.1 kb upstream of the P-LAP gene. Immunohistochemical analysis of human placenta with chorioamnionitis demonstrated prominent P-LAP staining at sites of abundant inflammatory cell infiltration. These findings indicated that prolonged exposure to IL-1beta induces P-LAP in the trophoblasts, possibly via other de-novo protein synthesis, which contradicted our initial hypothesis.
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PMID:Interleukin-1beta stimulates placental leucine aminopeptidase/oxytocinase expression in BeWo choriocarcinoma cells. 1256 80

We recently identified two novel aminopeptidases, placental leucine aminopeptidase (P-LAP) and adipocyte-derived leucine aminopeptidase (A-LAP). Enzymatically, P-LAP degrades oxytocin, vasopressin, and angiotensin III, while A-LAP degrades angiotensin II and kallidin. In this study we investigated the expression and localization of P-LAP and A-LAP in human trophoblastic cells in the normal placenta (n = 26), gestational choriocarcinoma (n = 8), and placental site trophoblastic tumor (n = 3). On immunoblot analysis both P-LAP and A-LAP proteins were detected in normal placenta and five choriocarcinoma tissues, as well as in two choriocarcinoma cell lines. Immunohistochemical staining of normal placental tissues demonstrated that P-LAP was not only localized in villous syncytiotrophoblasts but also highly expressed in extravillous trophoblasts (EVTs) invading the decidua or maternal spiral arteries. The expression level of P-LAP on these invasive EVTs reached a maximum during the late first to second trimesters of pregnancy, and it decreased in the third trimester. Similarly, A-LAP was strongly expressed in EVTs invading the decidua or spiral arteries in the second trimester of pregnancy, while it was weakly or moderately expressed in villous cytotrophoblasts or EVTs located in the cell columns. These two aminopeptidases were more strongly expressed in all eight choriocarcinomas and three placental site trophoblastic tumors and mainly localized to the intermediate-type trophoblastic tumor cells invading the uterine myometrium or stromal vessels. In summary P-LAP and A-LAP were predominantly expressed in the invasive phenotype of EVTs during placentation, as well as in the invasive tumor cells of trophoblastic neoplasms. These results suggest the involvement of these aminopeptidases in invasiveness of both normal and malignant intermediate-type trophoblasts possibly through degradation of specific peptide substrates.
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PMID:Expression of placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in human normal and malignant invasive trophoblastic cells. 1469 Dec 98

Placental leucine aminopeptidase (P-LAP), a cystine aminopeptidase that is identical to insulin-regulated membrane aminopeptidase, hydrolyzes oxytocin, which results in the loss of oxytocin activity. We previously isolated genomic clones containing the human P-LAP promoter region, which included two sites homologous to the 10-bp-insulin responsive element (IRE) that was identified on the phosphoenolpyruvate carboxinase gene. We therefore postulated that insulin regulates P-LAP expression via these IREs and investigated this notion using BeWo choriocarcinoma trophoblastic cells cultured in the presence of insulin. Insulin increased P-LAP activity in a time- and dose-dependent manner. Physiological concentrations of insulin at 10(-7) M exhibited the most potent effect on P-LAP activity. Western blotting demonstrated that 10(-7) M insulin increased P-LAP protein levels. Semi-quantitative RT-PCR and Southern blotting showed that insulin also increased P-LAP mRNA, which was abrogated by prior exposure to cycloheximide. Luciferase assay did not reveal any regulatory regions within 1.1 kb upstream of the P-LAP gene that could explain the insulin-induced P-LAP mRNA accumulation. These findings indicate that insulin induces P-LAP expression in trophoblasts, and that it acts via de novo synthesis of other proteins, which partially contradicts our initial hypothesis.
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PMID:Insulin stimulates placental leucine aminopeptidase/oxytocinase/insulin-regulated membrane aminopeptidase expression in BeWo choriocarcinoma cells. 1474 39


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