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Biomedical subjects

A R Fuchs

Publications and source records attributed to A R Fuchs.

At least 55 records · Page 3Linked to original sources
PubMed1989

Oxytocin antagonist (dTVT) and oxytocin receptors in myometrium and decidua.

To investigate whether a putative oxytocin (OT) receptor blocker 1-deamino-[2-D-tyrosine (OEt)-4 threonine-8-ornithine]oxytocin (dTVT) inhibits OT binding to its receptors, we studied binding of [3H]OT to late-pregnant human, guinea pig, and rat myometrial and decidual membranes and competition of dTVT with this binding. Decidua as well as myometrium of all three species bound [3H]OT with high affinity (Kd 1-3 nM) and limited capacity. The concentration of binding sites in decidual membranes was slightly lower than in myometrial membranes in human and guinea pig uterus and twice that of myometrial membranes in day 20 pregnant rat uterus. dTVT competed with [3H]OT with highest affinity in guinea pig myomterium and decidua, the potency ratios ([dTVT]50: [OT]50) being 1.9 and 3.3, respectively. The potency ratios in rat uterine tissues and human decidua were slightly higher (4 to 5) and highest in human myometrium, 23.3. Excess dTVT completely inhibited [3H]OT binding in all six tissues, indicating binding to the same receptor sites. Because of the high-affinity binding of dTVT to oxytocin receptors in human decidua and myometrium, this oxytocin analogue may be a very effective tocolytic agent in the treatment of threatened preterm labor.

Animals↗
PubMed1988

Neurohypophyseal aging: differential changes in oxytocin and vasopressin release, studied in Fischer 344 and Sprague-Dawley rats.

We had previously shown that the hypothalamo-neurohypophyseal vasopressin secreting system is suppressed in aged rats. In the present study, using aged (26 months) male Fischer 344 (F344) rats, we showed that in contrast to vasopressin, oxytocin plasma concentration and hypothalamic content were unaltered in comparison with young (2-3 months) rats; however, based on data from our past and current studies, the neurohypophyseal concentrations of both hormones were found to be decreased in aged rats. We also compared the effect of aging on the oxytocin and vasopressin in secretory functions. Superfusion technique was employed to examine oxytocin and vasopressin release from isolated neural lobes of young (2-3 months) and old (26 months) male F344 and young (2-3 months), middle-aged (12 months) and old (30 months) Sprague-Dawley (SD) rats. Aging affected basal release of oxytocin and vasopressin in a differential manner. Expressed per gland, basal release of oxytocin increased in aged rats of both strains; whereas vasopressin release decreased in SD, and did not change in F344, old rats. The vasopressin responses to electrical stimulation, 56 mM K+ and initial traumatic release were decreased in aged rats; whereas oxytocin responses were either unaltered or decreased much less. All age-related changes were more pronounced in SD than in F344 rats. Thus, while the aging process is associated with a significant impairment in the vasopressin secretory function, the oxytocin secretory function is much less affected by that process. Significant strain differences were observed in the effects of aging on oxytocin and vasopressin release.

Aging↗
PubMed1988

Release of oxytocin and vasopressin by intracerebroventricular vasoactive intestinal polypeptide.

Vasoactive intestinal polypeptide (VIP)ergic nerves innervate both the neurohypophysis and the hypothalamus. To test the hypothesis that VIP is a releasing factor for neurohypophyseal hormones, rats were given intracerebroventricular (icv) infusions of VIP in doses varying from 0.3 pmol/kg.min to 3 nmol/kg.min for 5 min (0.001-10 micrograms/rat). Serial blood samples were drawn from the vena cava for measurement of oxytocin (OT), vasopressin (AVP), and VIP by RIA. After the VIP infusions mean plasma OT and AVP levels rose in a dose-dependent manner; the rise was significant for both hormones at the dose of 300 pmol/kg.min. Peak levels after infusion of 3 nmol/kg.min were greater for OT than AVP [96.1 +/- 14.7 vs. 33.9 +/- 9 microU/ml (mean +/- SE); n = 6]. In addition, the concentration of plasma OT increased more promptly than that of AVP. Plasma OT was significantly raised over control values at 5 min, whereas plasma AVP was not increased until 15 min after the VIP infusion began. The concentration of VIP in peripheral plasma rose somewhat after icv infusions (maximum, 300 pmol/liter 30 min after 10 micrograms/rat), but the rise was only 5% of that observed after systemic infusions of equimolar doses of VIP (maximum, 6000 pmol/liter 5 min after 10 micrograms/rat). Peak plasma OT levels after administration of 3 nmol/kg.min VIP were significantly higher after icv than after systemic infusion of the same dose of VIP reported previously. Intravenous injection of 0.5 ml VIP antiserum with a binding capacity of VIP of 2.3 micrograms/ml before the icv administration of VIP (1 microgram/rat) did not prevent the VIP-induced rise in plasma OT and AVP. These observations suggest a central site of action for VIP in OT and AVP release, probably in the hypothalamus. The results are in harmony with the hypothesis that endogenous VIP is a physiological regulator of OT and AVP release in rats.

Animals↗
PubMed1988

Oxytocin and ovarian function.

(1) Oxytocin is synthesized in the luteal cells of all species so far studied, including the human. Vasopressin is also synthesized, but at a much lower rate. (2) The oxytocin-neurophysin gene is expressed in granulosa cells and granulosa-derived luteal cells but not in theca cells. Ovulation or spontaneous luteinization initiates the gene expression which peaks in the early luteal phase and ceases around mid-cycle. (3) Luteal oxytocin concentrations rise with considerable delay after the peak of specific mRNA and reach maximal levels around mid-cycle. Oxytocin concentrations fall to low levels in the late luteal phase and in pregnancy. (4) Thecal tissue produces substances such as catecholamines and ascorbic acid that stimulate oxytocin secretion in granulosa cells. The adrenergic innervation of thecal tissue provides a source of catecholamines and may therefore serve a modulatory function in ovarian oxytocin secretion. (5) Oxytocin has little or no direct effect on luteal progesterone production. (6) Oxytocin inhibits LH-stimulated prostacyclin production in luteal cells of cows. Oxytocin may induce the release of PGF-2 alpha or lipo-oxygenase products from the ovary but this has not yet been documented. (7) PGF-2 alpha releases oxytocin from the ovary but does not turn off its synthesis. (8) The concept that ovarian oxytocin participates in the luteolytic process is gaining acceptance. In some species (sheep, goat) ovarian oxytocin acts as a hormone causing PGF-2 alpha release from the uterus. In others it acts in a paracrine or autocrine fashion on ovarian prostanoid production (cow, possibly primates).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Changes in the 13,14-dihydro-15-ketoprostaglandin F2alpha and oxytocin level in the 1st trimester following beta-sympathomimetic and intracervical prostaglandin E2 gel administration].

3 ml tylose gel containing 500 micrograms PGE2 was injected into the cervical canal of 23 patients prior to first trimester abortion. 11 patients received 5 mg fenoterol orally before the PGE2-gel application and 12 patients a placebo tablet. The PGFM and oxytocin concentrations in plasma were determined radioimmunologically. The results showed the dominant role of elevated PGFM levels in the clinical prevalence of pain during induced abortion.

Abortion, Induced↗
PubMed1987

Preferential release of oxytocin in response to vasoactive intestinal polypeptide in rats.

Vasoactive intestinal polypeptide (VIP) was infused into the aorta of pentobarbitone-anesthetized rats (n = 12) in stepwise increasing doses of 0.001 to 10 micrograms/rat at rates varying from 0.3 pmol/min/kg to 3000 pmol/min/kg over 3 min. Blood was withdrawn from the vena cava inferior for the measurement of oxytocin (OT) and vasopressin (AVP) by RIA. The loss of blood was compensated for by infusion of isotonic saline (0.9% NaCl with 0.5% human serum albumin). Control rats received this solution only (n = 11). VIP infusions resulted in a dose-dependent increase in plasma OT which was significantly greater than the slight rise observed in the controls. The difference from controls was significant at infusion rates of 3 pmol/min/kg and more. Plasma AVP, on the other hand, did not rise in response to VIP infusions until the infusion rate was increased to 300 and 3000 pmol/min/kg. At these infusion rates, the increments in AVP were much smaller than those of OT, the levels during the highest infusion rates rising to 8.6 +/- 2.8 and 27.2 +/- 4.8 microU/ml, respectively (log normal means). The preferential release of OT in response to exogenous VIP in rats differs from the response in cats where intracarotid administration of VIP resulted in the release of proportionately more AVP than OT. Immunoreactive VIP is found in the hypothalamo-neurohypophyseal system of rats in close proximity of some of the magnocellular neurons as well as within the nerve terminals. This, together with our data, suggests that endogenous VIP may participate in the release mechanism for OT in rats.

Animals↗
PubMed1987

Prostaglandin F2 alpha and oxytocin interactions in ovarian and uterine function.

The oxytocin-neurophysin gene is expressed in several nontraditional sites within the endocrine system. In the ovary its expression in the corpora lutea is initiated by ovulation. Ovarian oxytocin concentrations reach maximal levels around day 11 of luteal cycle and fall to a nadir at estrus. PGF2 alpha has the capacity to release oxytocin from the corpus luteum, and oxytocin in turn releases PGF2 alpha from the uterine endometrium or decidua. This positive feedback loop between the ovary and the uterus ensures the completion of luteolysis in species that depend on the presence of the uterus for the termination of luteal lifespan. Immunization against oxytocin has been shown to disrupt this loop, resulting in much-prolonged luteal cycles. In primates and other species in which luteal life span is independent of the uterus, an oxytocin PGF2 alpha interaction may take place within the ovary itself. At parturition a related interaction takes place which ensures the expulsion of the fetus and placenta in an orderly manner. Oxytocin of both pituitary and ovarian origin reaches the uterus via its blood supply and binds to two types of receptors: one on myometrial cells, the occupation of which initiates contractions, and the other on decidual cells, the occupation of which initiates prostaglandin generation. This prostaglandin diffuses into the adjacent myometrium and augments the oxytocin-induced contractions. In conjunction with a direct softening effect by prostaglandins on the cervix the augmented contractions achieve the force needed to dilate the cervix and expel the fetus. An additional source of oxytocin during labor may be the placenta, another non-traditional site for the occurrence of oxytocin.

Animals↗
PubMed1987

Oxytocin response to conditioned and nonconditioned stimuli in lactating ewes.

We have measured oxytocin release during lactation in the ewe in response to normal tactile sucking stimuli as well as exteroceptive stimuli emanating from the lamb. Four puerperal ewes that had indwelling catheter inserted in the femoral artery while still pregnant were used. Each nursed a single lamb. Each was studied 2 or 3 times between Days 1 and 15 of lactation during a 2.5-h experimental period that was preceded by a 2-h separation from the lamb in the early morning. Samples were taken before and after the lamb was brought within sight and sound of the ewe but without contact, and then 0.5, 1, 5, 10, 15, 30, and 60 min after suckling began. When another suckling episode intervened, the same sampling schedule was immediately restarted. Suckling occurred in an intermittent fashion; 3 to 4 episodes of 2.9 +/- 2.0 (SD)-min duration took place with variable intervals during the 2.5-h experimental period. Exteroceptive stimuli emanating from the lamb caused plasma oxytocin to rise significantly from basal levels of 10.0 +/- 4.5 to 21.8 +/- 5.7 pg/ml (mean +/- SE, n 10, p less than 0.05). This rise was not seen on Day 1 and in only half of the ewes on Day 2, but thereafter the rise occurred in every instance. A further rise in plasma oxytocin was observed in almost all instances (86%) at suckling. Peak levels were usually observed within 1 min. They were quite variable, ranging from 15 pg/ml to 287 pg/ml, and not related to the milk yield, but were significantly greater than spontaneous pulses observed in nonlactating puerperal sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Oxytocin receptors in nonpregnant human uterus.

The concentration and distribution of specific [3H]oxytocin-binding sites in the nonpregnant human uterus were studied. Oxytocin was bound with an apparent Kd of about 1 nM in the crude membrane fractions of the fundus and corpus. A second class of sites with lower affinity and higher capacity for oxytocin also was found. Consistent with its high uterotonic potency in nonpregnant uteri, arginine vasopressin was as effective as oxytocin in inhibiting [3H]oxytocin binding to corpus and fundus membrane preparations. The concentrations of high affinity binding sites in fundus and corpus were similar and were significantly higher than those of membrane fractions from isthmus or Fallopian tubes. The lowest concentration of sites was found in the cervix. Endometrial membrane preparations contained oxytocin-binding sites in about the same concentration as that in the myometrium. The concentrations of oxytocin receptors in all parts of the nonpregnant uterus were somewhat higher in the luteal phase than in the follicular phase. Concentrations were lowest in postmenopausal uteri. The concentrations of oxytocin receptors in nonpregnant uteri were 50-100 times lower than those in uteri near the end of gestation. These differences correspond to the differences in sensitivity to oxytocin between luteal phase and follicular phase and between the nonpregnant and late term uterus. These findings add support to the evidence that the binding sites for oxytocin represent true oxytocin receptors.

Adult↗
PubMed1985

Plasma prostaglandin F2 alpha and plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha levels in women during induction of labor with i.v. infusion of prostaglandin F2 alpha in relation to uterine contractions.

The concentrations of plasma PGF2 alpha and its main metabolite, 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured in serial samples of blood collected in 10 pregnant women at term who were given iv infusions of low doses of PGF2 alpha for induction of labor. Six other women served as controls and were given saline infusions. Uterine contractions began with a mean latency of 62 min in the PGF2 alpha infused women, in controls uterine activity remained unchanged. Plasma PGFM levels had increased significantly 30 min after PGF2 alpha infusion began, rising thereafter in a dose dependent manner. Plasma PGF2 alpha also rose reaching a steady state at 2 hours. No significant changes were observed in the controls. The 6-h infusion resulted in delivery in 5 of the 10 women, in the 5 others the cervical scores increased only by 1.25 points on the average and further treatment was needed to achieve delivery, although prostanoid levels rose to similar levels in all. The data show that when uterine contractions are induced by systemic PGF2 alpha, the levels of PGFM are significantly raised. In spontaneous labor uterine contractions begin long before plasma PGFM rises. Thus, if endogenous PGF2 alpha generation is involved in the initiation of uterine contractions during spontaneous labor, it must be synthetized in the myometrium at quantities too low to raise the levels of circulating PGFM.

Adult↗
PubMed1985

Effect of beta-mimetic tocolysis on cervical ripening and plasma prostaglandin F2 alpha metabolite after endocervical application of prostaglandin E2.

To suppress uterine contractions during cervical ripening induced by prostaglandin E2 (PGE2) gel, beta-mimetic drugs were given orally 30 minutes before PGE2 application to 17 patients with unripe cervix. This prevented the increase in contraction frequency observed during the first four hours after PGE2 application in 17 controls. Nevertheless, cervical ripening proceeded at a similar rate and the clinical outcome was comparable in both groups. Prostaglandin E2 application caused a transient rise in plasma levels of the PGE2 alpha metabolite (13,14-dihydro-15-keto), which was not prevented by pretreatment with beta-mimetics. Patients with premature rupture of the membranes had higher initial plasma PGF2 alpha metabolite levels than those with intact membranes but cervical ripening proceeded with the same rate, and the effect of beta-mimetics was the same in both groups. Thus, cervical ripening induced by PGE2 does not depend on uterine contractions, and increased production of PGF2 alpha is unrelated to the ripening process. There was no difference between the three beta-mimetic agents in the present study.

Adrenergic beta-Agonists↗
PubMed1984

Oxytocin receptors in the human uterus during pregnancy and parturition.

We have determined the concentration and distribution of oxytocin receptors in myometrial and decidual tissues obtained at cesarean section or hysterectomy during pregnancy. Myometrial receptor concentration was low at 13 to 17 weeks but had risen about twelvefold by 37 to 41 weeks. After the onset of labor, either preterm or term, the receptor levels were maximal and significantly higher than before the onset of labor. In cases of failed induction of labor with oxytocin and in postterm pregnancies (43 to 46 weeks), the receptor concentration was significantly lower than in spontaneous labor. Myometrial receptor concentrations in the fundus and the corpus were similar and significantly higher than in the lower part of the uterine segment, and the cervix had the lowest concentration. The parietal decidua had oxytocin receptor concentrations of the same magnitude as the myometrium. These results are consistent with a functional role of endogenous oxytocin in the activation of the human uterus during pregnancy and parturition.

Binding, Competitive↗
PubMed1984

Prostaglandin F2 alpha, oxytocin, and uterine activation in hypertonic saline-induced abortions.

Intra-amniotic injections of hypertonic saline at midgestation induce uterine activity, which evolves into a laborlike pattern in less than 24 hours and is associated with progressive increase in uterine oxytocin response. This uterine activation occurred in the absence of a measurable increase in plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM). Only after 25 to 27 hours was a rise in plasma concentration of PGFM detected, which then increased in a parallel manner with cervical dilatation. By contrast, plasma oxytocin levels increased by almost 100% soon after the injection of hypertonic saline, declining to initial levels by 24 to 28 hours. Oxytocin infusion given after the intra-amniotic injection at rates resulting in about a fivefold increase in plasma oxytocin significantly accelerated cervical dilatation and the rise in plasma PGFM. Oxytocin infused before induction of abortion resulted in only a small and transient rise in plasma PGFM. Hypertonic saline injections thus increase the prostaglandin F2 alpha-stimulating action of oxytocin, which in turn may be responsible for the enhanced contractile response to the hormone. Myometrial activation after hypertonic saline injections is probably caused by an interaction of oxytocin and prostaglandin F2 alpha, and cervical dilatation depends on contractile activity and a critical increase in prostaglandin production.

Abortion, Induced↗
PubMed1984

Cervical ripening and plasma prostaglandin levels. Comparison of endocervical and extra-amniotic PGE2.

Two modes of cervical application of a gel containing PGE2 have been compared in a total of 30 patients with indication for induction of labor and unripe cervix. Fifteen patients had gel injected endocervically; in 10 patients the gel contained 400 micrograms PGE2, in 5 controls the gel was inactive. Fifteen subjects had a 15 ml Foley catheter passed through the cervix and placed extra-amniotically; in 10 of them 3 ml gel with 400 or 800 micrograms PGE2 was injected, while 5 controls received inactive gel. Plasma levels of 13,14-dihydro-15-keto-PGE2 alpha (PGFM) were measured in blood samples drawn before and 1/2, 1, 2, 4, 6, and 8 hours after gel application. Neither the Foley catheter nor the application of inactive gel caused significant changes in the cervical scores or the PGFM levels. PGE2 in the endocervix increased cervical scores without altering plasma PGFM levels. Extra-amniotic PGE2 caused a more rapid increase of the cervical scores and a progressive rise in PGFM levels. The plasma (PGFM) levels were found to be related to the degree and to the rate of cervical dilatation. The correlation with cervical dilatation was highly significant. Labor began spontaneously or after artificial rupture of the membranes in 80% of the extra-amniotic, and 50% of the endocervical PGE2-group, but in none of the controls. These data indicate that increased uterine PGF2 alpha production is not necessary for the early stages of cervical ripening, whereas dilatation beyond 4 cm does not proceed without such increase.

Amnion↗
PubMed1984

[Influence of fenoterol, ritodrine and clenbuterol on maternal oxytocin and PGFM levels].

In this investigation, the Oxytocin (OT) and 13, 14-Dihydro-15 Keto PGF 2-alpha (PGFM) levels were investigated in patients who required ripening of the cervix prior to induction of labour. Under randomized conditions four PGE2-Gel-groups and 1 Placebo group was formed. The patients who received PGE2-Gel were treated either with .4 mg PGE2-Gel intercervically without prior treatment with Betamimetica (n = 6) or 30 minutes prior to the application of .4 mg PGE2-Gel intercervically with 5 mb Fenoterol (n = 6) or 10 mg Ritadrine (n = 6) or 20 micrograms Clenbuterol (n = 6). These drugs were given by mouth. A control group of 6 patients received Gel without PGE2 Placebo. In previous investigations, it was shown that the Oxytocin level rises following the intercervical administration of PGE2-Gel to an unripe cervix whereas the PGFM level remains unchanged. Oral administration of Fenoterol inhibited the PG induced rise of the Oxytocin level and kept the Oxytocin level in the same range as following the administration of a Placebo. The present investigation served to check whether Ritadrine and Clenbuterol had an Oxytocin inhibiting effect as well as Fenoterol. It was found that administration of Betamimetica did not inhibit the ripening effect of PGE2-Gel on the cervix. Although labour did not start in 12 of 18 women treated with Betamimetica during four hours, the cervix ripened in the same manner as in women with labour. The administration of Placebo instead of PGE2-Gel showed no ripening effect (P less than 00001). Following the administration of Fenoterol the maternal heart rate increases significantly compared to Placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Clenbuterol↗
PubMed1984

[Premature membrane rupture: effect of intracervical PGE2 gel administration on plasma oxytocin, PGFM and PGEM levels in mother and child].

Premature rupture (= PR) of the amnion is a serious complication even for the mature child if it occurs earlier than 24 hours before birth. To keep the interval as short as possible, the authors induce labour from week 35/0 in case of PR, provided the Bishop score is greater than 7. If the bishop score is lower, they conduct intracervical priming of the cervix with 0.4 mg PGE2 gel before induction of labour. This has proved clinically superior to intravenous procedures. In the study presented here, the authors attempted to find out whether intracervical administration of PGE2 gel would result in changes in the maternal and foetal plasma concentrations of oxytocin, PGFM, or PGEM when comparing conditions in case of ruptured amnion with those if the amnion remained intact. If the amnion is intact and the cervix immature (less than 2 cm), intracervical administration of 0.4 mg PGE2 gel produces a significant OT increase within 30 minutes. From a cervical width of 2 cm onwards, the OT levels are already primarily enhanced and will hardly change even after PGE2 gel administration. Similar conditions obtain in PR. PGFM plasma levels will rise only slightly within an hour after intracervical PGE2 gel administration, independent of whether there has been a rupture or not, or whether the cervix is dilated less than 2 cm or 2 cm and more.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1984

Endocrinology of human parturition: a review.

The existing data on the hormonal factors involved in human parturition indicate that the steroid hormones, progesterone and the oestrogens, play only a facilitatory role in the initiation of labour. A definite role for fetal adrenal steroids in this process has yet to be established, and they too may serve only a facilitating function. The stimulation of the uterine muscle during labour results from an interaction of oxytocin and prostaglandin (PG) F2 alpha. Recent evidence suggests that oxytocin is most important for the initial phase of labour, whereas increased synthesis of PGF2 alpha is essential for the progression of labour. The role of PGE2 remains unclear, but this PG may play an important role in the ripening of the cervix which in turn is essential for successful parturition. The finding of maximal oxytocin receptor concentrations in the myometrium in labour adds strong support to the notion that oxytocin is the trigger for uterine contractions. The factors which control oxytocin receptor formation are therefore important; this may be one of the processes where the steroids play a crucial role. Oxytocin is also one of the stimuli that increase uterine PG synthesis; the coupling of oxytocin receptor occupancy and PG synthetase activity in uterine tissues may be another crucial factor in the mechanism of labour. The formation of gap junctions between the myometrial cells also seems essential for the synchronization and progression of myometrial activity. We propose, therefore, that the co-ordinating of oxytocin receptor formation, PG synthesis and gap junction formation is a key to the initiation and maintenance of human labour. The fetus may fulfil such a co-ordinating role through its influence on placental oestrogen production, through mechanical distention of the uterus, and through its secretion of neuro-hypophysial hormones and other stimulators of PG synthesis.

Adrenal Cortex Hormones↗