Concentrations of 15-keto-13, 14-dihydro-prostaglandin F2 alpha in the mare during spontaneous and oxytocin induced foaling

Changes in plasma 15-keto-13, 14-dihydro-prostaglandin F2 alpha were monitored at frequent intervals before, during and after spontaneous deliveries (three mares) and foalings induced by oxytocin (eight mares). No evidence of increased concentrations of the prostaglandin metabolite was observed in the final 10 days of gestation. In spontaneously delivering mares, there was a marked increase from 3 ng/ml at -125 mins to 18 ng/ml at -65 mins to the highest observed value of 182 ng/ml at 20 mins pre-partum. Following delivery, concentrations declined rapidly to around 0.2 ng/ml. Further release of prostaglandins was seen on Days 1 and 3 post partum. In oxytocin induced mares, maximal concentrations of about 100 ng/ml were observed to occur very close to the time of delivery. Large increases were observed as early as 2 mins following oxytocin injection. The significance of these findings is discussed in relation to parturient and post parturient events and changes in levels of the hormone relaxin during the same period.     

Arginine vasopressin stimulation of prostaglandin F2 alpha release in heifers during the estrous cycle

The effect of arginine vasopressin on the stimulation of prostaglandin F2 alpha (PGF2 alpha) release has been examined in vivo. Fifty-eight heifers received one intravenous injection of 10 IU arginine vasopressin on either Day 0 (n = 14), Day 6 (n = 12), Day 13 (n = 14) and Day 18 or 19 or 20 (Day 18-20, n = 18) after the onset of oestrus (Day 0) to determine the effect of arginine vasopressin at different times of the oestrous cycle. Frequent blood samples were taken before and after arginine vasopressin injection for the measurement of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) by radioimmunoassay (RIA). Blood samples for progesterone determinations were taken 2 hr before and 24 hr after arginine vasopressin to monitor luteal function. The data show that arginine vasopressin causes an increase (P less than 0.005) in PGFM concentrations only at Day 18-20 of the cycle in 67% of the experimental heifers.     

The effect of estrogen, progesterone and prostaglandin F2 alpha on uterine contractions in seasonally anovulatory mares

Uterine contractions were studied in two experiments utilizing ultrasonography and seasonally anovulatory mares. A one-minute ultrasound scan was done to produce longitudinal real-time images of the uterine body and an overall uterine contractile activity score (0 = no or minimal activity to 4 = maximal activity) was assigned to each scan. In experiment 1, a two-hour uterine activity trial (one score every 10 minutes) was done in mares given a single injection of prostaglandin F2 alpha (PGF2 alpha group; n = 4) and in control mares (n = 4). There was no difference between the two groups over the two-hour trial (mean activity score averaged over the two-hour trial: PGF2 alpha group, 0.2; control group, 0.1). In experiment 2, 16 mares were randomly assigned to one of four groups: 1) controls (corn oil vehicle), 2) 1 mg estradiol 17 beta on days 0 to 9 and 100 mg progesterone on days 10 to 20 (E2--greater than P4 group), 3) 100 mg progesterone on days 0 to 20 (P4 group), and 4) 100 mg progesterone on days 0 to 9 and 1 mg estradiol 17 beta + 100 mg progesterone on days 10 to 20 (P4--greater than E2 + P4 group). Uterine activity was assessed for each mare daily. The day by group interaction was significant. Scores for the E2--greater than P4 group were greater on days 4 to 11 (P less than .05) than for the other three groups. From day 14 to 21, scores did not differ among the three steroid-treated groups (except on day 15), but the scores averaged over each steroid-treated group were greater for each day (P less than .1 or .05) than for the controls (except on day 17).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of inhibition of prostaglandin F2 alpha synthesis on placental expulsion in the ewe.

Five ewes were injected with two doses of a nonsteroidal anti-inflammatory drug (NSAI), lysine acetyl salicylate, at birth of their first lamb and one hour later, and five others were injected once only, at birth of their first lamb. A control group of six animals was constituted. The times needed for fetal expulsion and placental release were recorded. The peripheral plasma PgF2 alpha (as PGFM) levels were measured prepartum during the seven last days of gestation, at parturition, then 1 h, 2 h and 12 h after lambing. The results were compared among and within treatment groups. They indicate that the physiological increase in peripheral PGFM levels starts two days before lambing and that the level peaks at lambing. The normal decrease after parturition is emphasized by NSAI injections as detected 1 h and 2 h posttreatment (p < 0.01). The NSAI drug is short-acting as revealed by the lower PGFM levels in twice-treated animals 2 h after birth compared to once treated animals and the similar low levels in all three groups 12 h after birth. The fetal membranes were expelled normally in all treated and nontreated animals, but the time needed for placental expulsion in ewes injected with two doses of NSAI was longer than in controls (p < 0.05). A negative correlation (p < 0.05) was found between plasma PGFM levels measured two hours after lambing and the time needed for fetal membrane expulsion. PgF2 alpha appears to have a role in placental release in the ewe.     

Changes in circulating prostaglandin E and F2 alpha levels, cloacal temperature, and leukocyte counts in turkeys inoculated with Pasteurella multocida

The inoculation of Pasteurella multocida (P-1059) intravenously into turkeys increased significantly the plasma prostaglandin (PG) F2 alpha levels to 157% of the control values and the plasma PGE levels to 171% of control values at 3 hr after treatment. At 12 hr, the cloacal temperature of the inoculated birds was significantly higher than that of the control. The leukocyte count of inoculated birds remained unchanged from that of the control. However, the differential leukocyte count shifted in favor of significant increases in heterophils and decreases in lymphocytes and monocytes at 6 and 12 hr after inoculation. This study provides evidence that increases in plasma levels of PGF2 alpha and PGE may be partly responsible for the clinicopathological manifestations of acute fowl cholera.     

Effects of prostaglandin F2 alpha on prolactin secretion in the fowl

The plasma concentration of prolactin in immature cockerels was increased between 10 and 40 min after the intravenous administration of prostaglandin (PG) F2 alpha (200 micrograms/kg body weight). Lower doses had no effect on plasma prolactin concentration. The addition of PGF2 alpha (10(-9) to 10(-6) M) to incubation media had no effect on the basal release of pituitary prolactin but reduced the release of prolactin from pituitary-hypothalamus co-incubations. The addition of noradrenaline (10(-7) M), serotonin (10(-7) M), acetylcholine (10(-6) M) or histamine (10(-6) M) to the co-incubation increased the hypothalamus-induced prolactin release, although these effects were not observed in the presence of 10(-7) M PGF2 alpha. The in vitro release of pituitary prolactin was increased by adding chicken hypothalamic extract in the presence or absence of PGF2 alpha. These results suggest a dual effect on PGF2 alpha of prolactin secretion in the fowl; its stimulation in vivo may result from a peripheral action.     

Effect of prostaglandin F2 alpha, phenylephrine and ergonovine on uterine contractions in the ewe

Two experiments were conducted to determine the effect of prostaglandin F2 alpha (PGF2 alpha), phenylephrine and ergonovine on uterine contractions. In the first experiment, ewes were bilaterally ovariectomized, and a strain gauge force transducer was sutured to the serosa of one uterine horn. Each ewe was treated sc with 2 micrograms of estradiol-17 beta daily to prevent regression of the uterus. Beginning at least 5 d after ovariectomy, four dose levels of PGF2 alpha, phenylephrine and methoxamine were given by im injection and ergonovine was given by im or iv injection. Phenylephrine, methoxamine and ergonovine are alpha-adrenoceptor agonists. Uterine activity was recorded by physiograph for 30 min before and 90 min after treatment. Tracing were analyzed for 20-min periods before treatment and 4 to 24 min and 50 to 70 min after treatment. In Exp. 2, transducers were attached to uteri of intact ewes at d 10 to 12 of an estrous cycle. During subsequent estrus, one or two dose levels of PGF2 alpha, phenylephrine and ergonovine were given by im injection and uterine activity recorded. In Exp. 1, PGF2 alpha and phenylephrine increased (P less than .05 or .01) the number of amplitude of contractions at both 4 to 24 and 50 to 70 min. Ergonovine given im increased the number of contractions. In intact estrous ewes, PGF2 alpha increased the number and amplitude of contractions at 4 to 24 min, phenylephrine increased the number and amplitude at both 4 to 24 and 50 to 70 min, and ergonovine increased the number slightly but significantly at 4 to 24 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of estrus by prostaglandin F2alpha administration in the vaginal vestibules of miniature pigs

Estrus induction is an important step in embryo production. It has been difficult to induce estrus in miniature pigs by intramascular (i.m.) injection of prostaglandin F2alpha (PGF2(2alpha)) in the early luteal stage of the estrous cycle. In the present study, we injected two different doses of PGF2(2alpha) i.m. and into the submucosa of the vaginal vestibule (i.ves.) of miniature pigs, and examined the effect of these treatments on estrus induction. Fifteen miniature pigs were divided into five experimental groups (control, saline injected i.m.; PGF2alpha treated, 1.0 or 1.5 mg of PGF2alpha injected twice i.m. or i.ves.), and the estrus length and concentrations of 17beta-estradiol (E2) and progesterone (P) in the blood were examined. Estrus length was significantly shortened by a large amount of PGF2alpha injected i.ves. In addition, the concentration of P in the blood significantly decreased after two injections of PGF2alpha (i.m. or i.ves.). These results suggest that in miniature pigs, administration of at least 3.0 mg of PGF2alpha is required for the induction of luteolysis and injection of PGF2alpha into the vaginal vestibule is a useful method of estrus induction.     

Influence of infusion of prostaglandin F2 alpha (PGF 2 alpha) and weaning on surface and histologic populations of ovarian follicles in early postpartum beef cows

Twenty-four beef cows were infused continuously for 11 d (d 2 to 13 after parturition) into the descending aorta with either prostaglandin F2 alpha-Tham salt (PGF2 alpha; 33.5 mg/d; n = 12) or with .9% NaCl (saline; n = 12) vehicle. Cows from each infusion treatment then were assigned to three slaughter groups (G). Cows in G1 and G2 were suckled until slaughter on d 15 and 35, respectively, whereas calves in G3 were weaned on d 31 and cows were slaughtered on d 35 after parturition. Nonatretic and atretic (greater than 4 pycnosis) antral follicles (greater than .15 mm) on ovaries ipsilateral to the previously gravid uterine horn were evaluated by histological techniques. Compared with saline infusion, PGF2 alpha increased mean diameters of the largest (F1) follicles on the ipsilateral (d 15 and 35; P less than .07) and contralateral (d 15; P less than .07) ovaries (surface evaluation) as well as mean diameters of the largest (F1, d 35; P less than .002), second- and third-largest (F2, F3 d 15 and 35; P less than .01) nonatretic follicles (histologic evaluation) in suckled cows. Compared with suckled cows slaughtered on d 35, weaning on d 31 increased the number of medium follicles (3 to 5 mm), diameters of the three largest nonatretic follicles, percentage of large nonatretic follicles (greater than 3.67 mm) and mitotic index of class 3 (.68 to 1.57 mm) follicles in saline-infused cows. In contrast, in PGF2 alpha-infused cows, weaning decreased (P less than .05 to P less than .001) all of these responses. Surface and histologic evaluations of follicular activity indicated that postpartum infusion of PGF2 alpha stimulated development of large follicles. In response to weaning, PGF2 alpha infusion favored development of those large follicles toward ovulation or atresia on nonovulated follicles.     

Intravaginal prostaglandin F2 alpha for the treatment of metritis and pyometra in the bitch

The purpose of this study was to determine whether intravaginal prostaglandin F2 alpha (PGF2 alpha) would be effective for the treatment of metritis or pyometra in the bitch. Seventeen bitches with metritis or pyometra were treated with PGF2 alpha. Prostaglandin F2 alpha (150 micrograms/kg body weight) was administered once or twice daily by infusing 0.3 ml per 10 kg body wt into the vaginal lumen. Bitches were also treated with amoxicillin (15 mg/kg body wt/48 h) and/or gentamicin (4 mg/kg body wt/day) administered as intramuscular (i.m.) injections. Fifteen bitches were treated successfully with intravaginally administered PGF2 alpha for 3 to 12 days and with intramuscularly administered antibiotics for 4 to 12 days. Success of treatment was judged by cessation of vaginal discharge, the absence of fluid in the uterus as determined by ultrasonography, and the overall health status of the animal. As two bitches with pyometra showed clinical deterioration in spite of medical treatment, ovariohysterectomy was performed after the first and the second treatment, respectively. No side effects (salivation, vomiting, diarrhoea, hyperpnoea, ataxia, urination, anxiety, pupillary dilatation followed by contraction) were observed after PGF2 alpha treatment. The disease did not recur during the subsequent oestrous cycles within 12 months after the initial treatment. The results demonstrate that intravaginal administration of PGF2 alpha was effective in 13 dogs (86.6%) with metritis or pyometra, and caused no side effects. Although the study was based on a relatively small number of cases, it is concluded that prostaglandin F2 alpha can be a useful means of treating bitches with metritis or pyometra. However, in severe cases of pyometra ovariohysterectomy is needed.     

Steroid concentrations in cows with corticotropin-induced cystic ovarian follicles and the effect of prostaglandin F2alpha and indomethacin given by intrauterine injection.

In 7 instances, cystic ovarian follicles resulted when adrenocorticotropin (ACTH) was administered daily during the follicular phase of the estrous cycle in cows. Two cows given daily injections of hydrocortisone (cortisol) during the follicular phase of the estrous cycle did not develop cystic ovaries. Plasma concentrations of estradiol in cows with induced cystic ovarian follicles were similar to the peak values observed at estrus and were between 6 and 12 pg/ml. Progesterone concentrations in plasma of cows with cystic ovaries were low, between 1 and 2 ng/ml. Ovulation occurred when 2 cows were given human chorionic gonadotropin (HCG) during the period of ovarian cyst development with ACTH administration. Several days of administration of ACTH was required to cause cyst development. Ovulation occurred at the expected time in 1 cow when injections began on day 19, that is, late in the follicular period. In another cow, when treatment was stopped on day 3, after the expected time of estrus a delayed ovulation occurred. In 2 cows with induced cystic ovarian follicles, cyst atresia occurred spontaneously about day 13 to 17 of the cycle. In these cows, new follicular growth and ovulation followed (although delayed in 1 cow). The time of atresia of cystic follicles was not influenced by the intrauterine injection of 10 ml of sterile saline solution on days 8, 9, and 10 in 1 cow. When 5 mg of prostaglandin F2alpha in 10 ml of sterile saline solution was given (uterine injection) in 2 cows on days 8, 9, and 10, cyst atresia occurred earlier than the time of spontaneous atresia. Intrauterine administration of 100 mg of indomethacin in 10 ml of sterile saline solution daily for 13 or 14 days to 2 cows, starting on day 12 or 13 of the cycle, resulted in persistence of the induced cystic ovarian follicles. After cessation of indomethacin treatment, atresia of cysts followed and new follicular growth and ovulation occurred.     

Use of prostaglandin F2 alpha for early pregnancy termination in the mismated bitch

Natural PGF administered at a dose of at least 250 micrograms/kg twice daily subcutaneously for at least 4 days starting no earlier than day 5 of cytologic diestrus induces luteolysis and pregnancy termination in the mated bitch. The resulting shortening of the luteal phase is associated with a shortening of the interestrous interval from 1 to 4 months. Bitches treated with PGF show emesis, diarrhea, and panting within 5 minutes and transient hypothermia which lasts 2 to 3 hours but generally have no further reaction. Bitches with cardiac or respiratory dysfunctions are not considered safe patients for early pregnancy termination with PGF because of the cardiovascular effects of this drug. Bitches treated with this regime early in diestrus resorb their conceptuses; those treated after days 35 to 40 show clinical abortion of viable fetuses.     

Relative oxytocic properties of fenprostalene compared with cloprostenol, prostaglandin F2 alpha, and oxytocin in the ovariectomized ewe

The oxytocic effect of a prostaglandin F2 alpha analogue, fenprostalene, was assessed in 4 ovariectomized ewes fitted with electrodes in both uterine horns and in the cervix. In the absence of estradiol priming, significant motility changes were not elicited by fenprostalene. Conversely, when ewes were primed with 17-beta-estradiol, fenprostalene markedly increased the electrical activity in the uterus and cervix. After a single subcutaneous fenprostalene administration (5 micrograms/kg), activity values remained about twice that of the control values during 8.52 +/- 3.31 hours. When the same dosage was administered IM, similar post-injection activity values were obtained, but only during 5.88 +/- 0.72 hours. Oxytocic effects of fenprostalene were far longer than those elicited by a single IM administration of 50 micrograms of prostaglandin F2 alpha (tham salt)/kg (0.91 +/- 0.32 hours) or by a single IM administration of 1 microgram of cloprostenol/kg (1.88 +/- 0.81 hours). Using the dose-effect relationship curve obtained from the same ewes by continuous IV infusions of oxytocin (OXT), the postinjection activity values reached after a single subcutaneous administration of fenprostalene were equivalent to those of an IV infusion of OXT at an average dose of 4.09 ImU of OXT/kg/hr for 6 to 13 hours, according to the values of the particular ewe concerned. These long-lasting oxytocic properties, in addition to its luteolytic capabilities, would make fenprostalene a suitable drug for promoting effective evacuation of the uterus when required in daily veterinary practice.     

Oxytocin modulates the pulsatile secretion of prostaglandin F2alpha in initiated luteolysis in cattle

Subluteolytic doses of prostaglandin F2alpha analogue (oestrophan) given i.m. and oxytocin (OT) antagonist (CAP) and noradrenaline (NA) infused into the abdominal aorta were used to test the importance of luteal OT in pulsatile secretion of prostaglandin F2alpha (PGF) during luteolysis in heifers (n = 17). In experiment 1, heifers were pre-infused for 30 minutes with saline on either day 17 of the oestrous cycle (group 1; n = 4) or on day 18 of the oestrous cycle (group 2; n = 3), and with CAP (8 mg per animal) on day 17 of the oestrous cycle (group 3; n = 4). Next, heifers were injected with oestrophan (30 microg per animal). Injection of oestrophan in Group 3 increased OT concentrations (P < 0.001) to values similar to those observed during spontaneous luteolysis (50 to 70 pg ml(-1)). PGFM concentrations in this group also increased (P < 0.001), but were lower (P < 0.05) than the values in groups 1 and 2, CAP given prior to oestrophan decreased both PGFM elevation (P < 0.06) and its area under the curve (P < 0.01), compared to the saline pretreated heifers. In experiment 2 NA (4 mg) was infused twice for 30 minutes at five hour intervals to release OT on day 17 of the oestrous cycle (n = 6). However, during hormone analysis it appeared that three of six heifers had elevated PGFM concentrations (group 1) and three others did not (group 2). NA caused the correlated increase of progesterone and OT secretion (r = 0.68; P < 0.05) in both groups but it only influenced PGF secretion in group 1 only (P < 0.05). We postulate that OT can amplify and modulate the course of induced luteolysis as a regulator of the amplitude of pulsatile PGF secretion. PGF analogue stimulates secretion of endogenous PGF from the uterus in cattle and this may be an important component of the luteolytic response to exogenous PGF.     

Prevention of pregnancy in the dog with a combination of prostaglandin F2 alpha and bromocriptine

Fifteen mated bitches were given prostaglandin F2 alpha (PGF2 alpha) [250 micrograms/kg body weight] and bromocriptine (10 micrograms/kg BW) twice daily from days 6 to 10 of diestrus. Progesterone concentrations declined during treatment. None of the bitches whelped. Daily treatment with PGF2 alpha and bromocriptine for 5 d appears to induce luteolysis and prevent early pregnancy.