Effects of the fetal-placental unit on uterine prostaglandin levels at term in the pregnant rat

Uterine prostaglandins (PGs) increase markedly at term in the pregnant rat. To assess the contribution of the fetal-placental unit (FPU) on uterine tissue and uterine venous blood PG concentrations, each uterine horn of 14 unilaterally pregnant rats at day 21 of pregnancy were compared. In addition, 7 bilaterally pregnant rats were studied. Uterine tissue and uterine venous plasma PGF, PGE, 6-Keto-PGF1 (6KF) and thromboxane B2 (TxB2) and systemic plasma progesterone, estradiol and estrone were determined by radioimmunoassay. Uterine concentrations of PGs (ng/mg DNA) were always greater on the pregnant side of unilaterally pregnant rats (p less than .05) although the PGF levels were elevated to a lesser extent than were PGE, TxB2 or 6KF. However, no differences were detected between uterine tissue from the pregnant side of unilaterally pregnant compared to bilaterally pregnant rats. In addition, no differences were found in uterine venous plasma PGs adjacent or opposite the pregnant uterine horn and in systemic plasma progesterone, estradiol and estrone levels in unilaterally vs bilaterally pregnant rats. These data suggest that the presence of the FPU is associated with an increased capacity of uterine tissue to produce PGE, TxB2 and 6KF, and to a lesser degree PGF, and thus may contribute to the increase in uterine PGs periparturition.     

Temporal response of uterine prostaglandins to estradiol treatment in the ovariectomized-prenant rat

Previous studies in our laboratory have shown that 24 hours of estradiol treatment significantly enhanced uterine prostaglandin (PG)F, PGE and thromboxane B₂ (TxB₂) leels but had no effect on 6-Keto-PGF_1α (6KF) concentrations in ovariectomized-pregnant rats. One explanatior for the lack of an augmentation in 6KF was a temporal differences in response (i.e. 6KF increased and decreased within the 24 hour period). To test this possibility rats were ovariectomized on day 19 of pregnancy and sacrificed 0, 4, 8, 12, 16, 20 and 24 hours after estradiol treatment. Uterine tissue and venous plasma were analyzed for PGs by radioimmunoassay. No significant (p > .05) alterations were detected for any of the uterine PGs at 0, 4, 8 and 12 hours. However, at 16 hours PGF, TxB₂ and PGE all showed significant (p > .05) increases (2.4, 3.4 and 2.1 fold, respectively) compared to 12 hours. In contrast, no significant augmentation in 6KF levels (p > .05, 1.3 fold) was detected at 16 compared to 12 hours although it was enhanced relative to 0 and 4 hours. In addition, PGF, TxB₂ and PGE, but not 6KF, showed further increases 24 hours after estradiol administration. No alterations were found (p > .05) for any of the PGs in uterine venous plasma at the time points studied. In summary, uterine PGF, PGE and TxB₂ net production appears to be more enhanced by estradiol treatment than 6KF at the time points studied. In addition, there is a slight, but significant, difference in the temporal response characteristics of 6KF compared to the other PGs. The data suggest that the dramatic increase in uterine PGF, PGE and TxB₂ levels at parturition in the rat are probably significantly related to enhanced levels of estradiol. However, the majority of the increase in uterine 6KF levels at labor is more likely caused by factors other than augmented plasma estradiol.     

Contributions of the fetoplacental unit to augmented uterine prostaglandin levels periparturition in the rat

The purpose of the present study was to determine if the acute alterations in uterine prostanoid levels at the end of pregnancy are influenced locally by the fetoplacental unit (FPU). Unilaterally pregnant rats were killed on Days 20 and 21 of pregnancy (delivery = Day 21.5) and uterine tissue was removed and analyzed for prostaglandin (PG) E, PGF, thromboxane B2 (TxB2), and 6-keto-PGF1 alpha (6KF) by radioimmunoassay. A significant (P less than 0.05) main effect of Day (20 vs. 21) and Uterine Horn (nonpregnant vs. pregnant), but no interaction for PGE, PGF, and TxB2 was detected. In contrast, a significant interaction (P less than 0.05) of Day with Uterine Horn was found for uterine 6KF levels. Examination of the simple main effects indicated an enhanced level (P less than 0.05) of 6KF in uterine tissue adjacent compared to opposite the FPU at Days 20 and 21. However, uterine 6KF levels in the nonpregnant, but not pregnant, uterine horn were greater at Day 21 compared to Day 20 of pregnancy. The lack of a significant interaction of the main effects for PGE, PGF, and TxB2 suggests that the increased levels of these PGs between Days 20 and 21 were proportional in the nonpregnant and pregnant uterine horn. Therefore, the factor(s) responsible for the augmentation in these uterine PG levels between Days 20 and 21 is(are) most likely arriving via systemic circulation. In addition, the proportionate increases in uterine PGs imply that the FPU is not conferring upon adjacent uterine tissue any unique ability to respond to systemic factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temporal response of uterine prostaglandins to estradiol treatment in the ovariectomized-pregnant rat

Previous studies in our laboratory have shown that 24 hours of estradiol treatment significantly enhanced uterine prostaglandin (PG)F, PGE and thromboxane B2 (TxB2) levels but had no effect on 6-Keto-PGF1 alpha (6KF) concentrations in ovariectomized-pregnant rats. One explanation for the lack of an augmentation in 6KF was a temporal difference in response (i.e. 6KF increased and decreased within the 24 hour period). To test this possibility rats were ovariectomized on day 19 of pregnancy and sacrificed 0, 4, 8, 12, 16, 20 and 24 hours after estradiol treatment. Uterine tissue and venous plasma were analyzed for PGs by radioimmunoassay. No significant (p greater than .05) alterations were detected for any of the uterine PGs at 0, 4, 8 and 12 hours. However, at 16 hours PGF, TxB2 and PGE all showed significant (p less than .05) increases (2.4, 3.4 and 2.1 fold, respectively) compared to 12 hours. In contrast, no significant augmentation in 6KF levels (p greater than .05, 1.3 fold) was detected at 16 compared to 12 hours although it was enhanced relative to 0 and 4 hours. In addition, PGF, TxB2 and PGE, but not 6KF, showed further increases 24 hours after estradiol administration. No alterations were found (p greater than .05) for any of the PGs in uterine venous plasma at the time points studied. In summary, uterine PGF, PGE and TxB2 net production appears to be more enhanced by estradiol treatment than 6KF at the time points studied. In addition, there is a slight, but significant, difference in the temporal response characteristics of 6KF compared to the other PGs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in uterine and placental prostaglandin F and E with gestational age in the rat

Experiments were designed to determine the chronological alterations in placental and uterine prostaglandin F and E (PGF and PGE) during pregnancy in the rat. Pregnant rats (sperm in the vagina = day 0) were sacrified at days 15, 18,19, 20, 21 and delivery (day 21 ) and placental and uterine tissues assayed (RIA) for PGF and PGE immediately (“ ”) or after 1 hour incubation (“ ”). Uterine content of PGF and PGE (ng PG/mg DNA) was increased significantly by day 19 and further increases were seen through delivery. Incubation of uterine tissue resulted in enhanced net production of PGF and PGE (p <.05) per mg DNA (as judged by tissue content and release into the incubation medium) by day 18 of pregnancy vs. day 15. Net production peaked around the time of delivery thus paralleling the alterations in tissue content .By contrast, no differences with gestational age were found in placental content of PGF and PGE , the concentrations throughout late gestation remaining in the range of uterine PGs at day 15. However, production of PGs per mg placental DNA increased markedly during incubation with significant enhancement detected by day 19 vs. 15, achieving levels even greater than the uterus .The and findings for the uterus are consistent with the hypothesis that increases in uterine PGs levels at the end of pregnancy may play an important role in parturition. The experiences with placental tissue suggest that the potential for PG production per placental cell may also increase in late gestation and thereby contribute to the augmented intrauterine availability of PGs at that time.     

Influences of estradiol and of catechol and non-catechol estrogens on the output of prostaglandins in uteri from spayed rats

The effects of 17-beta estradiol and of some catechol and non-catechol-estrogens on the synthesis and output of prostaglandins (PGs) E and F by uteri from ovariectomized rats, were explored. Uteri from castrated animals released twice as much PGE than PGF. When uterine tissue was obtained from spayed rats injected prior to sacrifice with a low dose of 17-beta estradiol (0.5 + 1.0 microgram, on two consecutive days), the output of PGE diminished significantly. With a higher dose of the hormone (0.5 + 50.0 micrograms) the depressive influence on the synthesis and release of PGE was even more marked, whereas the output of PGF rose significantly. Low or high doses of estrone or of estriol failed to affect the release of either one of the PGs determined. On the other hand, 2-0H-estradiol at a low dose had no action but at a higher one inhibited the release of PGE without influencing PGF. Neither low nor high doses of 2-0H estriol or of 2-0H estrone affected the synthesis and release of uterine PGs. It was also observed that all the compounds tested evoked a significant uterotrophic action. It appears plausible that some catechol metabolites of 17-beta estradiol, but not other catechol-estrogens, could be involved in the mechanism of action of 17-beta estradiol modulating the production of PGs by the rat uterus.     

Prostaglandins F in uterine and ovarian compartments and in plasma from the uterine vein, ovarian artery and vein, and abdominal aorta of pseudopregnant rats with and without deciduomata

Prostaglandins F were measured in uterine and ovarian compartments and in uterine venous, ovarian arterial and venous and abdominal aorta plasma and the uptake of ³H-PGF_2α by ovarian compartments of 240 pseudopregnant rats with or without bilateral deciduomata in five experiments. Concentrations of PGF in deciduomal tissue, uterine venous plasma, ovarian arterial and venous plasma, corpora lutea, and remainder of the ovary and ³H-PGF_2α in the ovary were consistently as high or higher in pseudopregnant rats with deciduomata as in the endometrium, ovarian compartments, or samples of plasma from the same blood vessels of pseudopregnant rats without deciduomata jtLevels of PGF were consistently 3 to 7 fold higher in uterine venous than in plasma from the abdominal aorta. It is concluded that extended luteal maintenance by deciduomal tissue is by some mechanism other than an inhibition of PGF synthesis by the uterus, transfer of PGF locally to the ovary, or uptake of PGF by the ovarian compartments.     

A study of prostaglandin F2α as the luteolysin in swine: V comparison of prostaglandin F, progestins, estrone and estradiol in uterine flushings from pregnant and nonpregnant gilts

Uterine flushings were collected from 38 gilts representing Days 6,8,10,12,14,15,16 and 18 of the estrous cycle and pregnancy. The same group of gilts were represented within each of the respective days of the estrous cycle and pregnancy, i.e., three to six gilts per day per status. Uterine flushings (about 40ml) were assayed for prostaglandin F (PGF), estrone (E₁), estradiol (E₂), progestins (P) and protein. Nonpregnant gilts had higher (P<.01) concentrations of P in uterine flushings than pregnant gilts, but pregnant gilts had higher (P<.01) E₁ and E₂ concentrations. Significant day by status interactions were detected for E₁ (P<.05), but not for E₂ concentrations in uterine flushings. Total recoverable PGF and PGF concentrations in uterine flushings were greater (P<.01) in pregnant than nonpregnant gilts and significant (P<.01) day by status interactions were detected. In nonpregnant gilts, PGF increased between Days 12 and 16, i.e., during the period of corpora lutea (CL) regression. In pregnant gilts, PGF in uterine flushings increased markedly between Days 10 and 18. Total recoverable PGF on Day 18 of the estrous cycle was only 464.5 ± 37.6 ng as compared to 22,688.1 ± 1772.4 ng on Day 18 of pregnancy. Total recoverable protein was also higher (P<.01) in pregnant gilts. These data indicate that PGF synthesis and secretion by the uterine endometrium and/or conceptuses is not inhibited during pregnancy and suggest that PGF is sequestered within the uterine lumen of pregnant gilts, as is the total protein component of endometrial secretions referred to as histotroph.     

Prostaglandin translocation from the lumen of the rabbit uterus in vitro in relation to day of pregnancy or pseudopregnancy

Transport of 3H-labeled prostaglandins (PGs) E2 and F2 alpha from the uterine lumen across the uterine wall has been studied in rabbit uteri in vitro in incubations lasting up to 180 min, in relation to sexual state of the rabbit, incubation temperature, intraluminal PG concentration, addition of metabolic inhibitors and time of incubation. PG accumulation by the tissue increased rapidly up to 30 min and then remained relatively constant. By 30 min, radioactivity was found in the external incubation medium, and this increased linearly with time. The translocation of PGF2 alpha was significantly greater in pseudopregnant than in pregnant animals on Day 6, whereas that of PGE2 was significantly higher in pregnant than in pseudopregnant animals on Day 6.8. In pregnant animals, both PGF2 alpha and PGE2 were translocated to the exterior more rapidly on Day 6.8 than on Days 5 or 6. Transport of PGs was reduced by low temperature, unaffected by metabolic inhibitors and only that of PGE2 increased with increased (5 microM) intraluminal concentrations. During incubation, the tissue remained viable as judged by T/M ratios (dpm tissue/dpm medium) for 204 thallium. Transport of [14C] sucrose was much slower than that of [14C] urea, which was greater than the fastest rates exhibited by the PGs. In general, amounts of radioactivity found in antimesometrial, mesometrial and lateral portions of the uterine wall, or in implantation and interimplantation areas did not differ, but more was found in the endometrium than the myometrium. PGF2 alpha was translocated unmetabolized to the external medium, while only two-thirds of the PGE2 was translocated unchanged, and one-third converted to PGF2 alpha. It is concluded that the rabbit uterus shows some selectivity in handling PGs in relation to stage of pregnancy.     

Prostaglandin in teh uterus: Modulation by steroid hormones

Phospholipase A₂ (PLA₂), one of the enzymes considered to be rate-limiting in generating free arachidonic acid for prostaglandin (PG) synthesis, endogenous concentrations and $\text{in vitro}$ production of PGs in the rat uterus were studied under various experimental conditions. Uterine PLA₂ activity showed a 167-fold increase in ovariectomized rats bearing estradiol-17 β (E₂)-implants as compared to those treated with vehicle only. On the other hand, dexamenthasone treatment reduced the E₂-stimulable PLA₂ activity by about 24-fold. The uterine PLA₂ activity in the ovariectomized rat uterus was low and not altered by instillation of progesterone (P₄) implants or by administration of dexamethasiome. On the contrary, simultaneously placement of E₂- and P₄-implants prevented significantly the rise in PLA₂ activity as observed under upposed E₂ exposure. Dexamethasome treatment further reduced the activity. The endogenous concentration of uterine PGF was several fold higher in the E₂-implanted ovariectomized rats as compared to those without the E₂-implants or carrying only P₄-implants. The simulataneous treatment of the E₂-implanted rats with P₄ and/or dexamethasone reduced the uterine PGF concentrations considerably. The uterine PGF concentration was always lower in the ovariectomized rats under any condition if they were not treated with E₂. Uterine PGE-A concentration did not change significantly between the ovariectomized rats and the ovariectimized rats carrying E₂-implants. The treatment with P₄ and/or dexamethasome, however, tended to decrease the PGE-A concentration. The production of PGF by the uterine homogenate increased by several fold in ovariectomized rats implanted with E₂-silastic capsules as compared to those without the e₂ implants. The treatments of the E₂-implanted rats with P₄ or dexamethasome did not alter this production. However, simultaneous exposure of E₂-implanted rats to P₄ and dexamethasone lowered the production rate of PGF in the uterus. The treatment of the ovariectomized rats with dexanethasome or P₄ tended to elevate the uterine PGF production. The uterine PGE-A production followed more or less the same pattern. The analysis of our present data suggest that although a relationship exists between uterine PLA₂ activity and PGD concentration, the role of PG synthetase could also be important in regulating PGF synthesis. Our study with dexamethasome, which showed inhibition of uterine PLA₂ activity and decline in endogenous but not $\text{in vitro}$ production of PGs, indicate that cellular integrity is essential for PLA₂ of function as a rate-limiting step in PG synthesis. The present findings also imply that alteration in PLA₂ or PG synthesis has little influence on PGE formation and the latter is not sensitive, to any great extent, to steroid hormonal changes. We considere that fluctuation in PGF/PGE ratio is mainly due to fluctuation in PGF level under various conditions.     

Uterine and placental prostaglandins and their modulation of oxytocin sensitivity and contractility in the parturient uterus

The parturient uterus develops a markedly enhanced sensitivity to the uterotonic action of oxytocin (OT). The mechanism leading to this enhanced OT sensitivity is not known. Our previous work suggested that prostaglandins (PGs) may be involved. To define the relationship between OT sensitivity and uterine PG production, we measured uterine sensitivity to OT by a quantitative dose-response procedure in rats on Days 19, 20, 21 and 22 of pregnancy and monitored uterine and placental tissue concentrations of PGF2 alpha and PGE2. In addition, we determined the effects of inhibition of endogenous PG synthesis on OT sensitivity and uterine contractility. We found that both OT sensitivity and spontaneous contractility are positively related to uterine PGF2 alpha production. An abrupt increase in OT sensitivity was observed on Days 21 and 22 of pregnancy. The increase in OT sensitivity was coincidental with the marked increase in PGF2 alpha production in the uterus on Days 21 and 22 of pregnancy. Suppression of in vivo PG synthesis caused a reduction in both spontaneous uterine contractility and OT-induced contractions. Uterine PGE2 concentrations and release were 3-5 times lower than PGF2 alpha. There were no significant fluctuations of uterine PGE2 concentration measured on these last 4 days of gestation. Placental PG levels were also found not to be related to uterine contractility. Placental PGE2 levels were higher than PGF2 alpha and may play a regulatory role in placental perfusion. However, placental PGs did not vary with gestational age.     

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)     

A novel anti-lipolytic action of norepinephrine in uteri isolated from spayed rats appears subserved by the activation of alpha 1-adrenoreceptors diminishing the generation and release of lipolytic prostaglandins

The effects of norepinephrine (NE: 3 x 10(-6) M) on the outputs of prostaglandins (PGs) E1, E2 and F2 alpha, from uterine horns isolated from ovariectomized rats and suspended in solutions with or without exogenous glucose, were explored. The releases of the different PGs into the external medium were determined after incubating for one hour uterine preparations, mounted within a tissue bath and receiving a constant preload tension. In glucose-containing solutions, NE enhanced the basal output of PGE2 and failed to alter the basal releases of PGE1 or of PGF2 alpha. In glucose-free media, the basal output of PGE2 was comparable to that detected in presence of exogenous glucose, and its augmentation following added NE was again evident. However, the basal outputs of PGE1 and of PGF2 alpha, greater in glucose-free solutions than in glucose-containing media, were significantly diminished by added NE. Uterine triglyceride (TG) levels were also explored, both immediately after sacrifice (0 min) or following suspending uterine segments during one hour (60 min) in solutions containing exogenous glucose or not. In glucose-containing media, tissue TGs did not differ at 0 min or at 60 min, neither in controls, nor in NE-challenged preparations, whereas in glucose-free solutions, TGs were significantly smaller at 60 min than at 0. interestingly, the addition of NE completely prevented the dimunition of uterine TGs, present at 60 min in glucose-free medium. Neither propranolol nor yohimbine (10(-6) M) altered this sparing action of added NE on tissue TGs, but phentolamine or prazocin (10(-6) M), effectively antagonized the preventive effect of the agonist.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of uterine luminal perfusion of PGF2α and PGE2 on uterine vasomotor response and PGF2α output in cyclic cattle

Six cyclic Holstein dairy cows were anesthetized on days 12–14 post-oestrus. Reproductive tract was exposed by midventral incision, and the ovarian (utero-ovarian) vein and facial artery cannulated. Oviduct was ligated, and a catheter (affluent) introduced into the tip of the uterine horn. The uterine horn was ligated above the uterine body, a second catheter (effluent) introduced into the uterine lumen, and an electromagnetic blood flow transducer placed around the uterine artery. On the day following surgery, the uterine horn was infused constantly for 9 h with PGF_2α dissolved in PBS (0.7 ml/min, 177 ng/ml). During periods 1 and 3 (first 3 h and last 3 h, respectively) only PGF_2α was perfused; during period 2 (between 3 h and 6 h) 101tgμg/ml of PGE₂ were added to the perfusate together with PGF_2α. Uterine venous and peripheral blood samples were collected simultaneously every 15 min, and uterine blood flow recorded continuously. Least-square means for PGF measured in uterine venous drainage for periods 1, 2 and 3 were 315 ± 26, 557 ± 24 and 511 ± 26 pg/ml, respectively (P < 0.05). Uterine blood flow values were 52 ± 5, 67 ± 4 and 61 ± 4 ml/min for periods 1, 2 and 3 (P < 0.08), respectively.Results do not support the hypothesis that the antiluteolytic effect of PGE₂ is associated with a suppression of uterine PGF_2α release into the circulation. Greater release of PGF to the circulation in period 2 (addition of PGE₂) is probably the result of the vasodilatory effect of PGE₂ on uterine endometrial vasculature.     

Follicular and uterine prostaglandin levels in relation to uterine contraction and the first ovulation of a sequence in the hen

Changes in the concentration of progesterone, estrone, estradiol, prostaglandins (PG) E2, 6-keto F1 alpha and 13,14-dihydro-15-keto F2 alpha (PGFM) were measured in peripheral plasma, and in venous effluent from the shell gland and the largest (F1) and the second largest (F2) preovulatory follicles. Tissue concentrations in the F1, F2 and the most recently ruptured follicle and the shell gland also were determined. Changes in these criteria were compared to changes in uterine contraction before the first ovulation of a sequence. Significant increases of PGF2 alpha and PGFM in the peripheral plasma were observed when the frequency of uterine contraction reached a maximum, about 1 h before ovulation. Relative to peripheral plasma, the concentrations in F1 plasma of progesterone, PGF2 alpha and PGFM were increased 20-fold, 150-fold and 15-fold, respectively, at the time of the maximum frequency of uterine contraction. The highest tissue concentrations of PGs were also observed in the F1 follicle. These results suggest that the largest preovulatory follicle is the major source of PG synthesis and release. These PGs may stimulate uterine contraction and may also play a role in follicular rupture and release of the ovum.     

Differential production of PGF and 6-keto-PGF1α by the rat endometrium and myometrium in response to oxytocin, catecholamines and calcium ionophore

Uterine horns from castrated, estrogen-treated rats were superfused for 6 hours in 95% O₂/5% CO₂ at 37°C. The method of superfusion in which medium flows separately over the inner and outer surfaces of the horn allows prostaglandin synthesis in the myometrium and endometrium to be measured independently while their anatomical relationship is undisturbed. Prostaglandins were measured by radioimmunoassay. The myometrium formed more 6-keto-PGF_1α than PGF whereas the opposite was true of the endometrium. Production rates of TxB₂ in both tissues were relatively low. The addition of ionophore A-23187, oxytocin or phenylephrine to the superfusion medium not only increased the myometrial production rates of both 6-keto-PGF_1α and PGF but also increased the ratio 6-keto-PGF_1α:PGF. Neither ionophore nor phenylephrine affected the rate of prostaglandin synthesis in the endometrium whereas oxytocin caused a significant increase in the production rate of PGF. We conclude that the large amounts of 6-keto-PGF_1α in the myometrial superfusate probably originate in both the smooth-muscle cells of the myometrium and the endothelium of the myometrial blood vessels. The differential responses to ionophore A-23187, phenylephrine and oxytocin suggest differences in the mode of their regulation of prostaglandin synthesis.     

Prostaglandin mediated action of IUD's (II) F-prostaglandins (PGF) in the uterine horn of pregnant rats and hamsters with intrauterine devices

The present investigation clearly shows that the presence of an IUD is associated with uterine hypertrophy and an increased production of F-prostaglandins.In the hamster, a bilateral IUD produced a significant increase in peripheral plasma PGF, presumably of uterine origin and an increased uterine PGF content at 2230 – 2300 h of day 4 of pregnancy. Earlier sampling (1530 – 1600 h) on the same day of pregnancy did not reveal any significant difference.In the rat, uterine PGF content and concentration, as well as PGF levels in uterine venous plasma were all increased in the IUD bearing horn from day 4 pregnant animals at 1530 – 1630 h in comparison to the contralateral control horn.     

Effect of prostaglandin F2α on uterine or ovarian secretion of prostaglandins E and F2α in vivo in 90–100 day hysterectomized, intact or ovariectomized pregnant ewes

Vehicle or 8 or 16 mg of PGF_2α per 58 kg body weight was given intramuscularly to intact, hysterectomized or ovariectomized 90–100 day pregnant ewes in three separate experiments. Both doses of PGF_2α increased PGF_2α in ovarian venous plasma compared with controls at 72 hr post treatment in intact (P≤0.05) but did not in hysterectomized (P≥0.05) 90–100 day pregnant ewes. Concentrations of PGE in ovarian venous blood of intact ewes did not differ (P≥0.05) between treatment groups and were equivalent to concentrations of PGE determined in uterine venous plasma. PGE was decreased in ovarian venous plasma by PGF_2α in hysterectomized ewes (P≤0.07). PGE in uterine venous plasma averaged 6 ng/ml over the 72-hr treatment period in intact and ovariectomized 90–100 day pregnant ewes and was 12 fold greater (P≤0.05) than PGF_2α which averaged 500 pg/ml in uterine venous plasma. Both PGF_2α and PGE increased (P≤0.05) by 64 hr in uterine venous plasma of the 8 mg PGF_2α — treated intact pregnant ewes. A significant quadratic increase (P≤0.05) was observed for PGF_2α and PGE in the vehicle and both PGF_2α treatment groups of intact ewes at the end of the 72-hr sampling period. It is concluded that the uterus and ovaries secrete significant quantities of PGE but little PGF_2α during midgestation. In addition, PGF_2α increased uterine secretion of PGE . PGE may be a placental stimulator of ovine placental secretion of progesterone or PGE may protect placental steroidogenesis from actions of PGF_2α.     

Localization of prostaglandin F in the ovine uterus during early pregnancy

As part of a study on the anti-luteolytic action of the sheep conceptus, the distribution of prostaglandin F (PGF) within the uteri of 19 pregnant and 14 non-pregnant ewes was studied using three antisera to PGF_2α and fluorescent antibody tracing. In the uteri of seven non-pregnant ewes up to Day 11 after estrus (Day 0) and in uteri of $\text{18}\text{19}$ pregnant ewes up to Day 50, PGF was localized mainly in the lamina propria, with very little on epithelial cells lining the uterine lumen. After Day 11, in the uteri of seven non-pregnant ewes, PGF was localized on the surface of luminal epithelial cells and throughout their cytoplasm, and to a lesser extent in the lamina propria. The distribution of PGF on Days 14 and 17 in the gravid and non-gravid horns of the uteri of 13 ewes made unilaterally pregnant (conceptus confined to one uterine horn) was similar to that described above for normal pregnant and non-pregnant ewes after Day 11 respectively.These results are interpreted to indicate a change in the distribution of PGF in sheep uteri due to the presence of a conceptus.     

Effect of prostaglandin F2alpha (PGF2alpha), indomethacin, tamoxifen or estradiol-17beta on prostaglandin E (PGE), PGF2alpha and estradiol-17beta secretion in 88 to 90-day pregnant sheep

Treatment with PGF2alpha plus estradiol-17beta aborts 90-day pregnant ewes, whereas PGF2alpha or estradiol-17beta alone does not abort ewes. The objective of this experiment was to evaluate whether tamoxifen, an estrogen receptor antagonist, estradiol-17beta, prostaglandin F2alpha (PGF2alpha), indomethacin, or some of their interactions affected ovine uterine/placental secretion of PGF2alpha, estradiol-17beta or prostaglandins E (PGE), because a single treatment with PGF2alpha and estradiol-17beta given every 6 h aborts 90-day pregnant ewes. Concentrations of PGF2alpha in uterine venous blood were increased (P < or = 0.05) by estradiol-17beta, PGF2alpha + estradiol-17beta, and PGF2alpha + tamoxifen, and decreased (P < or = 0.05) by indomethacin or PGF2alpha + indomethacin at 72 h when compared to the 0 h samples. Concentrations of PGE in uterine venous blood were decreased (P < or = 0.05) by indomethacin and PGF2alpha + indomethacin and increased (P < or = 0.05) by PGF2alpha + estradiol-17beta at 72 h when compared to the 0 h samples. Concentrations of PGF2alpha in inferior vena cava blood at 6 h were increased (P < or = 0.05) by PGF2alpha either alone or in combination with indomethacin, tamoxifen, or estradiol-17beta, which is due to the PGF2alpha injected. Concentrations of PGF2alpha in inferior vena cava blood in PGF2alpha + estradiol-17beta-treated 88- to 90-day pregnant ewes increased (P < or = 0.05) linearly over the 72-h sampling period and averaged 4.0 + 0.4 ng/ml. Concentrations of PGF2alpha in inferior vena cava blood of control, PGF2alpha, tamoxifen, PGF2alpha + indomethacin, PGF2alpha + tamoxifen, and estradiol-17beta-treated ewes did not differ (P > or = 0.05) and averaged 0.4 + 0.04 ng/ml. Profiles of PGE in inferior vena cava blood of 88- to 90-day pregnant ewes treated with vehicle, PGF2alpha, estradiol-17beta, tamoxifen, tamoxifen + PGF2alpha, or estradiol-17beta + PGF2alpha did not differ (P > or = 0.05). Concentrations of PGE in inferior vena cava blood of 88- to 90-day pregnant ewes treated with indomethacin or PGF2alpha + indomethacin were lower (P < or = 0.05) than in control ewes. Concentrations of estradiol-17beta in jugular venous plasma of PGF2alpha + estradiol-17beta-treated 88- to 90-day pregnant ewes increased linearly and differed (P < or = 0.05) from controls. Profiles of estradiol-17beta in jugular venous plasma of PGF2alpha, indomethacin, tamoxifen, and PGF2alpha + tamoxifen and PGF2alpha + indomethacin, estradiol-17beta, and controls did not differ (P > or = 0.05). It is concluded that treatment with a single injection of PGF2alpha and estradiol-17beta given every 6 h causes a linear increase in PGF2alpha and estradiol-17beta.