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A R Fuchs

Publications and source records attributed to A R Fuchs.

At least 91 records · Page 5Linked to original sources

Oxytocin and the initiation of human parturition. I. Prostaglandin release during induction of labor by oxytocin.

Concentrations of plasma prostaglandins E and F and the 15-keto-13,14 dihydrometabolite of PGF2 alpha (PGFM) were determined by radioimmunoassay in 15 women who underwent induction of labor with oxytocin. Plasma PGFM rose significantly during the oxytocin infusion in nine women who went on to deliver vaginally but did not change in six women in whom induction of labor failed. Plasma PGE and PGF levels also rose during the infusion in the nine women with successful induction of labor but the changes were not statistically significant. In comparison to the six women in whom induction failed, however, plasma PGE in the nine women with successful induction reached significantly higher levels. Oxytocin infusions elicited uterine contractions of similar frequency in both groups of women, but the cervix failed to dilate in the six women in whom induction failed. The oxytocin-induced rise in plasma PGFM is, therefore, not simply a consequence of uterine contractions. We suggest that oxytocin stimulates PGF production in the pregnant uterus when it is appropriately sensitized to oxytocin, causing a potentiation of the oxytocin-induced contractions which is necessary for the contractions to become efficient in dilating the cervix. We further suggest that the stimulation of PGF production by oxytocin is mediated by oxytocin receptors, probably in the decidua.

Dinoprost↗

Oxytocin and the initiation of human parturition. II. Stimulation of prostaglandin production in human decidua by oxytocin.

In the present study we have investigated the effect of oxytocin on the production of prostaglandins E and F (PGE and PGF) by human decidua, amnion, and myometrium in vitro. We found that oxytocin causes a significant increase in the production of both PGE and PGF in the decidua and in the production of PGE in the amnion. In the myometrium the stimulatory effect of oxytocin on PGF production was small and not statistically significant, and PGE production was not affected at all. On the basis of these results, we propose that oxytocin provides the stimulus for the accelerated prostaglandin production in decidua and fetal membranes at the onset of labor. Since oxytocin levels rise in the fetal circulation at this time, the oxytocin stimulus may be of fetal origin as well as of maternal origin.

Decidua↗

Effects of mating on levels of oxytocin and prolactin in the plasma of male and female rabbits.

The effects of mating on plasma levels of oxytocin and prolactin in male and females rabbits have been investigated. Blood was collected through indwelling cardiac catheters at intervals of 1, 2, 4, 6, 12, 24, 36 and 60 min after mating. In female rabbits additional samples were taken 5h after mating, as well as daily during the ensuing pregnancy or pseudopregnancy. They were also fitted with intrauterine balloons for recording uterine activity. Copulation induced a rapid, transient rise in plasma oxytocin in female rabbits at the same time as a fall in plasma prolactin. Mating or sexual excitement had no significant effect on plasma concentrations of oxytocin or prolactin in bucks. Relatively large fluctuations of plasma oxytocin were seen in male rabbits under normal conditions and after mating, suggesting episodic release of oxytocin in a random fashion. The uterine recordings indicated that, in spite of the modest release of oxytocin, a strong sympathetic adrenal activation occurred in response to mating and this provided the overriding influence on uterine activity. During pregnancy plasma levels of prolactin rose significantly on day 4, and remained raised throughout most of gestation. Plasma prolactin fluctuated widely during the first half of pregnancy but the mean levels were higher than those found during the second half of gestation. When pseudopregnancy was induced with injection of an ovulating dose of LH, plasma prolactin rose in a similar manner as during early gestation or mating-induced pseudopregnancy. Thus, in contrast to rats, stimuli associated with mating have no direct influence on the subsequent release of prolactin in rabbits. The secretion of prolactin during gestation seems to be controlled entirely by ovarian steroids, probably progesterone.

Animals↗

Oxytocin release and uterine activation during parturition iin rabbits.

Plasma oxytocin was measured by a specific RIA in blood of pregnant and parturient rabbits obtained through an indwelling cardiac catheter. Uterine activity was continuously recorded by means of indwelling intrauterine balloons. Plasma oxytocin concentrations were low throughout gestation (mean +/- SE, 16.1 +/- 2.0 pg/ml), with no rise toward term. During parturition, a significant increase in plasma oxytocin was observed in all but 3 of 21 rabbits studied. Plasma oxytocin rose rapidly and reached high levels within minutes of the beginning of labor contractions. The mean concentration was 193 +/- 55 pg/ml (SE) 30--60 sec before the expulsive phase. The highest oxytocin concentrations were usually observed at the delivery of the first fetus (mean, 258 +/- 89 pg/ml); this was followed by a rapid decline. Baseline levels were reached in 20--60 min. Uterine activity during parturition was well correlated with plasma oxytocin; an abrupt increase was observed a few minutes (5.1 +/- 1.2 min) before the expulsion of the young, followed by a gradual disappearance over 30--70 min. Little or no circulating oxytocin was detected during delivery in 3 rabbits. In these, the course of parturition was abnormal and protracted, resulting in a high percentage of stillborn young. The series of strong contractions associated with normal delivery was absent. By contrast, abortion in 2 rabbits was associated with elevated plasma oxytocin levels and increased uterine activity. These findings indicate that a substantial amount of oxytocin is released into the circulation during delivery and suggest that the normal activation of the uterus at parturition depends on oxytocin. The stimulus eliciting the release of oxytocin is not known. Dilatation of the birth canal by the passage of a fetus was not consistently followed by detectable oxytocin release, and during delivery, a second release of oxytocin was often unrelated to any apparent stimulus. Intact spinal cord caudal to T5 does not appear to be essential for the release of oxytocin at parturition, since spinal transsection in 2 rabbits was associated with normal oxytocin release at delivery. Injections of synthetic oxytocin caused a dose-dependent increase in plasma oxytocin and uterine activity. Disappearance of oxytocin from the circulation followed a double exponential curve; the mean half-life of the initial rapid phase was 1.82 min after single injections and the half-life of the low component was 26.5 min. The initial volume of distribution was close to the volume of the vascular compartment, and the total apparent volume of distribution was about twice the size of the extracellular compartment. After constant infusions, a half-life of 3.6 min was obtained for the uncorrected values during the initial phase.

Animals↗

PGF2 alpha regulation of LH action on testicular testosterone production.

PGF2 alpha has a reversible inhibitory effect on testicular T production in vitro and in vivo, while PGE2 is without effect. The PGF2 alpha effect is overcome by LH in a dose-dependent manner. Anti-LH has a similar effect as PGF2 alpha, the effects of both substances are not additive. Suppression of endogenous PG biosynthesis leads to potentiation of LH-stimulated T production in vitro but is without effect on basal T output. We conclude that PGF2 alpha inhibits testicular testosterone production by interfering with LH action on the Leydig cells. Histochemical studies indicate that PG synthesis in testes occurs mainly in the interstitial cells (4) and is probably androgen-dependent (5). Endogenous PGF2 alpha may therefore have a role in a local negative feedback regulation of LH action in testicular tissue.

Animals↗

Electrical and mechanical activity of rat uterus in vivo during the estrous cycle.

Electromyograms were obtained from three different locations on the uterus of conscious, unrestrained rats during the 4 day estrous cycle. Intrauterine pressure changes were monitored simultaneously by means of indwelling intraluminal balloons (vol. 0.02 to 0.05 ml.). Electrical activity consisted of bursts of action potentials that were usually initiated at either end of the uterus. Propagated burst activity gave rise to cyclic intrauterine pressure changes, whereas bursts appearing at one electrode only did not elicit any measurable contractions. The rate of intrauterine pressure development depended on the propagation velocity, whereas the tension achieved was related to the duration of burst activity. All three parameters of electrical activity studied, namely, the duration and frequency of spike bursts, as well as their rate of propagation, varied significantly during the cycle. Regional differences were also subject to cyclic variations; thus, in proestrus the bursts originated predominantly at the cervical end, whereas in diestrus they were usually initiated at the ovarian end. Oxytocin stimulated the frequency and duration of bursts along the whole uterus and elicited corresponding changes in intrauterine pressure. Response to oxytocin was dose dependent and modified by cycle stage. Norepinephrine caused a transient prolongation of burst activity that was not dose dependent; epinephrine had a marked dose-dependent inhibitory action. The response to catecholamines did not vary significantly during the cycle. The variations in electrical and mechanical activity were characteristic for each stage of the ovarian cycle and could be correlated with the well-known hormonal changes. High circulating estrogen levels in proestrus are associated with infrequent but rapidly propagated spike bursts, whereas low levels in estrus are associated with frequent and sometimes nonpropaged bursts. The rise in plasma estrogen in diestrus coincides with a decrease in the frequency of burst activity, and the elevated progesterone levels are probably causally related to the significant drop in propagation velocity and the increase in duration of bursts observed in diestrus. These findings are consistent with the concept that estrogen withdrawal activates the estrogen-primed, quiescent myometrium, and that progesterone has an effect similar to that of estrogen withdrawal--at least in the rat.

Action Potentials↗

Effects of epinephrine and oxytocin on the release of prostaglandin F from the rat uterus in vitro.

Isolated uteri from rats with regular 4-day cycles were incubated in Krebs-Ringer bicarbonate buffer and the release of PGF into the medium was measured by radioimmunoassay after extraction of the incubation medium with ethyl acetate at pH 3.0-3.5. PGF was produced from endogenous precursors and accumulated in equal amounts in the medium during two successive 60 min periods on each day of cycle, but the magnitude of the production varied significantly during the cycle, being greatest in estrus. Oxytocin in doses up to 500 mU/ml had no effect on PGF accumulation in the incubation period at any stage of the cycle, while epinephrine (10(-3)) greatly stimulated PGF release from the estrous uterus but had no effect on PGF release from the diestrous uterus. Phentolamine, an alpha-blocking agent, had no effect on the epinephrine-induced release of PGF, while propranolol, a beta-blocking agent, not only prevented in increase in PGF production induced by epinephrine but also reduced the basal release of PGF by the estrous uterus. Since oxytocin contracts and epinephrine relaxes the nonpregnant rat uterus both in vivo and in vitro, it is unlikely that the effects of these two compounds on uterine contractility are mediated by the release of PGF2alpha.

Animals↗

The effect of indomethacin on uterine contractility and luteal regression in pregnant rats at term.

Treatment of pregnant rats with 1 mg indomethacin/kg twice daily i.m. beginning on Day 20 delayed the onset of parturition by about 21 hr and prolonged the duration of spontaneous parturition by 4 hr. Plasma progesterone and oestradiol levels were determined in daily samples of peripheral blood, and uterine contractions were recorded before and during parturition by means of small, chronically implanted intrauterine balloons which were connected to pressure transducers via fluid-filled catheters. Indomethacin treatment did not inhibit or suppress spontaneous or oxytocin-induced contractions, which were of the same intensity in indomethacin-treated as in control rats. Parturition was induced with oxytocin in the same proportion of treated and control rats, but its induction was not successful in treated rats until 1 day later than in control rats, but its induction was not successful in treated rats until 1 day later than in controls. The onset of parturition was always related to the plasma progesterone level, which declined at a slower rate in indomethacin-treated than in control rats, reaching baseline values approximately 1 day later in the treated animals. The appearance of 20alpha-hydroxysteroid dehydrogenase in the CL of pregnant rats normally occurs on Day 21 of gestation, but activity was not observed until about 1 (0-3) day later in the indomethacin-treated rats, indicating that luteolysis was retarded. Prostaglandin F-2alpha infusions given on Day 21 reversed the effects of indomethacin treatment on plasma progesterone, luteal 20alpha-hydroxysteroid dehydrogenase activity and the timing and duration of parturition, and reduced the high perinatal mortality associated with indomethacin treatment, suggesting that the effects of indomethacin were related to its inhibitory action on prostaglandin synthetase activity. It is concluded that, in rats, indomethacin exerts its effects on parturition through inhibition of luteal regression which was significantly retarded but not prevented, and that indomethacin does not have a direct effect on myometrial contractility.

Animals↗

Intraovarian pressure changes during ovulation in rabbits.

Contractile elements are found in the ovaries of many species, but it has not been possible to ascertain whether these elements are of importance in the process of ovulation. In this report, we describe changes in intraovarian pressure recorded continuously in vivo in unanesthetized rabbits under normal conditions and under the influence of intravenously injected human chorionic gonadotropin (hCG), as well as following the ovulatory stimulus of normal copulation. The recordings were made by means of small latex balloons (0.02- to 0.04-ml volume) attached to indwelling catheters, inserted into the ovarian stroma, and secured with 6-0 nylon sutures. All 24 rabbits studied showed changes in intraovarian pressure indicative of ovarian contractile activity. The intraovarian pressure changes followed a characteristic pattern which was different from the changes in intratubal pressure, recorded simultaneously from the lumen of the ipsilateral fallopian tube, indicating that the contractions of both organs occurred independently. In normal animals, before an ovulatory stimulus was applied, the ovarian contractility pattern consisted of a series of rapid contractions (average amplitude, 6 mm Hg; average frequency; 8 per minute) occurring with intervals of quiescence lasting from 11 to 36 minutes. The base line tonus was frequently elevated during these series of contractions. Mating or an injection of hCG had no immediate effect on intraovarian pressure but, 6 to 8 hours after the stimulus was applied, ovarian contractile activity increased significantly in all rabbits. This enhanced activity persisted for several hours before returning to initial levels approximately 15 to 18 hours after mating or the hCG injection. This demonstration of increased contractile activity about the time of ovulation suggests that ovarian contractions participate in the process of follicular rupture and the extrusion of ova at ovulation. Prostaglandin F2alpha, norepinephrine, and oxytocin were effective in inducing ovarian contractions.

Animals↗