Mechanisms of human parturition: role of prostaglandins and related compounds.
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Arachidonic Acids↗
Biomedical subjects
M D Mitchell
Publications and source records attributed to M D Mitchell.
Prostanoids in rabbit aqueous humor: effect of laser photocoagulation of the iris.
The authors measured concentrations of prostanoids (prostaglandin-like substances) in aqueous humor from normal pigmented rabbit eyes and from those subjected to argon laser photocoagulation of the iris. The predominant prostanoids quantitatively were prostaglandin E2 (PGE2), PGF2 alpha, and PGD2 with minor amounts of 6-keto-PGF1 alpha and thromboxane B2. In all cases, concentrations of prostanoids in laser-treated eyes were substantially greater than those in normal eyes. This finding was particularly striking in the case of PGE2 which increased 60-fold from 87 pg/ml to 5.5 ng/ml after irradiation. Concentrations of prostanoids following photocoagulation were related to the number of administered laser lesions and prostanoid release was associated with an initial hypertensive response and disruption of the blood-aqueous barrier.
Animals↗
Plasma prostaglandins during the intravenous infusion of angiotensin II in pregnant women.
The possible relation between prostaglandin production and the sensitivity of pregnant women with pregnancy-induced hypertension to the pressor effects of angiotensin II was investigated. Plasma prostaglandin levels were determined in four groups of women before, during, and after intravenous infusion of angiotensin II. Concentrations of the stable metabolites of prostaglandin E2, prostaglandin F2 alpha, and prostaglandin I2 (prostacyclin) were quantified by specific radioimmunoassays in the plasma of nonpregnant women, women pregnant in the late third trimester, and women pregnant in the late third trimester with either pregnancy-induced or chronic hypertension. Plasma prostaglandin concentrations did not change significantly during angiotensin II infusion in any of the four groups of women. Levels of the prostacyclin metabolite, however, were significantly higher in the hypertensive pregnant women than in the normotensive pregnant women.
6-Ketoprostaglandin F1 alpha↗
Effect of fetal intravascular 4-aminoantipyrine infusions on myometrial activity (contractures) at 125 to 143 days' gestation in the pregnant sheep.
Myometrial activity of low amplitude and long duration--contractures--is present throughout gestation in the pregnant ewe and other species. This activity differs from the contractions of labor and delivery. Between 125 and 143 days' gestation, 4-aminoantipyrine infused into the fetus at rates that produced maternal uterine vein plasma concentrations of 4-aminoantipyrine of 5.95 +/- 1.23 (mean +/- SEM, n = 5) mg X 100 ml-1 markedly depressed both total myometrial electromyographic activity to 28.6% and frequency of contractures to 30.5% of preinfusion values. By 60 minutes of infusion, maternal uterine vein plasma 13,14-dihydro-15-keto prostaglandin F2 alpha concentration was reduced to 14% of the resting level. Two conclusions were drawn from this study. First, prostaglandins are involved in the regulation of contractures. Second, when infusions of 4-aminoantipyrine are used to quantify uterine or umbilical blood flow, the possibility exists that changes will occur in physiologic systems that are modified by prostaglandins.
Ampyrone↗
Maintenance and characterization of human myometrial smooth muscle cells in monolayer culture.
Human myometrial cells were dispersed from uterine tissue by limited enzymatic digestion of myometrium that was obtained at the time of hysterectomy. The dispersed myometrial cells that are obtained in this manner can be maintained in monolayer culture in the presence of medium that contains fetal bovine serum. In primary culture, as well as after passage, the characteristics of these cells are morphologically and biochemically similar to those of smooth muscle cells and myometrial tissue.
Cells, Cultured↗
Characterization of prostaglandin formation by human amnion cells in monolayer culture.
In the present investigation, we found that among the prostanoids that human amnion cells, which are maintained in monolayer culture, secrete into the culture medium, prostaglandin E2 is by far the predominant one. In the presence of inhibitors of prostaglandin synthase, the production of prostaglandin E2 by these cells is abolished. Amnion cells maintained in the presence of fetal calf serum produce greater quantities of prostaglandin E2 than do cells maintained in serumless medium. In the amnion cells, there is little or no metabolism of prostaglandin E2; this also is true of amnion tissue. The unique characteristics of prostaglandin biosynthesis and metabolism by human amnion cells in monolayer culture are identical with those of human amnion tissue. Hence, we suggest that amnion cells in culture constitute an excellent model for investigations of the regulation of prostaglandin E2 biosynthesis in this tissue.
Amnion↗
Stimulation of prostaglandin E2 synthesis in human amnion cells maintained in monolayer culture by a substance(s) in amniotic fluid.
A substance(s) in amniotic fluid of human pregnancies promotes a striking increase in prostaglandin E2 production in human amnion cells maintained in primary monolayer culture. The prostaglandin E2 synthesis-stimulatory factor(s) acts in a time- and dose-dependent manner to accelerate prostaglandin E2 formation. We suggest that a substance of fetal origin enters amniotic fluid by way of fetal urine and acts to regulate prostaglandin E2 synthesis in amnion. Such a process may be of fundamental importance in the regulation of amniotic fluid volume homeostasis and in the initiation of parturition.
Amnion↗
Prostaglandin synthase inhibitory activity in the plasma of rhesus monkeys during late pregnancy: effect of dexamethasone.
Plasma from rhesus monkeys during late pregnancy contained a factor(s) that was inhibitory of prostaglandin synthase activity. There was no consistent trend in the inhibitory activity of plasma obtained between 120 days of gestation and term (approximately 167 days of gestation). Administration of dexamethasone (0.125 to 1.0 mg twice daily) consistently increased inhibitory activity in plasma after an initial treatment period of 5-10 days. Administration of dexamethasone for several weeks is associated with prolongation of gestation in rhesus monkeys. We suggest that the action of dexamethasone, to delay parturition is related, in part, to an enhancement of the activity of a circulating factor(s) that is inhibitory of prostaglandin synthase activity.
Animals↗
Effect of radiation on prostaglandin production by human bowel in vitro.
The effect of gamma irradiation on the production of prostaglandins by human colon was investigated. Squares of tissue in organ culture dishes were irradiated with 500, 1000, or 2500 rad in single applications. Tissues that were not irradiated served as controls. After treatment the tissues were superfused and prostaglandin concentrations in the effluent fluid were determined. The rates of production of prostaglandins E2 and F2 alpha by irradiated tissues were significantly lower (p less than 0.05) than those of nonirradiated tissues. Neither the release of lactate dehydrogenase nor the rate of production of 13,14-dihydro-15-keto-prostaglandin F2 alpha were increased in the irradiated samples, suggesting that neither decreased cell viability nor increased prostaglandin metabolism accounted for the decreased prostaglandin production rates. We conclude that irradiation of the human colon in vitro results in an acute inhibition of prostaglandin synthesis. The cytoprotective nature of prostaglandins is discussed with regard to the possible pathophysiological significance of these findings.
6-Ketoprostaglandin F1 alpha↗
Fall in blood pressure in response to volume expansion in pregnancy-associated hypertension (pre-eclampsia): why does it occur?
The infusion of 500 ml of a volume expanding solution caused a significant fall in blood pressure for up to 72 h in 35 women with pregnancy-associated hypertension of varying grades of severity. The response to the infusion was not obviously related to the clinical severity of the underlying disorder, nor to the extent of plasma volume expansion produced. The plasma volume of oedematous women increased, while there was no significant change in non-oedematous women in response to the infusion. Changes in other measurements were similar in oedematous and non-oedematous women. There was no evidence for prostacyclin release into the circulation in response to the infusion as a mediator of the blood pressure response. Both 6-keto-prostaglandin F1 alpha levels and 13,14-dihydro-15-keto-prostaglandin F (PGFM) levels fell significantly, suggesting suppression of prostaglandin release by the infusion. The antihypertensive effect of volume expanders in pregnancy-associated hypertension is mediated by a factor other than simple volume expansion.
Adult↗
The influence of spontaneous and induced labour on the rise in prostaglandins at amniotomy.
Maternal peripheral plasma levels of 13,14-dihydro-15-keto-prostaglandin F (PGFM) were measured immediately before and 5 min after amniotomy. Three groups of women were studied: women in late pregnancy; women in spontaneous labour; and women who had received intravaginal prostaglandin E2 (PGE2) pessary. There was no significant difference in the magnitude of the rise in PGFM after amniotomy in late pregnancy or during spontaneous labour suggesting that labour has no influence on the release of prostaglandin F2 alpha (PGF2 alpha) induced by artificial rupture of the fetal membranes. However, local administration of PGE2 before amniotomy caused a greater rise in PGFM suggesting that PGE2 can influence the release and/or metabolism of PGF2 alpha.
Adult↗
Maternal plasma inhibition of prostaglandin synthase during human pregnancy, parturition and the puerperium.
To study the possibility that circulating endogenous inhibitor(s) of prostaglandin synthesis (EIPS) represent a control mechanism for prostaglandin production during human pregnancy and parturition, we have measured maternal plasma EIPS levels serially during pregnancy, labour and the puerperium, and cross-sectionally during the course of labour. No significant trends were detected in relation to pregnancy or parturition. These results do not support a role for maternal plasma EIPS in the control of prostaglandin production during human pregnancy or labour.
Cyclooxygenase Inhibitors↗
Ontogeny and neonatology of circulating endogenous inhibitor(s) of prostaglandin synthase in the human.
To further understand the mechanism by which in vivo prostaglandin synthesis may be orchestrated, plasma levels of endogenous inhibitor(s) of prostaglandin synthase (EIPS) in the human fetus, neonate and adult have been measured. In general, a reciprocal relationship was found between plasma EIPS levels and previously reported plasma prostaglandin concentrations. This result supports a role for EIPS in the control of prostaglandin biosynthesis in the human.
Adult↗
ACTH control of steroid secretion from adrenal cells of the developing rhesus monkey (Macaca mulatta).
Cells from adrenal glands of 140-160 days foetal, neonatal and infant Rhesus monkeys (Macaca mulatta) were prepared, by collagenase digestion and incubated with 10 pg-16 ng/ml ACTH. The production of cortisol, androstenedione, corticosterone, progesterone and prostaglandins was measured. The cortisol production in the 140 day and 160 day foetuses and in the neonatal adrenal cells was comparable. It was 2-fold higher in adrenal cells of 6 month infant monkeys. In all the groups there was an increasing production of cortisol with increasing ACTH concentration, and a response to low physiological concentrations of ACTH. The androstenedione production was significantly greater in the 160 day foetuses than in either those of 140 days or of the neonate which demonstrated a poor response to increasing ACTH concentrations. It responded well to increasing ACTH in adrenal cells from 6 month infant monkeys. Corticosterone output was 1/10th of cortisol with only the 140 day foetuses showing an increase in production with increasing ACTH concentrations. The results demonstrate that cells of the primate foetal adrenal gland are not inherently unresponsive to ACTH stimulation as regards cortisol production, which per/micrograms DNA does not appear to change over the last 25 days before term.
Adrenal Cortex Hormones↗
The role of prostaglandins in Bartter's syndrome.
In two children with Bartter's syndrome, treatment with indomethacin halved the urinary excretion of prostaglandins E and F within 24 hours and subsequently maintained it within the normal range during follow-up for more than 5 years. Growth rate was improved and plasma renin and aldosterone and the urinary excretions of sodium and calcium fell to normal. Both children continued to lose excessive quantities of potassium in the urine. The results provide further evidence that over-production of prostaglandins is not the primary cause of Bartter's syndrome.
Aldosterone↗
The mechanism(s) of human parturition.
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Amniotic Fluid↗
Prostaglandin synthase inhibitory activity in plasma of women with dysmenorrhea.
Prostaglandins have been implicated in the etiology of dysmenorrhea, and plasma levels of prostaglandin F metabolite are increased in women during dysmenorrhea episodes. We determined the prostaglandin synthase inhibitory activity of plasma obtained from the blood of women who experience moderate to severe dysmenorrhea. Blood was obtained at the onset of dysmenorrhea ("symptomatic") and during the late follicular phase of the ovarian cycle ("asymptomatic"). Prostaglandin synthase inhibitory activity in all samples was comparable to that previously found in adult women, and we found no difference in activity between the paired plasma samples, those obtained during symptomatic and asymptomatic times. Protein denaturation of the plasma by boiling also did not produce differences in prostaglandin synthase inhibition.
Adult↗
Origin of prostanoids in human amniotic fluid: the fetal kidney as a source of amniotic fluid prostanoids.
The present study was designed to investigate the origin of prostanoids that are present in amniotic fluid. We evaluated the concentration of prostaglandins in fetal urine that was obtained from newborn infants immediately after delivery either before or after the onset of spontaneous labor or after oxytocin-induced labor. We found that the levels of prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha, and 13, 14-dihydro-15-keto-PGF2 alpha in the fetal urine of newborn infants delivered after the spontaneous onset of labor and after oxytocin-induced labor were significantly greater than the levels in the fetal urine of newborn infants delivered before the spontaneous onset of labor. We conclude that one source of the prostanoids present in amniotic fluid is fetal urine, and, thence, fetal kidneys, and that labor, whether spontaneous or induced, caused increased excretion of prostanoids in fetal urine.
Amniotic Fluid↗