Prostaglandins and parturition.
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Animals↗
Biomedical subjects
W Gibb
Publications and source records attributed to W Gibb.
Glucocorticoids stimulate prostaglandin H synthase type-2 (PGHS-2) in the fibroblast cells in human amnion cultures.
The human amnion may be an important source of prostaglandins involved in the onset of labour. Glucocorticoids are possible regulators of amnion prostaglandin synthesis and have been shown to stimulate the PGE2 output and prostaglandin H2 synthase (PGHS) activity of human amnion cells maintained in primary monolayer culture. There are two known isoforms of PGHS: the constitutively expressed PGHS-1 and the inducible PGHS-2. Recent studies have shown that the latter isoform is induced by glucocorticoids. The amnion consists of a single layer of epithelial cells beneath which lies a mesenchymal layer containing fibroblasts and it is not known which cell types are responding to glucocorticoids in this manner. In the present study, we demonstrate that although both cell types are present in culture, PGHS-2 protein and mRNA levels increase exclusively within the fibroblasts in response to dexamethasone, while PGHS-1 protein and mRNA levels remain unaffected in both cell types. These results suggest that the stimulation of PGE2 in cultured amnion cells by glucocorticoids is due to an upregulation of PGHS-2 gene transcription in fibroblasts, and that these previously overlooked cells may have important roles to play in the synthesis of prostaglandins involved in labour.
Amnion↗
Localization and developmental changes in prostaglandin H synthase (PGHS) and PGHS messenger ribonucleic acid in ovine placenta throughout gestation.
In numerous animal species, increased prostaglandin output by intrauterine tissues occurs in association with parturition. In the sheep, prostaglandin H synthase (PGHS) is particularly important in regulating this process, and it has been shown recently that the placental content of the inducible form of the enzyme (PGHS-2) increases during the latter part of gestation whereas no change occurs in the constitutive form (PGHS-1). The purpose of the present study was to examine the distribution of cells containing immunoreactive PGHS-2 and PGHS-2 mRNA in the ovine placenta throughout the second half of gestation (80-147 days). Commercially available antisera to PGHS-2 were used for immunohistochemistry with paraffin-embedded tissues, and a 35S-labeled oligonucleotide probe specific for PGHS-2 mRNA was used for in situ hybridization on frozen sections. Immunohistochemistry indicated that there was an increase in the placental content of immunoreactive PGHS-2 after 140 days gestation. At term, the PGHS-2 was located mainly in the uninucleate trophoblast cells in the placentomes. In situ hybridization showed that the distribution of PGHS-2 mRNA was confined to the trophoblasts, with little or no hybridization signal in the maternal endometrium or the maternal syncytium. Autoradiograms of the sections after in situ hybridization were quantified with a computerized image analysis system. There was an increase in the placental content of PGHS-2 mRNA from around 140 days gestation to term, but no change was found in the level of PGHS-1 mRNA. These studies indicate that an increase in the expression of PGHS-2 occurs in the placental trophoblast tissue near parturition in the sheep. The increase in PGHS-2 mRNA is probably responsible for the increase in PGHS-2 protein and PGHS activity that occurs at this time and may contribute to the large increase in prostaglandin production by the ovine placenta at term.
Animals↗
Immunohistochemical localization of the glucocorticoid receptor in human fetal membranes and decidua at term and preterm delivery.
The human fetal membranes and decidua may be important in the onset and/or progression of human labor by providing prostaglandins for this process. Glucocorticoids have been implicated in the regulation of prostaglandin production by these tissues but to date there is no direct evidence for glucocorticoid receptors (GRs) being present in human intrauterine tissues. The purpose of the present study was to determine, using immunohistochemistry, whether the human fetal membranes and decidua contained GRs; to determine the localization of receptors to the cytoplasm or nuclei, and to examine the content and distribution of the GRs in tissues obtained during pregnancy following preterm labor (< 37 weeks) and at term prior to and following term labor. Term tissues were obtained prior to labor by elective Caesarean section (n = 9) or following vaginal delivery (n = 9). Tissues from 14 patients who delivered preterm but with no clinical evidence of infection were also examined. Cryostat sections were thaw-mounted onto microscope slides. The immunoreactive GRs were visualized with an Elite Vectastain ABC Kit using a polyclonal antibody prepared against a synthetic peptide corresponding to amino acids 346-367 of the human GR. At term, nuclear GRs were found in amnion epithelial cells, mesenchyme and the chorion laeve. GRs were present, but were less defined, in the decidua. A similar distribution was found in the preterm tissues. However, nuclear staining in the amnion epithelial cells, mesenchymal cells, chorion and decidua was more pronounced in tissues obtained following preterm labor. This study provides direct evidence for the presence of GRs in human fetal membranes and decidua, and suggests the possible importance of multiple cell types in the action of glucocorticoids in these tissues.
Amnion↗
Localization of prostaglandin H synthase type 2 protein and mRNA in term human fetal membranes and decidua.
Prostaglandin (PG) production by human fetal membranes (amnion and chorion laeve) may be important in the onset and progression of labour, cervical ripening and membrane rupture. Prostaglandin H synthase (PGHS) is a key enzyme in PG formation and has two isoforms, a constitutive form (PGHS-1) and an inducible form (PGHS-2). The present study examined the cellular distribution of the PGHS-2 enzyme and PGHS-2 mRNA in term human fetal membranes and decidua prior to and following labour, using immunohistochemistry and in situ hybridization with an 35S-labelled oligonucleotide probe. The PGHS-2 protein was found to be localized in amnion epithelial cells and chorion laeve trophoblast, but was absent or at low levels in the decidual stroma in most tissues, although cells surrounding some of the blood vessels in the decidual did express PGHS-2. In situ hybridization demonstrated that PGHS-2 mRNA had a similar distribution and was localized to amnion epithelial cells, cells in the amnion-chorion mesenchyme, chorion laeve trophoblast and, occasionally, to cells surrounding blood vessels in the decidua. Of particular note was the high mRNA expression in some cells and low expression in other cells, particularly in the chorion, and the low level of PGHS-2 mRNA in decidua. There was no observable difference in the cellular localization of PGHS-2 protein or PGHS-2 mRNA in tissues obtained prior to and following labour. The studies indicate that, at term, the inducible form of PGHS, PGHS-2, is expressed at a high level in fetal tissues in a number of different cell types rather than in the maternal decidua.
Base Sequence↗
Aprotinin in children undergoing repair of congenital heart defects.
BACKGROUND: Aprotinin use in adults is increasing, and its use in children has recently been reported. METHODS: The efficacy of aprotinin in children was tested in 80 children. Patients were in four groups: reoperations (59), neonates (8), extremely cyanotic children (6), and other complex repairs (7). The results were compared with those of 55 control infants and children: reoperations (25), neonates (10), cyanotic (10) and complex (10). Treatment groups were identical in age, sex ratio, cross-clamp time, and bypass time. RESULTS: Patients treated with aprotinin had a significant reduction in chest tube drainage (16.5 +/- 9.8 versus 33.4 +/- 22.1 mL.kg-1.h-1; p < 0.001) and time to skin closure (64.2 +/- 23.7 versus 80.1 +/- 24.6 minutes; p < 0.001). Transfusion requirements were decreased in aprotinin-treated patients 4.2 +/- 3.4 versus 6.7 +/- 5.2 donors; p < 0.001). All of the control patients were exposed to at least one donor, whereas 10/80 (12.5%) of the aprotinin-treated group had no blood use (p < 0.006). There were no cases of renal insufficiency or allergic reactions in children receiving aprotinin. Three patients had thrombotic episodes: 2 superior vena caval problems and a lower extremity deep venous thrombosis. There were 3 cases of mediastinitis in the aprotinin group versus none in control patients (p < 0.05). CONCLUSIONS: We conclude aprotinin is an effective means of reducing bleeding, operating time, and donor exposure in infants and children. An increased rate of thrombosis and possibly mediastinitis are potential problems.
Aprotinin↗
Influence of culture media on prostaglandin output by dispersed amnion cells.
The purpose of the study was to examine the influence of culture media on prostaglandin (PG) production by amnion cells and their response to phospholipase A2. Cells were dispersed from term tissue obtained by elective C-section; the PGE2 output was studied during the first 24 h of culture. The basal PGE2 production from cells cultured in Media 199 (M199) supplemented by 10% horse serum (HS) was significantly greater than that of cells cultured in F12:DME supplemented by 10% fetal calf serum (FCS). Furthermore, phospholipase A2 stimulated PGE2 production in cells cultured with M199 + HS but had no influence on PGE2 output by cells cultured with F12:DME + FCS. This effect was dependent on the presence of HS. The factor(s) in HS responsible was not removed by heating at 56 degrees C for 3 min, treatment with dextran coated charcoal or by ultrafiltration through 10,000 MW filters. Thus, culture media alters the in vitro production of PG and response to phospholipase A2 by amnion cells.
Amnion↗
Studies on the action of interleukin-1 on term human fetal membranes and decidua.
Recent studies have indicated the possible importance of cytokines in the onset of term and preterm labor. To examine this further, the effect of interleukin-1 beta (IL-1 beta), interleukin-1 alpha (IL-1 alpha), and interleukin-6 (IL-6) on prostaglandin output by dispersed cells from human amnion, chorion laeve, and decidua obtained at term (38-40 weeks gestation) was examined. During the first or second 24 h of culture no significant effect of these interleukins on prostaglandin output was observed. The reason for this apparent refractoriness was further investigated by studying the distribution of IL-1 receptors in frozen sections of undisrupted fetal membranes and decidua at term. Whole-tissue autoradiography indicated that receptors were present in chorion-decidua but not in amnion. By using emulsion autoradiography, IL-1 receptors were found in high concentrations in chorion laeve and were absent in amnion and at low levels in the decidua. These studies indicate that under normal circumstances in human pregnancy at term IL-1 did not stimulate prostaglandin production by dispersed cells. In the case of amnion, this may be due to the absence of receptors, and therefore it would appear that the IL-1 receptor must first be induced in this tissue before it can respond to this cytokine. Furthermore, although chorion laeve expresses the IL-1 receptor, dispersed cells from this tissue did not respond to the cytokine by increasing prostaglandin output.
Amnion↗
Studies on the action of dexamethasone on prostaglandin production by freshly dispersed amnion cells.
The human amnion may be an important source of prostaglandins (PGs) during pregnancy and possibly labor. Glucocorticoids stimulate PG production in confluent amnion cell cultures, but in freshly dispersed cells they inhibit PG production. The purpose of the present study was to determine if this inhibitory effect occurred at the level of arachidonic acid release from lipids. Cells were labeled with radioactive arachidonate and the release of radioactivity was measured in the presence or absence of dexamethasone. No significant effect of dexamethasone treatment was observed. The possibility that glucocorticoid treatment inhibited the release of arachidonate from a specific species of phospholipid was also examined. However, no difference was found in the distribution of arachidonate between lipids isolated from glucocorticoid-treated and untreated cells. Furthermore, dexamethasone treatment did not alter the lipocortin 1 and 2 content of dispersed cells, determined following sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. These studies indicate that the inhibition of prostaglandin production by dispersed amnion cells by glucocorticoids most likely occurs at a point distal to arachidonic acid release.
Amnion↗
Prostaglandin production by porcine allantochorion in vitro: effect of cortisol infusion in vivo.
The effect of cortisol infusion into the porcine fetus on subsequent prostaglandin (PG) production in vitro by the fetal placenta (the allantochorion) was studied. Also, the possible in vitro effects of glucocorticoids and other steroids on PG production by dispersed cells were examined. Two fetuses in each of 6 sows were catheterized on day 100 or 101 of gestation (normal gestation is 114-116 days); one was infused with cortisol (6 mg/day) and one with saline for 5 days beginning on day 103. On day 108, fetal allantochorionic tissue was aseptically collected from the infused fetuses and 2 uninfused litter mates (controls). Pieces of tissues were cut from the allantochorion (4 sows) and dispersed cell preparations were made from each fetus (4 sows). Each preparation was cultured for 24 h, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha (prostacyclin metabolite) measured. In vivo cortisol infusion had no significant effect on the in vitro production of PGE2 or PGF2 alpha by tissues or dispersed cell preparations. However, tissue from the fetuses infused with cortisol produced significantly less 6-keto-PGF1 alpha than uninfused controls (54% of control, p < 0.05). The dispersed cells from uninfused fetuses and 2 cortisol-infused animals were also incubated for 24 h with 10(-7) and 10(-9) M concentrations of estrone, estradiol, progesterone, cortisol, and dexamethasone, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha was measured. No significant effect of any of these steroids in vitro on prostanoid production was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Ketoprostaglandin F1 alpha↗
Effect of smoking on fibronectin production by human amnion and placenta.
Fibronectin production from amnion and placental tissues was evaluated in pregnant woman smokers and nonsmokers in order to examine if there were alterations of fibronectin metabolism in intrauterine tissues. In both amnion and placental tissues, cycloheximide inhibited the fibronectin output indicating that it was being synthesized. Mean fibronectin output by amnion in pregnant woman smokers was significantly lower than that in pregnant woman nonsmokers. In contrast, in the placenta from pregnant woman smokers, the output was significantly higher than that in pregnant woman nonsmokers. The present observations indicate that smoking alters an important biochemical constituent in amnion and placenta, possible leading to some complications.
Amnion↗
Amnion cell prostaglandin E2 stimulatory activity in chorion laeve-conditioned medium.
In this study we demonstrate the presence of a stimulant(s) to amnion cell prostaglandin (PG) E2 production in chorion-conditioned medium (CCM). The CCM induced a dose-dependent increase in amnion cell PGE2 production. This stimulatory activity was eliminated by heat and protease treatment. Maximal stimulation of amnion PGE2 by CCM did not occur until after 2 h of incubation, and treatment with cycloheximide (1 microgram/ml) effectively eliminated the ability of the amnion cells to respond to CCM. Additionally, CCM and arachidonic acid (2-40 microM) were synergistic in their stimulatory actions on amnion PGE2 production. CCM-treated amnion cells recover more quickly from acetylsalicylic acid pretreatment as compared to control. It is concluded that CCM contains a heat-labile protein which stimulates amnion cell PGE2 production by induction of prostaglandin endoperoxide synthase activity.
Amnion↗
Influence of calcitriol on prolactin and prostaglandin production by human decidua.
Receptors for calcitriol are described in human decidua. They exhibit a dissociation constant of 35 +/- 6 pM and they are at concentrations similar to those found in other tissues (0.45 +/- 0.04 fmol/micrograms DNA). They are highly specific for calcitriol since neither of the other vitamin D3 derivatives nor the steroid hormone tested displaced labeled calcitriol from the receptor. Also, calcitriol at concentrations of 10(-13) to 10(-11) M stimulates prolactin secretion by dispersed decidual cells. At these concentrations, however, the hormone has no effect on prostaglandin production. The specificity of calcitriol action was further examined by studying the effect of estrogen, progesterone, testosterone, dexamethasone and cortisol, all at 10(-7) M, on the secretion of prolactin and prostaglandins. Under the conditions used in this study, the steroids have no effect on prolactin secretion; but dexamethasone significantly inhibits prostaglandin F2 alpha output by the cells. Taken together with previous studies from our laboratory demonstrating that decidua can synthesize calcitriol the present study indicates that this hormone has an autocrine effect on human decidual cells.
Binding, Competitive↗
Effects of glucocorticoids on prostaglandin formation by human amnion.
The human amnion may be an important source of prostaglandins involved in the onset of human labor and therefore it is important to define the factors that regulate their formation in this tissue. In the present study we demonstrate that glucocorticoids inhibit prostaglandin production by freshly isolated amnion cells. The inhibitory action of the glucocorticoids, however, changes to a stimulatory action when the cells are maintained in primary culture for a few days. For both inhibition and stimulation, concentrations of 10(-8) M dexamethasone or greater were required to give significant effects, and estradiol and progesterone had no effect on the prostaglandin output of the cells. Epidermal growth factor (EGF), which has previously been found to stimulate prostaglandin output by confluent amnion cells, did not alter prostaglandin output of cells initially placed in culture. Furthermore, the stimulatory action of EGF and dexamethasone appeared additive. The calcium ionophore A23187 stimulated prostaglandin output in freshly isolated cells and accentuated the inhibitory effect of dexamethasone. These studies indicate that prostaglandin formation by human amnion during pregnancy could be regulated by glucocorticoids. These steroids are easily available to the amnion by way of cortisone conversion to cortisol by the maternal decidua. The results also indicate that amnion is capable of responding to glucocorticoids in both a stimulatory and inhibitory fashion and whether one or both actions are of importance in vivo is a question that is as yet unresolved.
Amnion↗
A case of progressive subcortical gliosis presenting clinically as Steele-Richardson-Olszewski syndrome.
A patient presenting with the characteristic clinical features of Steele-Richardson-Olszewski syndrome is described, in whom neuropathological examination revealed atypical features, including extensive cortical and subcortical gliosis. The clinical and pathological features are discussed with particular reference to Creutzfeldt-Jacob disease and it is proposed that the case should be classified as progressive subcortical gliosis.
Astrocytes↗
Cyclooxygenase products formed by primary cultures of cells from human chorion laeve: influence of steroids.
Cells were isolated from human chorion laeve obtained at term (38-40 weeks gestation) by elective caesarean section and were maintained in primary culture for 1 week in defined media supplemented with 10% fetal calf serum. The production of various cyclooxygenase products by the cultures was examined. Little or no prostaglandin (PG) F2 alpha, 6-keto-PGF1 alpha, thromboxane B2, or 13,14-dihydro-15-keto-PGF2 alpha was found. In contrast, the cells produced PGE2 which was low on day 0, increased during culture to a maximum on day 1 or 2, then declined to low levels. When cells were grown in the presence of media containing cortisol, dexamethasone, progesterone, and estradiol (at 10(-7) or 10(-9) M), the glucocorticoids (at 10(-7) and 10(-9) M), but not estrogen or progesterone, markedly inhibited the increase in PGE2 output. There was no difference in the protein content and thymidine incorporation of cells grown in the presence of glucocorticoids when compared with controls. This inhibitory effect was not sensitive to cycloheximide (1 microgram/mL) indicating protein synthesis may not be involved in the process. These studies indicate that PGE2 is the major prostaglandin formed by primary cultures of chorion laeve and that prostaglandin metabolism in the chorion is sensitive to glucocorticoid inhibition.
Cells, Cultured↗
Comparison of the specific binding of cortisol in human amnion, amniotic fluid, and plasma.
The purpose of this study was to compare the specific cortisol-binding protein found associated with human amnion with specific cortisol binding in human amniotic fluid and plasma. The electrophoretic mobility on polyacrylamide gels of the specific cortisol binding in amnion, amniotic fluid, and maternal plasma was identical. The influence of pH on cortisol binding activity was similar in all tissues and the cortisol binding was immunoprecipitable by a polyclonal antibody raised against human corticosteroid-binding globulin. The interaction of the cortisol binding protein with concanavalin A was studied in preterm amniotic fluid, term amniotic fluid, term amnion, and plasma from pregnant women at term and women under oral contraceptive treatment. Binding to concanavalin A was similar in term amnion and term amniotic fluid but was less than that found with both preterm amniotic fluid and term plasma. These results indicate that the cortisol binding protein associated with human amnion has similar characteristics to plasma corticosteroid-binding globulin, but that its state of glycosylation appears to be more like that of the cortisol binding protein in term amniotic fluid rather than in plasma.
Amnion↗
Effect of catecholamines on porcine Sertoli and Leydig cells in primary culture.
The accumulation by purified immature porcine Leydig and Sertoli cells of cyclic adenosine 3',5'-monophosphate in the presence of 1-methyl-3-isobuthylxathine was studied and their respective testosterone and 17 beta-estradiol production in response to catecholamines was assessed in vitro. These substances increased both basal and FSH-stimulated cyclic adenosine 3',5'-monophosphate accumulation in Sertoli cells. In contrast, catecholamines slightly enhanced basal cyclic adenosine 3',5'-monophosphate production but inhibited its human chorionic gonadotropin-stimulated accumulation by Leydig cells. Catecholamines had no effect on basal and stimulated testosterone release by these cells, while dopamine inhibited 17 beta-estradiol synthesis by Sertoli cells. Using various alpha- and beta-adrenergic agonists and antagonists, beta-receptors, likely of the beta 1-subtype, were shown to be present in both cell lines. Taken together these data suggest the presence of a cyclic adenosine 3',5'-monophosphate-linked adrenergic receptor in porcine Leydig and Sertoli cells, the role of which remains to be determined.
1-Methyl-3-isobutylxanthine↗