Role of prostaglandin F2alpha in ovulation.

Using radioimmunoassay procedures, the levels of plasma, uterine and ovarian prostaglandin (PG) F2alpha, and those of plasma estradiol and progesterone were measured in intact, hysterectomized or ovariectomized immature female rats pretreated with PMS and subsequent HCG. Occurrence of ovulation was confirmed at 8 hours after the HCG administration not only in the intact rats but also in the hysterectomzied rats. The levels of plasma estradiol and progesterone, and of uterine and ovarian PGF2alpha rose with the PMS injection alone, but they did not reach the peaks before the HCG administration. Both plasma estradiol and uterine PGF2alpha showed a peak at 2 hours after the HCG injection. These peaks were antecedent 2 or 6 hours before the peaks of ovarian and plasma PGF2alpha, respectively. However, such increase of uterine PGF2alpha does not seem to be indispensable for ovulation, because ovulation could occur in the hysterectomized rats. The levels of ovarian PGF2alpha showed a high plateau from 4 to 8 hours after the HCG injection, and then rapidly decreased after ovulation. The levels of plasma PGF2alpha peaked not only in the intact rats but also in the hysterectomized rats at 8 hours after the HCG treatment. But in the ovariectomized rats, this plasma PGF2alpha peak at 8 hours disappeared and there was no statistical change of plasma PGF2alpha throughout the PMS-HCG treatment. Plasma progesterone gradually increased and reached the maximum at 10 hours after the HCG injection. These results conclude that the main source of increased plasma PGF2alpha during the ovulatory process induced with the PMS-HCG treatment is the ovary, and it is strongly suggested that a rapid increase of PGF2alpha in the ovary may play some important role(s) in the ovulatory process.     

Induction of luteolysis in mares by ultrasound-guided intraluteal treatment with PGF2alpha.

To evaluate the technique of ultrasound-guided luteal injection in mares, PGF2alpha was administered under ultrasound guidance to horse mares (n = 7 to 9 per group) on Day 9 postovulation via either a systemic (i.m.; zero, 0.01, 0.1, or 5 mg/dose) route or a local intraluteal (i.l.; zero, 0.01 or 0.1 mg/dose) route. The luteolytic efficacy of each treatment was determined based on post-treatment decreases in progesterone concentration, interval to uterine edema (IE) and interovulatory interval (IOI). Local administration of PGF2alpha directly into the CL consistently induced luteolysis, at doses up to 50-fold lower than the lowest effective systemic dose. Significant decreases in IOI and IE occurred in mares treated with 5 mg PGF2alpha i.m. or 0.1 mg PGF2alpha i.l., but did not occur in mares treated with 0.1 or 0.01 mg PGF2alpha i.m., 0.01 mg PGF i.l., vehicle i.l. or vehicle i.m.. Progesterone concentrations were reduced to less than 10% of pretreatment values by two days post treatment in mares treated with 5 mg PGF2alpha i.m. or 0.1 mg PGF2alpha i.l.. PGF2alpha doses of 0.1 mg i.m. and 0.01 mg i.l. were associated with smaller but significant progesterone decreases (to 66% and 46% of pre-treatment values, respectively) by two days post treatment. Progesterone values after administration of i.l. vehicle did not differ from pre-treatment values by two days post treatment, but were significantly lower (53% of pre-treatment values) by four days post treatment. Intramuscular treatment with vehicle or 0.01 mg of PGF2alpha did not significantly reduce progesterone concentrations below pretreatment values. Overall, the minimum effective luteolytic dose of PGF2alpha given intraluteally was between 0.01 and 0.1 mg. Based on the results of this study, ultrasound-guided i.l. injection appears to be a repeatable method for studying the direct effect of other chemicals on luteal function. However, the current procedure carries some risk, since three i.l. injections were associated with ovarian abscesses.     

Absence of uterokinetic effects of prostaglandin F 2 alpha on oxytocin-reactive uterus in the mare

In most cyclic females, prostaglandin F(2alpha) (PGF(2alpha)) triggers a uterine motility response resembling that of oxytocin (OT). To determine if PGF(2alpha) is a uterokinetic substance in the cycling mare, uterine motility was measured by intrauterine balloon technique in 12 conscious, normally cyclic mares. After 60 min of saline infusion, continuous intravenous (i.v.) infusion with OT (1 i.u./min) was followed by PGF(2alpha) (200 mug/min) for 60 min each. The experiment was repeated 3 wk later except with PGF(2alpha) preceeding OT. A second group of mares was administered OT (60 i.u.) either i.v., intramuscularly (i.m.), or intrauterinely (i.u.). Plasma samples were studied for progesterone concentration. Control uterine motility for the first group of mares was (mean +/- SEM) 545.83 +/- 45.10 mm(2). Significant (P<0.05) elevation in uterine motility was recorded for OT (1118.60 +/- 70.56 mm(2)) regardless if PGF(2alpha) preceded OT infusion or vice-versa. No significant difference (P>0.05) was seen in motility after PGF(2alpha) (423.33 +/- 31.12 mm(2)) infusion. The uterokinetic effect of OT was greatest when OT was administered i.v. (1696.50 +/- 195.46 mm(2)) followed by i.m. (819.82 +/- 39.96 mm(2)), and it was least effective when administered i.u. (607.83 +/- 21.56 mm(2)) as compared to control uterine motility (279.78 +/- 22.33 mm(2)). Skin electrical resistance values rose from 0 to 2000 ohms with PGF(2alpha) infusion (but not with OT), indicating that PGF(2alpha) was bioactive. It was concluded that PGF(2alpha) was not a uterokinetic substance in the cyclic mare.     

The effects of ovarian steroids in controlling rat uterine prostaglandin F2-alpha during the peri-implantation period

Rats with delayed implantation, induced by ovariectomy or hypophysectomy, as well as those with normal pregnancy were used to examine the changes in uterine prostaglandin F2 alpha (PGF2 alpha) associated with implantation. In normal pregnant rats, while maximal uterine production of PGF2 alpha was found at 09:00, maximal catabolic enzyme activity (CEA) was seen at 17:00 of day 4. Uterine content of PGF2 alpha was high at 17:00 of day 4, but decreased by 80% within the next 24 h. There was no change in PGF2 alpha production during the first 6 h after injection of estradiol to hypophysectomized animals. There was, however, a dramatic decrease in production within the next 6 h. In contrast, CEA was not different in animals treated with estrogen than in those receiving only progesterone. In ovariectomized animals, uterine PGF2 alpha production also was lowered by estrogen but in these animals CEA was significantly elevated 18 h after injection of estradiol. Estrogen caused a greater increase in PGF2 alpha content in the hypophysectomized, compared to the ovariectomized, rats. The results are consistent with the view that ovarian steroids play an important role in controlling the changes in uterine PGF2 alpha around the time of implantation in rat.     

The use of catheter-tipped pressure transducers for chronic measurement of genital tract pressures in the ewe. II. Effects of oxytocin and prostaglandin F(2)alpha

Chronic catheterisation of the uterus, ampulla, and abdomen was performed in five ewes using solid-state, catheter-tipped pressure transducers. The catheters remained in place for up to 129 d, allowing in vivo studies of the effects of oxytocin and prostaglandin F(2)alpha (PGF(2)alpha). These agents did not produce any measurable increase in abdominal pressure. Intravenous (i.v.) oxytocin elicited a rapid increase in work done by both the uterus and ampulla. Intramuscular (i.m.) PGF(2)alpha produced a delayed uterine response but little change in the ampulla; i.v. PGF(2)alpha produced a rapid response at both sites. Low plasma progesterone concentrations (< 0.5 ng/ml) were associated with a greater uterine and ampullary response to oxytocin and with an enhanced uterine response to PGF(2)alpha. However, the uterine tube response to intravenous PGF(2)alpha was greatest when plasma progesterone concentrations were high.     

Differential effects of progesterone treatment on the oxytocin-induced prostaglandin F2 alpha response and the levels of endometrial oxytocin receptors in ovariectomized ewes.

The oxytocin-induced uterine prostaglandin (PG) F2 alpha response and the levels of endometrial oxytocin receptors were measured in ovariectomized ewes after they had been given steroid pretreatment (SP) with progesterone and estrogen to induce estrus (day of expected estrus = Day 0) and had subsequently been treated with progesterone over Days 1-12 and/or PGF2 alpha over Days 10-12 postestrus. The uterine PGF2 alpha response was measured after an i.v. injection of 10 IU oxytocin on Days 13 and 14, using the PGF2 alpha metabolite, 13,14-dihydro-15-keto-PGF2 alpha (PGFM), as an indicator for PGF2 alpha release. The levels of oxytocin receptors in the endometrium were measured on Day 14. During the treatment with progesterone, the peripheral progesterone concentrations were elevated and remained above 1.8 ng/ml until the morning of Day 14. The PGFM responses to oxytocin in untreated controls and SP controls were low on both Days 13 and 14 whereas the levels of endometrial oxytocin receptors in the same ewes were high. Treatment with progesterone either alone or in combination with PGF2 alpha significantly (p less than 0.04) increased the PGFM response on Day 14 and reduced the levels of endometrial oxytocin receptors; treatment with PGF2 alpha alone had no effect. It is concluded that progesterone promotes the PGFM response to oxytocin while simultaneously suppressing the levels of endometrial oxytocin receptors. PGF2 alpha treatment had no effect on either the uterine secretory response to oxytocin or the levels of oxytocin receptors in the endometrium.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of intramyometrial injection of prostaglandin F2α on severe post-partum hemorrhage

Effectiveness of prostaglandin F₂α (PGF₂α) in controlling post-partum uterine hemorrhage was evaluated with the following results.

1. Systemic administration, whether by continuous i.v. infusion or by gluteal i.m. injection, was not a completely adequate method for hemostasis.

2. Local administration by directly injecting into the uterine musculature, whether transabdominally or transvaginally, resulted in a dramatic reduction of the rate of bleeding.

Routine clinical application of the direct intramyometrial injection of PGF₂α for severe post-partum hemorrhage is recommended in view of its easy performance, excellent hemostatic effect, minimal side effects and good prognosis.     

Uterine secretion of prostaglandin F2 alpha in response to oxytocin in ewes: changes during the estrous cycle and early pregnancy.

Experiment 1 was conducted to determine when the ovine uterus develops the ability to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin and how development is affected by pregnancy. Pregnant and nonpregnant ewes received an injection of oxytocin (10 IU, i.v.) on Day 10, 13, or 16 postestrus. Jugular venous blood samples were collected for 2 h after injection for quantification of 13,14-dihydro-15-keto-PGF2 alpha (PGFM). In nonpregnant ewes, concentrations of PGFM increased following oxytocin on Day 16 but not on Day 10 or 13. Concentrations of PGFM did not increase following treatment on Day 10, 13, or 16 in pregnant ewes. Therefore, the ability of oxytocin to induce uterine secretion of PGF2 alpha develops after Day 13 in nonpregnant but not in pregnant ewes. Experiment 2 was conducted to precisely define when uterine secretory responsiveness to oxytocin develops. Pregnant and nonpregnant ewes received oxytocin on Day 12, 13, 14, or 15. In nonpregnant ewes, concentrations of PGFM increased following treatment on Days 14 and 15, but not earlier. Peripheral concentrations of progesterone showed that uterine secretory responsiveness to oxytocin developed prior to the onset of luteal regression. As in experiment 1, the increase in concentrations of PGFM following administration of oxytocin was much lower in pregnant than in nonpregnant ewes; however, some pregnant ewes did respond to oxytocin with an increase in PGFM. In experiment 3, pregnant ewes received an injection of oxytocin on Day 18, 24, or 30 postmating. Concentrations of PGFM increased following oxytocin on Days 18 and 24. The conceptus appears to delay and attenuate the development of uterine secretory responsiveness to oxytocin.     

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.     

Effects of gonadotropin releasing hormone and prostaglandin F(2)alpha on the reproductive performance in postpartum cows

A study was conducted to determine whether treatment with gonadotropin releasing hormone (GnRH) in combination with prostaglandin F(2)alpha (PGF(2)alpha) could enhance ovarian activity and uterine involution in postpartum dairy cows to reduce the calving interval. Cows were randomly assigned to one of three treatment groups. Cows (n = 8) in Group 1 received 100 mug GnRH intramuscularly (i.m.) twice on Day 20 and Day 35 postpartum, and 25 mg PGF(2)alpha i.m. on Day 47 postpartum. Group 2 (n = 8) received a single i.m. injection of 100 mug GnRH on Day 25 postpartum and 25 mg PGF(2)alpha i.m. on Day 37 postpartum. The Control Group (n = 9) did not receive hormonal treatment. Palpation per rectum of the reproductive organs and serum progesterone (P) determination were performed twice a week to monitor ovarian activity and uterine involution. Postpartum interval to the first ovulation was short in treated groups (Group 1, 21.0 d; Group 2, 26.3 d) compared with Control Group (30.1 d, P < 0.05). Likewise, mean frequency of ovulation was increased in both treated groups compared with the Control Group (P < 0.05). Cows in treated groups required fewer days to complete uterine involution than in the Control Group. The mean interval to the first service, the conception rate at first service and the number of services per conception showed no significant differences among the three groups, but the mean days from calving to conception were shorter for the treated groups (78.7 d in Group 1; 83.3 d in Group 2) than (109.1 d, P < 0.05) for the Control Group. Our results suggest that combined treatment with GnRH and PGF(2)alpha may enhance ovarian activity in the postpartum cow, resulting in improved reproductive performance.     

The effect of prostaglandins F2 alpha and E2 on the adrenergic activity of the uterus of laying hens (Gallus domesticus) in vitro

The effect of PGF2 alpha and PGE2 before or after administration of isoproterenol or norepinephrine was studied on uterine strips of White Leghorn laying hens. Prostaglandins (0.2 ng/ml of bath solution) always produced an increase in tension and area under the tracing, the effect of PGF2 alpha being significantly marked especially when administered after norepinephrine. Norepinephrine and isoproterenol (0.1 microgram/ml of bath solution) produced a marked decrease in area under the tracing, the effect of isoproterenol being more potent especially when administered before prostaglandins.     

Changes in plasma concentrations of arginine vasotocin after intrauterine injections of prostaglandin F-2 alpha and acetylcholine at various times during the oviposition cycle of the domestic hen (Gallus domesticus)

Prostaglandin F-2 alpha (PGF-2 alpha, 1 microgram) and acetylcholine (10 mg) were injected into the uterus of chickens 23, 21, 16, 8 or 4 h before expected oviposition. Plasma concentrations of immunoreactive arginine vasotocin and PGF were measured in relation to the time of administration of PGF-2 alpha or acetylcholine or to the premature oviposition that was induced. PGF-2 alpha or acetylcholine administration caused premature oviposition and a marked increase in plasma arginine vasotocin levels only when an egg was present in the uterus. Changes in plasma PGF concentrations were not observed. After premature oviposition was induced, plasma values of PGF and arginine vasotocin increased at the expected time of oviposition. Manual stimulation of the uterus 4 h after oviposition also stimulated arginine vasotocin release. During spontaneous oviposition, a rise in plasma PGF concentration preceded increases in uterine contractility and plasma arginine vasotocin concentration. These results suggest that PGF may stimulate uterine contractility which in turn causes the release of arginine vasotocin to provide an additional contractile stimulus during oviposition.     

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.     

Inhibition of uterine prostaglandin-F2 alpha production by bovine conceptus secretory proteins

The effect of bovine conceptus secretory proteins (CSP) on uterine prostaglandin (PG)-F2 alpha production was evaluated in dairy cattle following injection of estradiol-17 beta. Intrauterine injections of dialyzed serum proteins (Control, n = 5) or CSP (n = 5) were administered from days 15 through 18 post-estrus. Following intrauterine treatments on day 18, all cows were injected with E2 (3 mg) to stimulate uterine PGF2 alpha production. Plasma concentrations of progesterone (P4) and 15-keto-13,14-dihydro-PGF2 alpha (PGFM) were determined by RIA. The PGFM responses following E2 challenge were decreased (p less than 0.01) for cows receiving CSP versus serum proteins into the uterine lumen. Individual PGFM, P4 and cycle length responses are discussed. Data suggest that proteins secreted by the bovine conceptus suppress uterine PGF2 alpha production during pregnancy recognition in the cow.     

Direct evidence for the involvement of prostaglandin F2 alpha in the first step of estrone-induced blastocyst implantation in the spayed rat.

The effect of prostaglandin F2 alpha (PGF2 alpha) on blastocyst implantation in spayed rats has been studied. In preliminary experiments, the first implantation sites were observed 8 - 12 hours after a single injection of estrone in ovariectomized and progesterone-conditioned rats. Intraluminal instillation of PGF2 alpha into the right uterine horn 8 - 10 h after the estrone injection increased the number of implantation sites. Even treatment with PGF2 alpha without previous estrone injection induced the first step of blastocyst implantation as shown by uterine dye site reaction (Niagara-blue test). The results are discussed with regard to the possible role of PGF2 alpha in the regulation of the blastocyst implantation processes in the rat.     

Effect of oxytocin on concentration of PGF2 alpha in the uterine lumen and subsequent endometrial responsiveness to oxytocin in pigs

The aim of this study was to determine the effect of oxytocin on PGF2 alpha secretion into the uterine lumen of pigs and subsequent endometrial responsiveness to oxytocin in vitro. Cyclic, pregnant and oestradiol-induced pseudopregnant gilts were injected i.v. with vehicle or 20 iu oxytocin 10 min before hysterectomy on day 16 after oestrus. Concentrations of PGF2 alpha and 13,14-dihydro-15-keto PGF2 alpha (PGFM) were significantly increased in uterine flushings collected at hysterectomy (P < 0.05) in pregnant oxytocin-injected gilts. Concentrations of PGF2 alpha and PGFM were greater (P < 0.001) in pregnant than in pseudopregnant and cyclic gilts, and greater (P < 0.01) in pseudopregnant than in cyclic gilts. The ratio of PGFM:PGF2 alpha tended to be greater in cyclic (P < 0.06) and pseudopregnant gilts (P < 0.1) than in pregnant gilts. At 85 +/- 5 min after oxytocin injection, endometrium from each gilt was incubated for 3 h for determination of phosphoinositide hydrolysis and PGF2 alpha secretion in response to treatment with 0 or 100 nmol oxytocin l-1. Endometrial phosphoinositide hydrolysis in response to 100 nmol oxytocin l-1 in vitro was greater (P < 0.05) in cyclic oxytocin-injected gilts than in cyclic vehicle-injected gilts. Treatment with oxytocin in vitro did not stimulate phosphoinositide hydrolysis significantly in vehicle- or oxytocin-injected pregnant gilts or pseudopregnant gilts. Endometrial PGF2 alpha secretion increased after treatment with 100 nmol oxytocin l-1 in vitro in cyclic vehicle-injected (P < 0.01), cyclic oxytocin-injected (P < 0.01), pregnant vehicle-injected (P = 0.06), pseudopregnant vehicle-injected (P < 0.05) and pseudopregnant oxytocin-injected (P < 0.05) gilts, but not in pregnant oxytocin-injected gilts. The increase in PGF2 alpha in pseudopregnant oxytocin-injected gilts was less (P < 0.05) than that in cyclic oxytocin-injected gilts. These results indicate that oxytocin increases the concentration of PGF2 alpha and PGFM in the uterine lumen during pregnancy and may upregulate endometrial responsiveness to oxytocin during late dioestrus in pigs, but does not have the latter effect during early pregnancy or oestradiol-induced pseudopregnancy.     

Response of the midpregnant human uterus to systemic administration of 15(S)-15-methyl-prostaglandin F2alpha

The contractile response of the midpregnant human uterus to a new (PG) prostaglandin analogue, 15(S)-methyl-PGF2alpha (15-me-PGF2alpha), was investigated and compared to the effect of natural PGF2alpha. It was found that the threshold dose of 15-me-PGF2alpha was around 10 mcg when given as a single intravenous injection, which is approximately 1/10 of the corresponding dose of PGF2alpha. It was also found that higher intravenous doses of 15-me-PGFalpha resulted in a uterine response of longer duration than that following PGF2alpha. Intramuscular injection of the analogue at doses of 1.0-1.5 mg induced a marked uterine stimulation sustained for 5-7 hours without causing local reaction. Intravenous infusion of 5 mcg/min of 15-me-PGF2alpha stimulated a level of uterine activity equivalent to that of 75 mcg/min of PGF1alpha. The incidence of gastrointestinal side effects was the same in the 2 treatment groups. However, there seemed to be a tendency toward a significantly higher abortion rate with the analogue.     

Increases in the oxytocin-induced prostaglandin F2 alpha response and reduction in the concentrations of endometrial oxytocin receptors in ewes in response to progesterone.

Ovariectomized ewes were given progesterone and oestrogen priming as steroid pretreatment and subsequently treated with progesterone, prostaglandin F2 alpha (PGF2 alpha), or both. In Expt 1, plasma concentrations of the metabolite 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured after an i.v. injection of oxytocin. There was little PGFM response in the untreated control ewes or in the pretreated ewes. Treatment with PGF2 alpha alone had no effect (P greater than 0.05), whereas treatment with progesterone either alone or with PGF2 alpha significantly (P less than 0.05) increased the uterine PGFM response to oxytocin. In Expt 2, chronically ovariectomized ewes had high concentrations of endometrial oxytocin receptors. Treatment with PGF2 alpha alone did not alter the concentrations of the receptors. Treatment with progesterone either alone or with PGF2 alpha significantly (P less than 0.05) reduced the concentrations of the receptors. It is concluded that progesterone promotes the PGFM response to oxytocin, but simultaneously suppresses the concentrations of endometrial oxytocin receptors.     

Uterine prostaglandin and blood flow responses to estradiol-17 beta in cyclic cattle

Normal cyclic dairy cattle (n = 7) underwent a midventral laparotomy on day 17 of the estrous cycle and were fitted, ipsilateral to the CL, with: an electromagnetic flow transducer around the uterine artery (UA; n = 5); catheters within the ovarian vein (OV; n = 7) via a uterine branch of the ovarian vein, uterine branch of the ovarian artery (UBOA; n = 5) and facial artery (FA; n = 7). On day 18, blood samples were collected at 30 min intervals for 1 h prior to injection of estradiol-17 beta (E2; 3 mg) and 12 h post-E2. Uterine blood flow (UBF) was monitored continuously and plasma samples analyzed for PGF2 alpha and PGFM. Exact locations of catheters in reproductive tracts were verified post-slaughter. Data were analyzed by method of least squares analysis of variance. Uterine blood flow (ml/min) increased above pre-E2 flow rates within 30 min post-E2 injection, peaked between 2.5 to 3.5 h and declined between 4 to 8.5 h. A small secondary rise in UBF occurred between 9 and 12 h. Regression analysis for concentrations (pg/ml) of PGF2 alpha and PGFM in the OV (i.e., [OV]-[FA]) demonstrate a similar response as PGFM concentration in the FA in that all increased at approximately 3 h, peaked between 5 and 7 h and returned to near baseline levels by 9 to 10 h post-E2. Facial artery PGFM concentrations were positively correlated with uterine production of PGF2 alpha (r = .66) and PGFM (r = .30), whereas FA PGF2 alpha concentrations were not. In three of five cows, a difference in PGF2 alpha was detected between UBOA and FA (UBOA greater than FA); supportive of a local countercurrent exchange between the uterine venous drainage and the ovarian artery.     

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)