Involvement of prostaglandins in the effect of cupric ions on the human uterus

The effect of cupric ions on the human uterus and the involvement of prostaglandins (PGs) in mediating this effect was studied by recording of isometric contractions of isolated myometrial strips and pieces of uterine arteries, and by intrauterine pressure recordings in women before the onset of menstruation. , CuCl₂ in concentrations of 10⁻⁴ M and higher caused a significant inhibition of myometrial contractile activity, but no effect on the artery preparations was seen. Furthermore, the contractile response of myometrial strips to PGF_2α and PGE₂ (10 ng/ml) decreased in the presence of CuCl₂ in concentrations of 5 and 50 μmol. , instillations of 0.3, 1.0 and 2.0 mM of CuCl₂ in 0.7 ml of saline solution into the uterine cavity caused a dose-dependent stimulation of uterine activity, but after pretreatment with naproxen, 500 mg orally, the effect of these substances was abolished. After naproxen treatment, but during infusion of PGF_2α (5 μg/min), the response to the CuCl₂ solutions was partially restored. It is suggested that cupric ions, at high concentrations, have an inhibiting effect on myometrial activity. The stimulatory effect of low doses of CuCl₂ seen after installation into the uterine cavity is largely exerted via initiation of synthesis and release of endometrial PGs.     

Interaction of vasopressin and prostaglandins in the nonpregnant human uterus

The interaction of vasopressin (VP) and prostaglandins (PG) on the nonpregnant human uterus was studied in vitro and in vivo. In organ baths arginine (A)- and lysine (L)-VP in concentrations of 0.6 to 100 ng/ml stimulated small human myometrial strips and uterine artery preparations to a similar degree. When these VPs were given in the presence of indomethacin or naproxen in concentrations of 1 microgram/ml and 5 micrograms/ml, respectively, the myometrial and arterial responses were not significantly influenced. PGF2 alpha in concentrations of 0.01-100 ng/ml stimulated the myometrial preparations but caused a slight relaxation of the arteries, with PGE2 the myometrial effects were insignificant and the relaxation of the arteries greater. When AVP was given together with either of the PGs to the bath the result was generally a summation of the individual effects of both types of substances.--In vivo during intrauterine pressure recordings in nonpregnant women 1-2 days before onset of menstruation LVP in single intravenous injection of 1.2 micrograms markedly stimulated uterine contractions. The response remained practically unaltered after pretreatment with 500 micrograms of naproxen given orally. The responses to LVP were also closely similar before, during and after intravenous infusion of PGF2 alpha at a rate of 5 micrograms/min.--It is concluded that the effect of VP on myometrium and uterine arteries is not to any great extent mediated by local synthesis of PG and that PGs do not cause potentiation or inhibition of the VP effects on the nonpregnant uterus.     

The effect of acetylsalicylic acid and indomethacin on the catecholamine- and oxytocin-induced contractility and prostaglandin (6-keto-PGF1 alpha, PGF2 alpha)-production of human pregnant myometrial strips

The effects of acetylsalicylic acid (ASA) and indomethacin (IND) on the epinephrine and oxytocin stimulated contractility and prostaglandin (6-keto-PGF1 alpha, PGF2 alpha) production of superfused myometrial strips from the pregnant human uterus at term are reported. Without preincubation in ASA or IND epinephrine dose-dependently (10 ng/ml to 1 microgram/ml) stimulated the contractility and significantly increased the PG-release of the myometrial strips. The epinephrine induced increase in contractility was correlated to a higher increase in PGF2a production and a decreased 6-keto-PGF1 alpha/PGF2 alpha ratio (5.4 to 1.8). Superfusion of oxytocin increased myometrial contractions and PGF2 alpha release according to dose (3-12 microU/ml). However, 6-keto-PGF1 alpha production was not affected by oxytocin. Myometrial strips preincubated with ASA (100 micrograms/ml) or IND (10 micrograms/ml) demonstrated little spontaneous activity and the PG production was below the detection limit of the RIA. The stimulating effect of epinephrine and oxytocin on the contractility and PGF2 alpha release of the myometrial strips was inhibited significantly. During continuous superfusion of the ASA and IND preincubated myometrial strips with Tyrode's solution the inhibitory effect on spontaneous, epinephrine-, and oxytocin-stimulated contractility and PGF2 alpha release gradually declined over a period of 2 hours. This decrease of the inhibitory effect was more significant in ASA preincubated specimens. Our results demonstrate that spontaneous, epinephrine-, and oxytocin-stimulated contractility and PG release of human myometrial strips can be inhibited by ASA and IND and that this inhibitory effect is reversible. Furthermore our results suggest that in pregnant human myometrium the inhibition of PGF2 alpha production by ASA and IND is more pronounced than that of 6-keto-PGF1 alpha (PGI2).     

Interaction of vasopressin and prostaglandins in the nonpregnant human uterus

The interaction of vasopressin (VP) and prostaglandins (PG) on the nonpregnant human uterus was studied and . In organ baths arginine (A)- and lysine (L)-VP in concentrations of 0.6 to 100 ng/ml stimulated small human myometrial strips and uterine artery preparations to a similar degree. When these VPs were given in the presence of indomethacin or naproxen in concentrations of 1 μg/ml and 5 μg/ml, respectively, the myometrial and arterial responses were not significantly influenced. PGF_2α in concentrations of 0.01–100 ng/ml stimulated the myometrial preparations but caused a slight relaxation of the arteries, with PGE₂ the myometrial effects were insignificant and the relaxation of the arteries greater. When AVP was given together with either of the PGs to the bath the result was generally a summation of the individual effects of both types of substances. - In vivo during intrauterine pressure recordings in nonpregnant women 1–2 days before onset of menstruation LVP in single intravenous injection of 1.2 μg markedly stimulated uterine contractions. The response remained practically unaltered after pretreatment with 500 μg of naproxen given orally. The responses to LVP were also closely similar before, during and after intravenous infusion of PGF_2α at a rate of 5 μg/min. - It is concluded that the effect of VP on myometrium and uterine arteries is not to any great extent mediated by local synthesis of PG and that PGs do not cause potentiation or inhibition of the VP effects on the nonpregnant uterus.     

Effects of inhibition of prostaglandin synthesis on uterine oxytocin receptor concentration and myometrial gap junction density in parturient rats

The development of oxytocin (OT) sensitivity in the parturient uterus is associated with increases in myometrial OT receptor concentration, gap junction formation, and prostaglandin (PG) production. To investigate whether PGs mediate these responses, we measured OT responsiveness, OT receptor concentrations, and gap junction formations in uteri of Day 19, 20, 21, 22, 23 pregnant and Day 2 postpartum rats. Inhibition of endogenous PG synthesis was produced by infusion of naproxen sodium delivered by an implanted osmotic pump. Naproxen treatment, but not placebo treatment, markedly attenuated in vitro uterine PGE2, PGF2 alpha, and PGI2 releases, suppressed OT responsiveness, and prolonged gestation. The increase of OT receptor concentration that normally occurred on Day 23 term pregnancy was delayed to Day 24. Co-administration of PGF2 alpha reversed the suppressive effects of naproxen. Naproxen treatment did not significantly affect gap junction formations on Day 23 but appeared to delay both the onset and disappearance of gap junction formations. PGF2 alpha co-administration with naproxen also had no apparent effect on gap junction development. The inhibition of OT receptor formation but not gap junction formation on Day 23 in the presence of naproxen indicates that these two events are controlled independently. Furthermore, the failure of naproxen-treated rats to deliver at term suggests that gap junction formation in the absence of an increase in OT receptors is insufficient to initiate labor. It appears that increases in both OT receptor concentrations and gap junction densities may be required for labor.     

Effects of beta-adrenergic agonist infusions on myometrial activity and plasma prostaglandin levels in the nonpregnant sheep

Recent studies have reported that beta-adrenergic agonists stimulate the production of stimulatory prostaglandins (PGs) by intrauterine tissues in vitro. These drugs are used clinically to inhibit uterine contractions; consequently an increase in stimulatory PGs in vivo might have potentially adverse effects. We have, therefore, investigated whether beta-adrenergic agonists increase plasma PG concentrations in vivo. Samples of peripheral (aorta) and uterine venous enriched (vena cava) blood from nonpregnant sheep were collected at 15-min intervals for 1 h before, 3 h during, and 1 h postinfusion of either (a) the beta-adrenergic agonist isoproterenol (Isop) at a dose of 0.16 microgram.kg-1.min-1; (b) Isop at a dose of 0.08 microgram.kg-1.min-1; or (c) saline, 1 mL/h via a jugular vein catheter. The sheep were also equipped with intrauterine recording balloons to record intrauterine pressure and myometrial electromyographic (EMG) electrodes to measure EMG activity. Infusion of Isop at 0.16 microgram.kg-1.min-1 produced a significant initial inhibition of uterine activity, although contractions returned (within 60 min) despite continued administration of Isop. Plasma PGE2 (but not PGF2 alpha or 13,14-dihydro-15-keto-PGF2 alpha (PGFM] concentrations were significantly elevated during the Isop infusion. Administration of Isop at 0.08 microgram.kg-1.min-1 produced no effects on uterine contractile activity but was associated with a significant elevation in plasma PGE2 (but not PGF2 alpha or PGFM) concentrations. No changes in plasma PGE2, PGF2 alpha, or PGFM occurred during saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxytocin enhances the basal release of uterine prostaglandin F2 alpha, but not that of PGE1, or of PGE2, and changes the metabolism of exogenous arachidonate, favouring the formation of prostaglandin F2 alpha and 5-HETE. Relationships with its uterotonic action and modulation by estradiol

We attempted to explore possible mechanism(s) subserving the influence of oxytocin on uterine motility by studying the action of the hormone on: 1) the contractile activity of isolated rat uteri in the presence or absence of indomethacin; 2) the synthesis and release of prostaglandins (PGs) into the solution incubating the uterine tissue as well as the metabolism of labelled arachidonic acid; 3) the uptake of 45Ca2+ by uterine strips. The experiments were bone with uterine preparations isolated from spayed rats treated or not with 17-beta-estradiol. The values of isometric developed tension (IDT) and of frequency of contractions (FC) induced by oxytocin in uterine strips isolated from spayed and spayed-estrogenized rats, were not modified by indomethacin at 10(-6) M. On the other hand, uterine strips from untreated spayed rats, release into the incubating medium approximately equal amounts of PGE1, PGE2 and PGF2 alpha. The in vitro presence of oxytocin (50 mU/ml) increased significantly (p 0.05) the output of PGF 2 alpha without changing the release of PGE1 or PGE2. Uteri from spayed rats injected prior to sacrifice with 17-beta-estradiol released significantly less PGE1 and PGE2 (p less than 0.005) than preparations from non-injected animals, whereas the output of PGF2 alpha in the suspending solution remained unchanged. Following estrogenization the addition of oxytocin to preparations obtained from spayed-estrogenized rats also increased the output of uterine PGF2 alpha (p less than 0.001) without changing that of PGs E1 or E2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of enzymes of cyclooxygenase pathway and secretion of prostaglandin E2 and F2alpha by porcine myometrium during luteolysis and early pregnancy

Past studies of uterine prostaglandin (PGs) and pig reproduction have focused on endometrial rather than myometrial PGs. This study documents the synthesis and secretion of myometrial prostaglandins (PGs) in pigs and the involvement of oxytocin (OT) in these processes. Cyclooxygenase-2 (COX-2) expression was similar in myometrial explants from cyclic and pregnant pigs (days 14-16) and OT (10(-7) M) in vitro significantly increased COX-2 protein regardless of reproductive state. Basal expression of prostaglandin E2 synthase (PGES) was higher during pregnancy than during luteolysis. Conversely, prostaglandin F synthase (PGFS) was highest during luteolysis and lower in myometrium from gravid animals. OT had no influence on the expression of PGES and PGFS. In another tissue culture experiment, myometrial slices produced more PGE2 than PGF2alpha regardless of reproductive state of the female. OT stimulated PGE2 production in myometrium harvested during luteolysis and increased PGF2alpha production in all tissues examined. Progesterone (P4; 10(-5) M) blocked stimulatory effect of OT on myometrial PG release. Myometrial OTr mRNA was higher (P=0.03) during luteolysis than during pregnancy. In conclusion: (1) oxytocin increases myometrial COX-2 expression, but does not influence the expression of terminal enzymes of PGs synthesis (PGES and PGFS); (2) porcine myometrium preferentially produces PGs during early pregnancy and secretes more PGE2 than PGF2alpha; (3) myometrial OT and OTr support secretion of PGs from myometrium during luteolysis.     

The influence of polychlorinated biphenyls (PCBs) and phytoestrogens in vitro on functioning of reproductive tract in cow

Ovarian, endometrial and myometrial cells and strips of longitudinal myometrium from cows on defined days of estrous cycle were treated for 24-72 h with different doses (1-100 ng/ml) of PCBs mixture (Aroclor 1248) or with one of PCB congeners (126, 77, 153). The administered doses of PCBs neither affected the viability of cells nor influenced the ovarian steroidogenesis as measured by progesterone (P(4)), estradiol (E(2)) and testosterone secretion from luteal, granulosa and theca cells, respectively. In contrast, PCBs clearly inhibited a FSH and LH-stimulated effect on steroids secretion from granulosa and luteal cells. Moreover, PCBs significantly stimulated oxytocin (OT) secretion from the studied ovarian cells, and at least part of this effect is elicited through activation of glucocorticoid receptors. Further, PCBs were found to increase basal intracellular concentrations of Ca(2+) and both spontaneous and OT-stimulated contractions of myometrial strips. Concomitantly, PCBs increased endometrial secretion of PGF(2alpha), hence the ratio of PGF(2alpha):PGE(2) was also increased. Phytoestrogens (genistein, daidzein, coumestrol), with a different intensity, reduced the effect of PCBs on PGF(2alpha) secretion and myometrial contractions. Genistein inhibited PCBs' effect on OT secretion from granulosa cells, while PCB's effect on OT release from luteal cells was reduced mainly by genistein and daidzein. We conclude that PCBs can impair both ovarian functioning and uterine contractility, while phytoestrogens are able to reduce this effect.     

In vitro release of PGF(2alpha) from the caprine uterus and the effect of ovarian steroids

The purpose of the study was to determine the in vitro release of prostaglandin F(2)alpha (PGF(2alpha)) from the uterine tissues of ovariectomized goats after steroid treatment. Strips of endometrial tissues (separated by trypsin treatment) and intact uterine tissues (with endometrium and myometrium) were maintained in organ culture and exposed to estradiol-17beta(E) at 50 ng/ml and to progesterone (P) at 250 pg/ml alone or in combination. The endometrial tissues, in general, continued to release PGF(2alpha) without steroids treatment throughout the 96-h incubation period; their output was consistently higher (based on ng/gm of wet tissue) than the corresponding intact uterine tissues. However, exposure to E reversed this trend and produced a three-fold increase from the intact uterine strips at 24 h. A combined E-plus-P treatment blocked the stimulatory response, whereas P treatment alone evoked a delayed stimulatory response at 48 h. Endometrial tissue reaction was similar to that of P treatment, but it exhibited a more moderated response to E, which could not be blocked by a combined E-plus-P treatment. The results suggest that both endometrial and myometrial tissues release PGF(2alpha) and that this release is regulated by ovarian steroid hormones.     

Discriminating analysis of "in vitro" prostaglandin release by myometrial and luminal sides of the ewe endometrium

An original perifusion device which allows a discrimination between the 30 mn releases of prostaglandins F2 alpha and E2 by the luminal and the myometrial faces of sheep endometrium is described. Tissue was sampled on day 4, 14, 16 or 17 of the cycle and on day 14 or 17 of pregnancy. Total prostaglandin (PG) release measured with this device was in good agreement with PG's concentrations in media of in vitro endometrium incubations already described. Discrimination analysis of the PGs release by each side of the endometrial tissue during the 30 mn perifusion time revealed that PGF2 alpha concentrations of the perifusion medium issued from the lumen compartment were higher than those of the myometrial compartment in all physiological status where corpus luteum is active (including early pregnancy). Therefore in the ewe, it seems that luteal structure maintenance during early pregnancy is not due, as in the gilt, to a shift in PGF2 alpha secretion towards the uterine lumen.     

Prostacyclin induces a surprising long-lasting motility in quiescent uterine strips (indomethacin-treated) isolated from ovariectomized rats

Dose-response curves for several prostaglandins (PGI2; PGD2; PGF2 and PGE2); BaCl2 or prostaglandin metabolites (15-keto-PGF2 alpha; 13,14-diOH-15-keto-PGF2 alpha; 6-keto-PGF1 alpha and 6-keto PGE1 in quiescent (indomethacin-treated) uterine strips from ovariectomized rats, were constructed. All PGs tested as well as BaCl2, triggered at different concentrations, evident phasic contractions. Within the range of concentrations tested the portion of the curves for the metabolites of PGF2 alpha was shifted to the right of that for PGF2 alpha itself; the curve for 6-keto-PGF1 alpha was displaced to the right of the curve for PGI2 and that for 6-keto-PGE1 to the left. It was also demonstrated that the uterine motility elicited by 10(-5) M PGF2 alpha and its metabolites was long lasting (more than 3 hours) and so it was the activity evoked by PGI2;6-keto-PGF1 alpha and BaCl2, but not the contractions following 6-keto-PGE1, which disappeared much earlier. The contractile tension after PGF2 alpha; 15-keto-PGF2 alpha; 13,14-diOH-15-keto-PGF2 alpha and PGI2, increased as time progressed whilst that evoked by 6-keto-PGF1 alpha or BaCl2 fluctuated during the same period around more constant levels. The surprising sustained and gradually increasing contractile activity after a single dose of an unstable prostaglandin such as PGI2, on the isolated rat uterus rendered quiescent by indomethacin, is discussed in terms of an effect associated to its transformation into more stable metabolites (6-keto-PGF1 alpha, or another not tested) or as a consequence of a factor which might protects prostacyclin from inactivation.     

Oxytocin receptors and contractile response of the myometrium after long term infusion of prostaglandin F2 alpha, indomethacin, oxytocin and an oxytocin antagonist in rats

Binding of [3H]oxytocin to isolated myometrial plasma membranes was not affected by the presence of prostaglandin (PG)F2 alpha or E2 in the incubation medium. Long-term treatment with PGF2 alpha or indomethacin had no effect on oxytocin receptor concentrations and dissociation constants of myometrial plasma membranes nor on maximal contractility or KM values of isolated uterine strips exposed to oxytocin. Infusion of oxytocin for 5 days in non-pregnant rats resulted in a decrease in oxytocin receptor concentrations in myometrial plasma membranes whereas the binding affinity to oxytocin was unaffected. Isolated uterine strips from similarly treated rats showed a reduced maximal contractile response to oxytocin and an elevated KM value, possibly indicating an influence of oxytocin on the coupling between receptor occupancy and contractility. Treatment for 5 days with desamino1-[D-Tyr(O-ethyl)2-Thr4-Orn8] oxytocin (an oxytocin antagonist) increased the concentration of myometrial oxytocin receptors. In addition KD values of these receptors were elevated. The present results indicate that prolonged exposure to oxytocin leads to a down-regulation of the myometrial receptor concentration, which is not caused by ligand-receptor interaction in itself. The concerted effect of oxytocin and prostaglandins on myometrial contraction does not appear to involve modulation of the oxytocin receptor by prostaglandins.     

Different responses to prostaglandin F2 alpha and E2 in human extra- and intramyometrial arteries

Tubal segments of the ascending uterine arteries and of intramyometrial arteries were obtained from 18 women who underwent hysterectomy at various phases of the menstrual cycle. Ring preparations of the vessels were mounted in organ baths and isometric tension was recorded. In extramyometrial arteries (outer diameter 2-3 mm) prostaglandin (PG) F2 alpha most potently, but also PGE2 caused concentration-related contractions. In contrast, the contractant effects of both PGs on intramyometrial arteries (outer diameter 0.5-0.6 mm) were negligible. Both extra- and intramyometrial vessels were relaxed to a moderate degree (10-25%) by low concentrations of PGF2 alpha and PGE2. No significant differences between the responses to vasopressin and noradrenaline were found between the vessel preparations. Thus human uterine arteries seem to change their responses to PGF2 alpha and PGE2 as they enter the myometrium and decrease in diameter, and the results raise doubt about the view that direct vasoconstrictor effects of these PGs contribute to the regulation of myometrial blood flow. Such effects of vasopressin and noradrenaline cannot be excluded.     

Tissue levels of prostaglandins and what do they mean? Studies on the guinea-pig uterus

The ratios of the concentrations of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha in guinea-pig uterine horns, which were removed and placed in ethanol in 1.5 to 2 min, were 0.3:1.0:0.6 on day 7 and 13.8:1.0:0.8 on day 15 of the oestrous cycle. Adding indomethacin (10 micrograms/ml) to the ethanol had no significant effect on the tissue levels observed. These ratios were similar to the ratios of the outputs of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha from the guinea-pig uterus (0.6:1.0:0.9 on day 7 and 7.6:1.0:1.5 on day 15), but were different (particularly on day 7, but only for 6-keto-PGF1 alpha on day 15) to the ratios of the amounts of the three PGs synthesized by homogenates of the guinea-pig uterus (7.2:1.0:2.4 on day 7 and 11.7:1.0:3.3 on day 15). Consequently, the measurement of tissue levels of PGs in the guinea-pig uterus reflects PG synthesis by intact tissue and changes in this synthesis, rather than PG synthesis by homogenates (broken cell preparations). Therefore, it appears meaningful to measure levels of PGs in the guinea-pig uterus since they reflect uterine PG output. Separation of the endometrium from the myometrium, which involved handling and mild trauma, stimulated uterine PG levels, but the ratio of the levels of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha in the endometrium was still similar to that found in the non-separated uterus.     

Stimulation of ovine myometrial activity by 6-keto prostaglandin E1

6-keto prostaglandin E1 (6KE) is a metabolite of PGI2, which we have shown previously inhibits spontaneous myometrial activity. In the present study we examined the effects of 6KE on uterine electrical and mechanical activity in non-pregnant ovariectomized sheep. 6KE stimulated uterine activity in a dose-dependent fashion. The effect was enhanced by pre-treatment with estradiol (E2). It was not influenced by pre-treatment with meclofenamic acid and was not associated with significant changes in the concentrations of 13,14 dihydro 15-keto PGF2 alpha in vena cava plasma. After E2 treatment, 6KE had 0.2-0.3 of the stimulatory activity of PGF2 alpha. In the absence of E2, the uterine response to both 6KE and PGF2 alpha was decreased. In animals in which spontaneous myometrial activity was inhibited by PGI2, the uterus remained responsive to 6KE. We conclude that in the ovariectomized non-pregnant sheep 6KE stimulates uterine activity, and that the effect is independent of endogenous PG production.     

On the role of 'in vivo' injected progesterone and of the 'in vitro' presence of oxytocin, modulating Ca2+ uptake by the rat uteri from spayed animals and as controllers of the production of arachidonic acid metabolism.

We attempted to explore possible mechanism(s) subserving the influence of oxytocin (O) and of progesterone (P) in the isolated rat uterus studying the action of these hormones on: the synthesis and release of prostaglandins (PGs), the metabolism of labelled arachidonic acid and the uptake of Ca2+ by the tissue from ovariectomized animals. The experiments were done with uterine preparations isolated from spayed rats treated or not with P prior to sacrifice and afterward incubated or not with O 'in vitro'. While uterine strips from untreated spayed rat uterus exhibited a basal release into the incubating medium of approximately the same amounts of PGF2 alpha, and PGE2, the 'in vitro' addition of O (50 mU/ml) increased significantly (p < 0.05) the output of PGF2 alpha without changing the release of PGE2. In tissue from rats injected with P prior to sacrifice the output of PGF2 alpha rose significantly (p < 0.01) as it did after the addition of O to preparations obtained from spayed rats treated with P in comparison to findings in uteri from spayed rats but not in comparison to uteri from spayed rats treated with P alone. Moreover, the 'in vitro' addition of O (50 mU/ml) only increased the formation of PGF2 alpha (p < 0.05) and of 5-HETE (p < 0.05); nevertheless the administration of P to spayed rats diminished significantly (p < 0.05) the formation of 6-keto-PGF1 alpha from uteri, but increased that of PGF2 alpha (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Concentrations of endogenous prostaglandin F2alpha in boar semen and effect of a 72-h incubation period on exogenous prostaglandin F2alpha concentration in extended boar semen

PGF2alpha in semen has been shown to induce uterine contractions, thereby, facilitating sperm transport during fertilization. Previously, we demonstrated that extended boar semen used in artificial insemination does not increase myometrial contractility, but PGF2alpha supplementation did. In this study, we determined the concentrations of endogenous PGF2alpha in pre-sperm and sperm-rich fractions of the boar ejaculate and examined whether changes in the concentration of exogenous PGF2alpha occurred when added to extended boar semen after 72-h incubation at a 17 degrees C storage temperature. Concentrations of endogenous PGF2alpha (n = 10 boars) in pre-sperm and sperm-rich fractions were 69.6 +/- 7.6 and 58.9 +/- 4.4 pg/ml, respectively. No differences were observed in the concentrations of exogenous PGF2alpha in the extended boar semen at 0 h (59.3 +/- 3.3 microg/ml) and after a 72-h incubation period (52.0 +/- 2.1 microg/ml). These results suggest that the concentration of endogenous PGF2alpha in boar semen used for artificial insemination is < 100 pg/ml. The concentration of exogenous PGF2alpha in the extended boar semen did not differ after 72 h, which indicates that it is not metabolized during this period of time.     

The influence of xanthines on the contractile responses of PGF2 alpha and PGD2 in human parenchymal strips

Prostaglandins (PGs) F2 alpha and D2 are bronchoconstrictor agents which are released under allergic conditions such as asthma. The efficacy and potency of PGF2 alpha and PGD2 differ in some tissues. We compared the effects of these two PGs in sensitized human parenchymal strips. In six experiments, PGF2 alpha 0.1 and 0.3 microM produced greater contractions than PGD2 at the same concentrations. There were no significant differences between the contractions from the two PGs at concentrations of 0.01, 0.03, 1.0-10 microM and the two PGs appeared to be equipotent. We studied the effects of the anti-asthmatic drug theophylline, and its analogue enprofylline, on the contraction caused by these PGs. Theophylline 100 microM caused no change to the cumulative concentration response curves. However, enprofylline 100 microM reduced the PGF2 alpha-induced contractions.     

Biosynthesis and catabolism of prostaglandin F2alpha (PGF2alpha) are controlled by progesterone in the rat uterus during pregnancy

Myometrial quiescence is a key factor in all species to accomplish a successful gestation. PGs play a crucial role in mediating parturition events, and their synthesis and metabolism are regulated by cyclooxygenases (COXs) and NAD(+)-dependent 15-hydroxy-PG dehydrogenase (PGDH), respectively. Progesterone (P(4)) is the hormone responsible for maintaining uterine smooth muscle quiescence during pregnancy. In this work, we have studied the effect of P(4) on the activity of COXs and PGDH, the uterine enzymes involved in the biosynthesis and metabolism of prostanoids in the rat. We found that during pregnancy PGF(2alpha) production and also protein levels of COX-1 and COX-2 were decreased. The exogenous administration of P(4) significantly inhibited the uterine production of PGF(2alpha) and also the protein level of COX-2. PGF(2alpha), metabolism was assessed by PGDH activity, which resulted high during pregnancy and increased as a result of P(4) administration. These results indicate that PGs levels were negatively modulated by P(4), which could be exerting its effect by increasing PGs metabolism through stimulation on PGDH activity and an inhibition on COX and that is a major mechanism for maintain uterine quiescence in pregnancy.