Secretion rate of prostaglandin F during induced labor in goats.

Relationships between plasma flow and plasma concentrations of prostaglandin F were examined in the utero-ovarian veins of three pregnant goats. Plasma flow, measured by veno-arterial dilution of para-Aminohippurate in two goats, was unchanged or increased slightly when PGF concentrations were elvated by short-term infusions of PGF2alpha into a uterine vein. Utero-ovarian plasma flow was measured during labor in two goats. Flow doubled during advanced labor and then decreased sharply to very low rates during the terminal expulsive phase of stage II labor. A total of 8.3 and 9.5 mg PGF was released into the utero-ovarian vein of two goats during the last 6 hours before fetal delivery and maximal release rates of approximately 100 ug. min-1 were obtained some 5-10 minutes before delivery was completed. The highest plasma concentrations of PGF were detected immediately after completion of fetal delivery when utero-ovarian plasma flows were lowest.     

Production of prostaglandin Fα in ewes following luteal regression induced with a prostaglandin analogue, Estrumate (cloprostenol; I.C.I. 80996)

A single injection (100μg i.m.) of Estrumate (I.C.I. 80996) was used to induce luteal regression on day 8 of the estrous cycle in 3 sheep. Progesterone levels in the utero-ovarian vein and femoral artery had fallen within 6 h to <50% of the concentrations seen before injection of the analogue. Luteolysis was not associated with endogenous production of PGF. The concentration of PGF in the utero-ovarian vein began to increase 27–39 h after the administration of Estrumate, reaching a mean maximum concentration of 1455pg/ml 48 h after Estrumate. The mean concentration of PGF in the utero-ovarian vein between 36–69 h after Estrumate was significantly greater than during the 24 h before Estrumate (control period) or during the 0–30 h immediately after injection (both P < 0.001). The maximum secretion of estradiol and the pre-ovulatory LH peak occurred during the period of elevated PGF concentrations in the utero-ovarian veins. The possible importance of endogenous PGF production at this time is discussed.     

Stimulation by oxytocin of prostaglandin F levels in uterine venous effluent in pregnant and puerperal sheep

The purpose of this work was to investigate the effect of oxytocin on prostaglandin F (PGF) concentrations in uterine venous effluent. PGF was measured in utero-ovarian venous plasma from three pregnant ewes and in posterior vena caval plasma, from two puerperal ewes, during oxytocin administration. Oxytocin caused 4.9 – 5.3-fold increases in PGF concentrations in the pregnant animals, the response increasing towards term. In the puerperal animals oxytocin caused 3.7 – 17.2-fold increases in PGF concentrations with a marked latency in the response. Measurement of uterine activity and progesterone and total unconjugated oestrogen concentrations indicated that neither uterine contractions nor a decreased uterine blood flow accounted for the elevated PGF levels stimulated by oxytocin.     

A study of prostaglandin F2α as the luteolysin in swine: III effects of estradiol valerate on prostaglandin F, progestins, estrone and estradiol concentrations in the utero-ovarian vein of nonpregnant gilts

Polyvinyl catheters were placed into the right and left utero-ovarian veins and saphenous vein and artery of three control (C) and four estradiol valerate (EV) treated gilts on Day 9 after onset of estrus. The EV treated gilts received 5mg EV/day on Days 11 through 15 after onset of estrus. On Days 12 through 17 utero-ovarian vein blood samples were collected at 15 min intervals from 0700 to 1000 hr and 1900 to 2200 hr and single samples were taken at 1100 and 2300 hr. Peripheral blood samples (saphenous vein or artery) were taken at 0700, 1100, 1900 and 2300 hr from Day 12 until the control gilts returned to estrus or until Day 25 for EV treated gilts and used to measure plasma steroid hormone concentrations. Utero-ovarian vein prostaglandin F (PGF) concentrations (ng/ml, n=1,177) were measured by RIA. Status (control EV treated gilts) by day interactions were detected (P=.10). Curvilinear day trends were detected for plasma PGF concentrations in control (P<.01) but not EV treated gilts. PGF concentrations ( ) for control and EV treated gilts were 1.20 ± 2.08 and .26 ± .84 ng/ml, respectively. PGF peaks (concentrations greater than + 2 S.D.) occured with greater frequency in control gilts (X² = 4.87; P<.05). The interestrus interval ( ) for control and treated gilts was 19.0 ± .6 and 146.5 ± 74.8 days, respectively. Data indicate that estradiol valerate may exert its luteotrophic effect by preventing PGF release from the uterus.     

The biological meaning of prostaglandin-levels

Two groups of term pregnant rats, one pretreated with progesterone (P) and another with vehicle only, were induced to deliver with PGF2α. Through an implanted intrauterine (extraovular) catheter 5 μg PGF2α was injected into each animal every 15 minutes until delivery occurred. If induction failed the fetuses were removed by hysterotomy. All vehicle controls started delivery within 38.3±11.7 minutes. In contrast, none of the P-treated rats responded to PGF2α. In all animals uterine vein blood and uterine tissue were collected during labor.Measurements of the P and PGF in uterine vein plasma and uterine tissue showed that the P-treated rats had significantly higher P-levels than the controls (P<0.001). In contrast, the PGF-levels were similar in the two groups, but significantly elevated (P<0.001) beyond spontaneous labor values. Evidently, the massive elevation of PGF-levels only induces labor when the myometrial action of P is critically reduced and is ineffective when P-action is sustained. Thus, PGF-concentrations cannot be presumed to predict PGF-effect, because the latter is controlled by P.     

A study of prostaglandin F2α as the luteolysin in swine: II characterization and comparison of prostaglandin F, estrogens and progestin concentrations in utero-ovarian vein plasma of nonpregnant and pregnant gilts

Polyvinyl catheters were inserted into the right and left utero-ovarian veins (UOV) and saphenous vein (SV) and artery (SA)_of six nonpregnant (O) and five pregnant (P) gilts on day 11 after onset of estrus. Beginning on day 12, UOV blood samples were collected at 15-min intervals from 0800 to 1100 hr and 2000 to 2300 hr, and single samples were taken at 1200 and 2400 hrs. Peripheral blood (SA or SV) was sampled at 0800, 1200, 2000 and 2400 hr until gilts returned to estrus ( ) or day 24 or pregnancy. UOV plasma PGF concentrations (ng/ml; n = 1929) were measured by RIA. Status (P O) by day interactions were detected (P<.01) but variances among treatments were heterogenous (P<.01). Cuvilinear day trends were detected for PGF in 0 gilts (P<.01) but not P gilts. PGF peaks, defined as concentrations greater than two SD above the mean concentration for each gilt, occurred with greater frequency ((ifχ² = 16.4; P>.01)) in 0 than P gilts; and mean peak levels ( ) were 5.0 ± .27 and 3.84 ± .13 ng/ml, respectively.Progesterone concentrations were maintaiend in pregnant pigs and were indicative of luteal maintenance. Systematic differences in day trends of utero-ovarian venous plasma estradiol were detected between O and P pigs. These differences may be of paramount physiological importance and are discussed.     

Fetal and maternal endocrine changes associated with parturition in the goat

In 4 goats maternal jugular plasma concentrations of progesterone started to decline before labor commenced, but levels remained elevated above basal concentrations throughout parturition. Fetal and maternal plasma concentrations of estrogen rose before and during labor, increasing markedly just prior to fetal delivery. Fetal carotid plasma glucocorticoid concentrations appeared to rise over the 5 days prior to parturition, but a significant increase was only noted during labor. Maternal plasma concentrations of glucocorticoids were significantly lower than fetal plasma concentrations of glucocorticoids. Estradiol-17α was the predominant estrogen in both fetal and maternal plasma, less estrone was detected and apparently little estradiol-17β was present.No good correlation was found between plasma progesterone or estrogen and parturient uterine activity; the latter lasted from 22 to 78 hours, with the most dramatic increase occurring close to delivery. It is probable that other agents are involved in controlling uterine activity during parturition in the goat.     

The biological meaning of progesterone levels

The effect of systematically delayed progesterone treatment was examined in 45 pregnant rats near term. Progesterone (P) and prostaglandin F (PGF) were measured in uterine vein plasma and uterine tissue before and during spontaneous labor or during prolonged pregnancy. Control animals exhibited the expected P-withdrawal (Pw) prior to spontaneous labor and properly time P-treatment predictably prevente Pw and labor. However, when P was administered 11.7 ± 2.8 hours (Mean ± S.E.) before spontaneous labor, the animals delivered normally despite increased plasma and tissue P-levels. These observations show that P-concentration can not be equated to P-action. Thus, when high P-levels are measured near term, as in parturient women, the biological ACTION of this hormone on uterine function should be cautiously interpreted.     

Peripheral plasma progesterone and utero-ovarian prostaglandin F concentrations in the cow around parturition

The concentration of prostaglandin F in utero-ovarian venous plasma and progesterone in jugular venous plasma were determined by radioimmunoassay in 3 cows over the last 2–3 weeks of gestation. Utero-ovarian prostaglandin F concentrations did not show any consistent pattern in two of three cows until 48–72 h before term when the levels rose sharply from 1 ng/ml to a maximum 4–9 ng/ml during labour. The concentration of progesterone in jugular venous plasma tended to fall gradually over the last 20 days of gestation with a further fall occurring 48-36 h before delivery.In two other cows at around 240 days of gestation the concentration of plasma progesterone in ovarian venous plasma was 50 to 150 times the concentration of progesterone in uterine or jugular venous plasma. It is concluded from these results that the ovaries are the major source of progesterone in cows during late pregnancy. The findings also suggest that prostaglandin F may be the luteolytic factor responsible for the sharp decline in plasma progesterone concentrations over the last 48-36 h preceding parturition.     

Influence of the estrous cycle and prostaglandins on utero-ovarian vein blood flow in the rat

The blood flow rate in the utero-ovarian vein (UOV) has been measured in adult female rats during the different phases of the estrous cycle. It was observed that the blood flow rate in the UOV is high at proestrus and at estrus and low during diestrus days 1 and 2. The intravenous injection of 10 μg PGF_2α or PGE₂ diminishes the blood flow rate in the UOV. The efficacy of the two PGs in reducing blood flow is different in the various phases of the estrous cycle, being maximal during the day of estrus.     

Prostaglandin F in the peripheral plasma of the rhesus monkey in normal pregnancy and after the administration of dexamethasone and PGF2α

The concentration of prostaglandin F (PGF) has been measured in the peripheral plasma of normal rhesus monkeys ( ) during the final third of gestation, and in monkeys treated with dexamethasone or PGF₂α after day 145 of pregnancy. Daily administration of PGF₂α (10–15 mg/day im) reliably induced abortion within 3–6 days. However, dexamethasone (8 mg/day im from day 145) had no effect on the length of gestation.The concentration of PGF in the femoral venous plasma of untreated or dexamethasone-treated monkeys was highly variable, both in serial samples taken from the same animal and in samples taken from different animals at the same time of gestation. There was no indication of an effect of dexamethasone treatment on the plasma PGF levels, nor did the concentration of PGF increase during late pregnancy before spontaneous parturition. These results show that the myometrium of the pregnant rhesus monkey is highly sensitive to exogenous PGF₂α during late gestation. However, a significant increase in the peripheral plasma concentration of PGF prior to the onset of labor was not observed.     

Influence of the estrous cycle and prostaglandins on utero-ovarian vein blood flow in the rat

The blood flow rate in the utero-ovarian vein (UOV) has been measured in adult female rats during the different phases of the estrous cycle. It was observed that the blood flow rate in the UOV is high at proestrus and at estrus and low during diestrus days 1 and 2. The intravenous injection of 10 μg PGF_2α or PGE₂ diminishes the blood flow rate in the UOV. The efficacy of the two PGs in reducing blood flow is different in the various phases of the estrous cycle, being maximal during the day of estrus.     

Uterine prostaglandin concentrations following fetal death in sheep

Concentrations of prostaglandin E (PGE), PGF and 6-oxo-PGF_1α (the hydrolytic product of PGI₂) were measured by radioimmunoassay (RIA) in myometrium, endometrium, cotyledons, amnion and chorioallantois taken from different uterine areas from chronically catheterized sheep bearing fetuses which had died 12–26 h previously (n=4) or 34–72 h previously (n=4). These two groups of animals were designated fetuses dead <30 h and >30 h respectively. The time of fetal death was assessed on the basis of fetal heart rate and blood gases. At the time of the tissue collection the ewes were between 123 and 130 days after mating. For comparative purposes, tissues also were collected from four sheep bearing live chronically catheterized fetuses at 130 days of gestation.For myometrium, concentration of PGF, PGE and 6-oxo-PGF_1α were significantly higher in sheep bearing dead fetuses, compared to those bearing live fetuses. Analysis of variance also showed a significant effect of uterine area on myometrial PGE concentrations, concentrations being higher in tubal areas than elsewhere. Concentrations of PGE, PGF and 6-oxo-PGF_1α were higher in endometrium taken from uteri containing dead fetuses. In cotyledons, concentrations of PGF and 6-oxo-PGF_1α but not PGE, were significant elevated following fetal death. Concentrations of 6-oxo-PGF_1α, but not PGE or PGF, were elevated in both chorioallantois and amnion of sheep bearing dead fetuses, compared to those bearing live fetuses. In association with elevated PG concentrations, there was a progressive increase in the frequency and maximum amplitude of uterine contractions. These results show that PG concetrations are elevated following fetal death in sheep, and suggest an association between elevated PG concentrations and delivery of the dead fetus.     

Progesterone, 20α-dihydroprogesterone and PGF; Interrelated hormonal changes during pseudo-pregnancy in the rat

Ovarian and uterine tissue concentrations of progesterone, 20α-dihydroprogesterone (20_αOHP) and prostaglandin F (PGF) were measured during hormonally-induced pseudopregnancy, as were plasma levels of progesterone and 20αOHP, in hysterectomised and sham-operated rats. Elevated levels of PGF in uterine and ovarian tissues were coincident with declining concentrations of progesterone and increasing concentrations of 20αOHP in the sham-operated rats. Maximum PGF concentrations were apparent in uterine tissue 14 days after hCG injection, coincident with the plasma, ovarian and uterine nadir concentrations of progesterone. A small but statistically significant increase in ovarian PGF was apparent at this time in sham-operated rats. This elevation of ovarian PGF was abolished by hysterectomy.     

Changes in the plasma prostaglandin F2 alpha metabolite before and during spontaneous labor and labor induced by amniotomy, oxytocin and prostaglandin E2

To elucidate the role of endogenous prostaglandin F2 alpha in spontaneous and induced labor, plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were determined before the onset of labor, at onset of labor, during active labor, at the crowning of the fetal head, and 1 and 2 hours after delivery. Patients in spontaneous labor and labor induced by amniotomy, oxytocin, and prostaglandin E2 were studied. The levels of plasma PGFM in patients who entered spontaneous labor fell 2 to 3 weeks before delivery, whereas those in the induced labor group did not change until the time of induction. Although the levels of PGFM rose gradually with the progress of labor in all cases, the levels in the spontaneous labor were significantly lower in each stage than in the corresponding stage of induced labor. These results suggest that endogenous prostaglandin F2 alpha (PGF2 alpha) production decreases 2-3 weeks prior to the spontaneous onset of labor and is increased again as labor progresses, that the patterns of PGF2 alpha production are similar to each other during spontaneous labor and labor induced by various methods. Therefore, it is felt that endogenous PGF2 alpha may participate in the progress of all kinds of labor.     

Secretion of oxytocin in pregnant and parturient cows: corpus luteum may contribute to plasma oxytocin at term

Plasma oxytocin (OT) concentrations were determined in 14 late-pregnant and parturient Angus-Hereford cows. Jugular and utero-ovarian veins were cannulated for simultaneous withdrawal of blood samples. Samples were collected at 10-min intervals for 6 h once weekly beginning 60-14 days before the date of expected delivery (group 1), or daily 3-7 days before the due date (group 2). In a third group, samples were collected at 15-min intervals every other day for 12 h beginning 1 wk before calving. Basal levels of OT were low, the overall mean for both veins was 0.46 +/- 0.03 microU/ml until a week before parturition, and then increased to 0.77 +/- 0.1 microU/ml (P < 0.02). Spurts of OT occurred intermittently on all days. Interpeak intervals averaged 71.0 +/- 10.7 min until Day -14, and from Day -14 to Day -1 the intervals were 44.0 +/- 5.3 min (P < 0.05). From Day -60 to Day -25 the amplitudes of OT peaks were low and similar in both veins (mean 1.37 +/- 0.1 microU/ml). From Day -14 to Day -1 the peak amplitudes were 3.6 +/- 0.4 microU/ml on average (P < 0.02). During the last 2 wk the utero-ovarian peak of OT was frequently higher than the peripheral peak. In addition, a number of spurts were observed in the utero-ovarian vein only (solo peaks). On the day of parturition during the first stage of labor, peak amplitudes had increased to 7.3 +/- 2.0 microU/ml, and the interpeak intervals had become shorter than before labor (mean 25.1 +/- 2.6 min). A large surge of OT initiated the expulsive stage of labor. Basal levels rose to 43.1 +/- 16 microU/ml and 38.7 +/- 12.6 microU/ml, and peak levels to 77.4 +/- 19.1 microU/ml and 91.6 +/- 21 microU/ml in the jugular and utero-ovarian veins, respectively. Interpeak intervals had decreased to 17.2 +/- 3.3 min (P < 0.05). Oxytocin levels remained high after delivery of the calf until the placenta was expelled. The posterior pituitary was the source of circulating OT during most of gestation and labor, but the solo peaks observed during late gestation in the utero-ovarian vein were probably of luteal origin or possibly of caruncular origin, because near term, both tissues express OT mRNA. Fetal posterior pituitary is another possible source for these peaks. Our conclusions are that during bovine pregnancy, low amplitude spurts of OT are secreted intermittently; near term, both the frequency and peak amplitude of the spurts increase; and during labor, a dramatic increase in plasma OT precedes the expulsion of the calf. The main source of OT is the posterior pituitary, but near term, a utero-ovarian source secretes additional OT into the systemic circulation.     

Acute effects of unilateral ovariectomy in the baboonPapio cynocephalus

The purpose of this study was to determine if steroids secreted by one ovary affected the steroid secretion of the other ovary by direct transportation of the steroids via uterine blood vessels. Either two or three baboons were scheduled for ovariectomy on the day of ovulation and on alternate days from 1–15 days before the expected day of ovulation. Two days before the scheduled ovariectomy, utero-ovarian vein blood from both sides was collected by the use of a laparoscope. Measurement of estradiol (E₂) was carried out in these samples. The ovary with a higher concentration of E₂ was designated the dominant side. At the time of ovariectomy utero-ovarian vein and uterine vein blood from the two sides was again collected. After removal of the dominant side ovary another sample of utero-ovarian and uterine vein blood was collected. The interval between removal of one ovary and blood collection from the contralateral side ranged from 2–15 min. Steroids E₂, progesterone (P), testosterone (T), and androstenedione (A) were measured in the blood plasma. Of the 21 baboons 12, 12, 11, and 10 baboons showed an increase in E₂, P, T, and A values, respectively, on the contralateral side after unilateral ovariectomy. The time elapsed between pre-ovariectomy blood collection and post-ovariectomy blood collection as well as the day of the follicular phase, when these samples were collected had no effect on the increases and decreases on the contralateral side. Statistical analysis, however, showed that the change in utero-ovarian vein or uterine vein hormone levels on the contralateral side after removal of one ovary was not significant for any of the four hormones E₂, P, T, and A. Thus there is no evidence to demonstrate cross circulation of steroids from one ovary to the other via direct vascular channels. This research was supported by NIH grant HD15300 toA. A. Shaikh.     

Effects of prostaglandins on the cerebral circulation in the goat

The role of prostaglandins in producing cerebrovasodilation during hypercapnia was tested in goats. Cerebral blood flow (CBF) changes with increasing arterial PCO2 were measured before and after prostaglandin synthesis inhibition with indomethacin or ibuprofen. Both drugs produced significant decreases in CBF under control anesthetized conditions but had no significant effect on the cerebrovascular response to increased arterial PCO2. The effects of direct intracerebrovascular infusion of prostaglandin E₂ (PGE2), prostaglandin F2α (PGF2α) and prostacyclin were also measured. In the dose range tested (0.1–1 ug/min) PGF2α had no significant effect on cerebral blood flow (CBF). Both PGE2 and PGI2 produced an increase in CBF and the increase produced by PGI2 was significantly greater than that produced by PGE2. The effectiveness of each compound in producing cerebrovascular changes is consistent with the endogenous distribution of prostaglandins within the brain. These results suggest that prostaglandins, particularly PGI1, may be important in modulating cerebrovascular tone but have no role in increasing CBF during hypercapnia.     

Prostaglandin F concentrations in utero-ovarian vein plasma of prepuberal and mature gilts

Prostaglandin F (PGF) and progestins in utero-ovarian vein (UOV) plasma during the late luteal phase of the estrous cycle in unbred mature gilts and following induced ovulation in unbred prepuberal gilts were determined. Prepuberal gilts (120 to 130 days of age) were induced to ovulate with Pregnant Mare Serum Gonadotropin and Human Chorionic Gonadotropin (HCG). The day following HCG was designated as Day 0. Mature gilts which had displayed two or more estrous cycles of 18 to 22 days (onset of estrus = Day 0) were used. Polyvinyl catheters were inserted into the UOV of all gilts and blood was collected at 15 min intervals from 0800 to 1045 hr on Days 10 through 20 or Days 12 through 18. Plasma PGF concentrations in the mature gilts were elevated on Days 13, 14, 15, 16 and 17, whereas, plasma PGF concentrations in the prepuberal gilts were elevated only on Days 15, 16 and 17 resulting in a reproductive age (mature vs prepuberal) by day interaction (P<.01). In addition, the PGF concentrations on Days 13 through 17 were consistently greater in the mature gilts than in the prepuberal gilts as was the overall mean PGF concentration (1.95 vs .83 ng/ml). The average peak PGF concentration throughout the sampling period (4.6 vs 2.5 ng/ml; P<.01) and the average peak PGF concentration prior to luteal regression (3.8 vs 1.1 ng/ml; P<.05) were also greater in the mature than in the prepuberal gilts. Based on these results, we suggest that luteal regression in the bred prepuberal gilt following induced ovulation may not be due to an excessive production of the uterine luteolysin, but rather that the induced corpora lutea (CL) of the prepuberal gilt may be more sensitive to the uterine luteolysin than the spontaneously formed CL of the mature gilt.     

Concentrations of steroids in the utero-ovarian vein blood,serially collected from the two sides of individual baboons,during the follicullar phase

The purpose of this study was to determine and compare the follicular phase steroid hormone secretion into the utero-ovarian vein by the ovary with a dominant follicle and the contralateral ovary in the same baboon. Serial utero-ovarian vein blood from both sides was collected in 25 baboons by the use of a laparoscope on alternate days, starting on day 1 or 3 of the cycle and continuing through 2 to 3 days post-ovulation. Approximately 3–4 days before the day of expected ovulation, samples were collected at 8-hr intervals. Steroids estradiol (E₂) and progesterone (P) were measured in all utero-ovarian vein plasma by radioimmunoassay. In the peripheral plasma, E₂, P, LH, and FSH measurements were carried out. Concentrations of steroids were significantly higher on the side of the ovulating ovary by day 5 before ovulation. Individual plots however, indicated that some baboons may establish the dominant side as early as day 11 before ovulation. The preovulatory gonadotropins had a differential effect on the two ovaries. For example, E₂ values on the ovulatory side ovary declined after increases in LH/FSH, whereas on the contralateral side these values had increased. Both sides showed increases in the level of P with the increases in LH. The mean interval from E₂ peak to LH peak was 24 hrs and LH peak to ovulation was 24 hrs.