Effects of prostaglandin F2alpha treatment on the behavior of pseudopregnant pigs in an extensive environment

In seminatural environments, prepartum sows leave the herd and construct a maternal nest (a dug out hollow lined with vegetation) prior to the birth of their piglets. The endocrine drives motivating this behavior are not understood, but may involve prostaglandin (PG) F2alpha. This study examined the effect of PGF2alpha treatment on the behavior of pseudopregnant gifts housed in a large enclosure. Pseudopregnancy was induced using 5 mg/ml estradiol valerate/day im from days 11 to 15 of the estrous cycle (first day of estrus = day 0). The gifts' behavior was recorded on a control day, during which no treatment was given, and a test day (= 45.9 +/- 0.42 days of pseudopregnancy) when gilts received either 15 mg PGF2alpha (dinoprost: Lutalyse, Upjohn, Crawley, UK, n = 11) or 0.9% saline (n = 10) im at 11.00 h. PGF2alpha-treated gilts traveled further and were more frequently >10 m from the nearest pig than saline-treated animals. In the hour following injection, PGF2alpha-treated animals also showed increased frequencies of rooting and pawing the ground and stood for longer than saline-treated animals. However, gathering and carrying nest materials were not increased. These results suggest that PGF2alpha, given as a single dose to extensively housed gilts, initiated many, but not all, of the behaviors characteristic of prepartum nest building. The dose and duration of PGF2alpha treatment may have limited the observed behaviors. In addition, environmental feedback is likely to affect the degree to which some nest building behaviors are expressed.     

Acute effects of prostaglandin F(2alpha) on systemic oxytocin and progesterone concentrations during the mid- or late-luteal phase in mares

The acute effects of prostaglandin F(2alpha) (PGF) on circulating oxytocin and progesterone concentrations were characterized in mares during the mid- or late-luteal phase. Pony mares were randomly assigned to the following experimental groups based on treatment with PGF (2.5mg) or saline on Day 8 or Day 13 (Day 0=ovulation): PGF-8, PGF-13, saline-8, or saline-13 (n=7/group). Mares were fitted with indwelling, jugular vein catheters and two blood samples (-5 and 0 min) were collected prior to treatment. Treatments were administered into the jugular vein (0 min) and blood collection continued thereafter at 1 min intervals until 5 min and then at 5 min intervals until 60 min. Based on the combined data of -5 and 0 min samples, mares on Day 8 had greater (P<0.05) oxytocin concentrations than mares on Day 13. On Day 8, PGF treatment resulted in a biphasic pattern of oxytocin release. Oxytocin concentrations increased (P<0.05) 1 min after PGF treatment, decreased (P<0.05) from 1 to 10 min, and increased (P<0.05) from 10 to 30 min. Oxytocin concentrations were greater (P<0.05) from 1 to 3 min in PGF-treated than saline-treated mares and at most sample times from 15 to 60 min. On Day 13, oxytocin concentrations were greater (P<0.05) in PGF-treated than in saline-treated mares for most sample times. Mares treated with PGF on Day 8 had greater (P<0.05) oxytocin concentrations at 25, 30, and 40 min than mares on Day 13. Progesterone concentrations on Day 8 also increased by 1 min after PGF, decreased toward basal concentrations by 2-3 min, and then increased to a maximum 10 min after treatment. Subsequently, circulating progesterone decreased (P<0.05) below pretreatment concentrations by 40-50 min after PGF. In conclusion, treatment with PGF resulted in an immediate and biphasic increase in progesterone concentrations prior to the expected decrease. Treatment of mares with PGF on Day 8 resulted in an overall greater increase in systemic oxytocin concentrations compared to treatment on Day 13, and the increase on Day 8 was biphasic.     

Effects of prostaglandin F2alpha treatment of pseudopregnant pigs on nest building and interactions with newborn piglets

Previous studies showed that prostaglandin (PG)F2alpha treatment stimulated nest building behaviors in prepartum and pseudopregnant pigs. This experiment studied behaviors of PGF2alpha-treated pseudopregnant nulliparous pigs (gilts) exposed to newborn piglets. Penned pseudopregnant gilts (days 46-53) were injected with either 10 mg PGF2alpha (n = 8) or saline (n = 8) im, and behavior was recorded for 2 h (period A). Between 2 and 6 h (period B), gilts were given two male piglets (< 12 h old) and a novelty object (house brick) and recordings continued. During period A, PGF2alpha animals showed greater frequencies of standing, pawing, rooting, lifting, and carrying straw (indices of nest building) and scratching than saline treated animals. During period B, one PGF2alpha- and two saline-treated gilts attacked piglets, which were removed from the pen and the gilts excluded from further analysis. There were no treatment differences in period B in gilt posture, nest building behavior, or interactions with piglets or novelty object, except for a reduced frequency to trap piglets beneath their bodies and an increased frequency to attempt to escape from the pen in PGF2alpha-treated animals. Piglet position relative to the gilts' head and udder was unaffected by treatment. Gilts in both groups approached and nosed piglets more within the first 30 min of period B than subsequently. PGF2alpha-induced nest building had only a weak impact upon subsequent interactions between gilts and piglets, suggesting that mechanisms controlling porcine nest building and maternal behavior in this model were not directly linked.     

Daily changes in peripheral plasma progesterone concentrations in pregnant and pseudopregnant rabbits

Peripheral levels of plasma progesterone were found to be similar in pregnant New Zealand White and Dutch-belted rabbits. In early gestation progesterone concentrations rose rapidly, remained relatively constant and declined slowly during the latter third of pregnancy. Among pseudopregnant rabbits progesterone levels rose rapidly until day 11 and declined rapidly thereafter until day 19 at which time baseline values were obtained.     

In vivo levels of prostaglandin F2 alpha, E2 and prostacyclin in the corpus luteum of pregnant and pseudopregnant rats

Prostaglandin F2 alpha (PGF2 alpha) is a well-known luteolytic factor in the rat corpus luteum. To investigate a possible luteal origin of PGF2 alpha, measurements of this prostaglandin were performed in different luteal tissues in vivo. Prostaglandin E2 (PGE2) and the stable metabolite of prostacyclin, 6-keto-PGF1 alpha, were assayed simultaneously. Corpora lutea of different ages from 57 pregnant and pseudopregnant rats (mated with sterile males) were rapidly excised, dissected in 0 degree C indomethacin solution, homogenized, and extracted for prostaglandins with solid-phase extraction cartridges. Prostaglandins were determined by radioimmunoassay. Plasma levels of progesterone and 20 alpha-dihydroprogesterone were also monitored. In the adult pseudopregnant rat model, luteolysis occurs at Day 13 +/- 1, and maximal levels of all three prostaglandins were detected on Day 13 of pseudopregnancy: 0.40 +/- 0.02, 2.6 +/- 0.29, and 1.76 +/- 0.24 pmol/mg protein (mean +/- SEM, n=7) for PGF2 alpha, PGE2, and 6-keto-PGF1 alpha respectively. In pregnant rats, on the corresponding day, levels were considerably lower: 0.15 +/- 0.02, 0.90 +/- 0.13, and 0.50 +/- 0.06 pmol/mg protein (mean +/- SEM, n=9, p less than 0.0001), respectively. Luteal levels in pregnant rats showed a continuous decline on Days 13 and 19 for all prostaglandins measured, whereas in pseudopregnant rats an increment of PGF2 alpha was noted between Days 7 and 13 and remained high on Day 19. PGE2 closely followed levels of PGF2 alpha, but at a 5- to 10-fold higher level. The coefficient of correlation between PGF2 alpha and PGE2 in the luteal compartment of both models was 0.87 (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the lytic response of prostaglandin F2 alpha in Zebu cattle based on serum progesterone

To evaluate by means of blood progesterone levels and estrous expression the effect of the injection of 25 mg of PGF2alpha in Zebu cows, 17 Indobrazil cows with a palpable corpus luteum (CL) were injected with PGF2alpha and blood samples taken every 6 h in Experiment I. In Experiment II, 15 cows from the previous experiment at the same stage of diestrus were injected with PGF2alpha and bled every 4 h for 5 d. Progesterone levels had declined by 50% 6 h after injection in all cows and dropped to below 1 ng/ml by 30 h. Estrus was observed in 47% of the animals in Experiment I and 60% in Experiment II. Ovulation was detected accurately in 29% of the animals at 33.6 +/- 11.6 h after the onset of estrus. The correlation between finding a CL by rectal palpation and levels of progesterone higher than 1 ng/ml of blood was 86 and 93% in Experiments I and II, respectively. These studies indicate that the injection of 25 mg of PGF2alpha is sufficient to produce luteolysis in Zebu cattle, although estrous expression is poor.     

Acute stimulatory effects of an LH-RH agonist on the ovary in pseudopregnant rats

Pseudopregnant rats were anaesthetized on day 5 of pseudopregnancy with pentobarbital and hypophysectomy or sham operation was performed. Polyethylene cannulas were inserted into one of the femoral arteries and utero-ovarian veins. Five-minute blood samples were collected from the ovary for 40 minutes. Following the first five minute blood fraction LH-RH, an agonistic analogue (D-Phe6, des Gly-NH10(2)-LH-RH-ethylamide) or an antagonistic analogue (Formyl-D-Tryp1,3, D-pCl-Ph2, D-Phe6LH-RH) were superfused into the ovarian bursa for 5 minutes in a volume of 50 microliters. Blood pressure, ovarian venous outflow and haematocrit were continuously measured. From the blood samples progesterone and oestradiol-17 beta were determined by RIA and the secretion rate was calculated. It was found, that LH-RH and its antagonistic analogue has no effect on the blood flow, progesterone (P) and oestradiol-17 beta (E2) secretion of ovary. However, an agonistic analogue of LH-RH induced a rapid elevation of blood flow, diminished vascular resistance in the ovary, and in a dose of 50 ng increased the secretion rate of E2. In sham operated animals the effects of agonistic analogue was similar to the effects of 1.0 IU of hCG.     

Changes in corpus luteum content of prostaglandin F2 alpha and E in the adult pseudopregnant rat

Conflicting reports exist regarding the source of luteolytic PGF2 alpha in the rat ovary. To assess the quantities of different PGs, measurements of PGF2 alpha, PGE and PGB were performed by radioimmunoassay in the adult pseudopregnant rat ovary throughout the luteal lifespan. Ovaries of 84 rats were separated by dissection into two compartments, corpora lutea of pseudopregnancy and remainder of ovary. Tissue samples were homogenized and prostaglandins extracted and determined by radioimmunoassay. During the mid-luteal and late-luteal phases, levels of PGs were significantly higher in the corpora lutea of pseudopregnancy than in the remainder of ovary. An increase of PGF2 alpha-content in the corpus luteum was registered with peak-levels of 53.9 +/- 8.5 (mean +/- SEM, N = 18) ng/g tissue wet weight at day 13 of pseudopregnancy. PGE-levels reached peak-values at day 11 of pseudopregnancy (271.6 +/- 28.4 ng/g w w, mean +/- SEM, N = 12). PGB-levels were below detection limits in all compartments for all ages studied. The present study demonstrates increased availability of PGF2 alpha in the corpus luteum during the luteolytic period, and points toward either increased luteal synthesis or luteal binding of PGF2 alpha during the luteolytic period.     

Plasma prostaglandin F2alpha and 15-keto-F2alpha concentrations during splanchnic artery occlusion shock.

Arterial plasma concentrations of PGF2alpha and 15-keto-PGF2alpha were determined in sham shock and splanchnic artery occlusion shock dogs. Arterial PGF2alpha concentrations (expressed as percentage of control) increased significantly in the SAO group when compared to the sham group during postrelease sampling periods. Similarly, 15-keto-PGF2alpha, a major metabolite of PGF2alpha also increased significantly in arterial blood in SAO shock. Comparison of 15-keto-PGF2alpha and PGF2alpha at each sampling period suggest that the efficiency of 15-hydroxyprostaglandin dehydrogenase is not impaired during SAO shock in the dog. However, the ability of the kidney and other organs to remove 15-keto-PGF2alpha from the circulation during SAO shock does appear to be significantly reduced. Although the changes in circulating concentrations of PGF2alpha are significant, the role of the increased prostaglandin is not clearly understood. We found no basis for any toxic effect of the PGF2alpha nor of any beneficial action. Others, however, have found exogenous PGF2alpha to improve survival in circulatory shock.     

Effect of prostaglandin F2 alpha (PGF2 alpha) on sources of progesterone and pregnancy in intact, ovariectomized and hysterectomized 90-100 day pregnant ewes.

A single dose of 8 or 16 mg of PGF2 alpha per 58 kg body weight was injected intramuscular into intact, ovariectomized or hysterectomized 90-100 day pregnant sheep in three separate experiments. Both doses of PGF2 alpha decreased the weights of the corpora lutea (P less than or equal to 0.05) and the concentration of progesterone in ovarian venous plasma at 72 hr (P less than or equal to 0.05) compared to the 0 hr sample within treatment groups and to control ewes at 72 hr in intact and hysterectomized pregnant ewes. In hysterectomized pregnant ewes, progesterone in jugular plasma declined (P less than or equal to 0.05) from 0 to 72 hr but never fell below 4 mg/ml and this decrease in progesterone after 8 or 16 mg PGF2 alpha was greater than in control hysterectomized ewes (P less than or equal to 0.05). There was a significant decrease in progesterone over time in jugular or uterine venous plasma in the presence of absence of the ovaries in 90-100 day pregnant ewes (P less than or equal to 0.05) but the profiles of progesterone were not different between vehicle and PGF2 alpha-treated ewes (P greater than or equal to 0.05). Uterine venous progesterone never declined below 30 ng/ml in the presence or absence of the ovaries and there was a significant quadratic increase (P less than or equal to 0.05) in uterine venous progesterone toward the end of the 72 hr sampling period indicating an increase in steroidogenic activity of the placenta. PGF2 alpha did not affect the number of abortions in intact or ovariectomized pregnant ewes (P greater than 0.05). Thus, the corpus luteum of sheep at 90-100 days of pregnancy is functional and responsive to PGF2 alpha, placentomes are functional but do not appear to be responsive to the doses of PGF2 alpha tested and PGF2 alpha was not an abortifacient over the 72 hr treatment period.     

Central cardiovascular and thermal effects of prostaglandin F2 alpha in rats.

Administration of PGF2 ALPHA (0.2--6.4 micrograms) into the lateral cerebral ventricle (i.c.v.) induced dose-dependent increases in blood pressure, heart rate and body temperature in urethane-anaesthetised rats, but had no effect on these parameters when the same dose range was administered intravenously. Peripheral pretreatment with sodium meclofenamate (50 mg/kg s.c.) shifted all the dose-response curves for PGF2 alpha (i.c.v.) to the left, but indomethacin (50 mg/kg s.c.) did not significantly affect those changes. Central pretreatment with sodium meclofenamate or indomethacin (1.25 mg per rat i.c.v.) failed to modify significantly the effects of centrally administered PGF2 alpha. The results support previous suggestions that PGF2 alpha may participate in the central control of the cardiovascular and thermoregulatory systems, and also suggest that there may be differences in the sites and/or modes of action between sodium meclofenamate and indomethacin.     

Peripheral plasma levels of progesterone in pregnant goats and in pregnant goats treated with prostaglandin F2a

Prostaglandin or prostaglandin analogues have been shown to be luteolytic in the pregnant goat. In this study the temporal changes in the plasma concentrations of progesterone during pregnancy and after administration of PGF2a to pregnant goats are described. PGF2a administration to pregnant goats at 30 and 65 days after breeding induced abortion within 34 to 75 hours. These abortions were accompanied by estrus and profuse muco-hemorrhagic discharges. When PGF2a was administered to pregnant goats 140 or 142 days after breeding, premature parturition occurred within 42 to 76 hours. Live kids were delivered in all cases. The plasma levels of progesterone in all pregnant goats showed dramatic decreases within 24 hours after the prostaglandin injections and continued to decrease gradually until abortions or premature parturition. Thereafter, the progesterone levels remained low for several days.