Interleukin 1 and prostaglandin production by cells of the mononuclear phagocyte system isolated from mycobacterial granulomas

A study has been made of the activity of interleukin 1 (IL-1) and prostaglandins (PGs) in the culture supernatants from unstimulated and lipopolysaccharide (LPS)-stimulated mycobacteria-induced granuloma cells. Both epithelioid cells from bacillus Calmette-Guerin (BCG)-induced granulomas and macrophages from Mycobacterium leprae-induced granulomas, separated on a fluorescence-activated cell sorter using monoclonal antibody specific to guinea pig macrophages, spontaneously secreted low levels of IL-1 (assayed by thymocyte comitogenic and fibroblast mitogenic activities) into culture supernatants. However, culture supernatants from LPS-stimulated epithelioid cells showed significantly higher IL-1 activity than those from unstimulated cells. In contrast, LPS stimulation of M. leprae granuloma macrophages failed to enhance IL-1 production. Nevertheless, IL-1 activity in the culture supernatants from stimulated mycobacterial granuloma cells of both types was much lower than that from LPS-stimulated peritoneal exudate macrophage culture supernatants. There was no detectable amount of prostaglandin E2 (PGE2) in the culture supernatants from both unstimulated and LPS-stimulated BCG- and M. leprae-induced granuloma cells in comparison to much higher levels of PGE2 produced by unstimulated (0.28-6.2 ng/ml) or LPS-stimulated (greater than 15 ng/ml) peritoneal exudate macrophages. However, BCG granuloma cells either secreted prostaglandin F2 alpha (PGF2 alpha) spontaneously or produced comparable levels of PGF2 alpha to those from peritoneal exudate macrophages on stimulation, while M. leprae granuloma macrophages produced much lower levels of PGF2 alpha.     

Uterine vein prostaglandin levels in late pregnant dogs.

We studied the uterine venous plasma concentrations of prostaglandins E2, F2 alpha, 15 keto 13,14 dihydro E2 and 15 keto 13,14 dihydro F2 alpha in late pregnant dogs in order to evaluate the rates of production and metabolism of prostaglandin E2 and F2 alpha in pregnancy in vivo. We used a very specific and sensitive gas chromatography-mass spectrometry assay to measure these prostaglandins. The uterine venous concentrations of prostaglandin E2 and 15 keto 13,14 dihydro E2 were 1.35 +/- .27 ng/ml and 1.89 +/- .37 ng/ml, respectively; however, we could not find any prostaglandin F2 alpha and very little of its plasma metabolite in uterine venous plasma. Since uterine microsomes can generate prostaglandin F2 alpha and E2 from endoperoxides, prostaglandin F2 alpha production in vivo must be regulated through an enzymatic step after endoperoxide formation. Prostaglandin E2 is produced by pregnant canine uterus in quantities high enough to have a biological effect in late pregnancy; however, prostaglandin F2 alpha does not appear to play a role at this stage of pregnancy.     

Concentrations of prostaglandin E2 and F2 alpha in the cardiovascular system of infants with persisting patent ductus arteriosus

The distribution of prostaglandin E2 and F2 alpha was examined in the peripheral veins and in several positions of the cardiovascular system before and after the blood had passed through the lungs in 37 infants. Prostaglandin E2 varied from 0.25 +/- 0.09 ng/ml to 0.44 +/- 0.09 ng/ml when measured in the pulmonary artery, the ductus arteriosus, the right atrium, the right ventricle, the left atrium, the left ventricle, the inferior vena cava and the descending aorta. Prostaglandin F2 alpha was much higher in these positions of the cardiovascular system. The range was 0.99 +/- 0.36 ng/ml to greater than 2.0 ng/ml. The vascular tissues produced virtually identical high amounts of prostaglandin E2 and F2 alpha, but there were no significant differences in prostaglandin E2 and F2 alpha, concentrations, in venous blood as well as in systemic arterial blood. The results suggest that prostaglandin E2 is not responsible for the persisting patency of the ductus arteriosus in infants. There is no explanation for the increased prostaglandin F2 alpha concentrations in these patients.     

Effect of prostaglandin I2 and related compounds on vascular permeability response in granuloma tissues

The effects of prostaglandin I2, 6-ketoprostaglandin F1alpha, prostaglandin E1 and thromboxane B2 on the vascular permeability response in rat carrageenin granuloma were studied with the aid of 131I- and 125I-human serum albumin as indicators for the measurement of local vascular permeability. A single injection of 5 microgram of prostaglandin I2 methyl ester or I2 sodium salt into the locus of the granulomatous inflammation elevated local vascular permeability 2.0-2.5 times over the control within 30 min. The potency was equal to that of the positive control prostaglandin E1 which has been known to be the most potent mediator in this index among several candidate prostaglandins for chemical mediator of inflammation. The other prostaglandin and thromboxane B2 tested were essentially inactive.     

Synchronization of estrus in yearling beef heifers with the melengestrol acetate/prostaglandin F(2alpha) system: efficiency of timed insemination 72 hours after prostaglandin treatment

Two experiments were conducted to determine the conception rates of heifers time-inseminated following melengestrol acetate/prostaglandin F(2alpha) (MGA/PG) estrous synchronization treatment. In Experiment 1, timed insemination of heifers at 72 h after the PG injection, without regard for behavioral estrus, tended to improve (P < 0.15) the percentage of heifers pregnant to artificial insemination (AI) compared with that of synchronized heifers bred 12 h after they were first detected in estrus. In the timed-insemination treatment, heifers exhibiting behavioral estrus 48 to 72 h after PG tended to have an increased (P < 0.15) conception rate to AI compared with heifers exhibiting estrus within 48 h of PG administration. In Experiment 2, the number of heifers conceiving to AI following the MGA/PG estrous synchronization regimen was increased by mass insemination of all heifers not exhibiting estrus by 72 h after PG. The pregnancy rate to AI was higher in heifers with serum progesterone (P(4)) concentrations higher than 1 ng/ml compared with that of heifers with concentrations lower than 1 ng/ml. Of heifers with serum P(4) greater than 1 ng/ml, the pregnancy rate to AI tended to be higher when concentrations exceeded 2 ng/ml than when concentrations were 1 to 2 ng/ml. In cyclic heifers, timed insemination can increase the percentage of heifers pregnant after being synchronized with MGA/PG.     

Luteolytic activity of a synthetic prostaglandin and PGF2alpha in heifers.

Two experiments involving 44 cycling heifers were conducted to evaluate the luteolytic activity of a synthetic prostaglandin, AY 24366, and PGF2alpha. Activity was assessed by the decline in progesterone level of peripheral blood and occurrence of estrus. Progesterone concentrations of jugular blood plasma were quantified by radioimmunoassay. In the first experiment, 36 heifers were treated during diestrus with AY 24366 (A-10mg intrauterine, B-30mg intramuscular and C-60mg im) or with PGF2alpha (D-5mg iu, E-15mg im and F-30mg im). Mean progesterone 0, 24 and 48 hours after treatment were A-6.33, 5.55 and 5.06; B-6.35, 2.79 and 3.92; C-5.23, 2.69 and 3.91; D-5.19, 1.50 and 1.51; E-4.69, 0.85 and 0.61; F-6.66, 0.80 and 0.48 ng/ml. Standing estrus was observed in 1, 1, 1, 4, 5 and 6 females in groups A, B, C, D, E and F respectively within 72 hours of treatment. PGF2alpha resulted in significantly (P less than 0.01) lower progesterone at 24 and 48 hours than AY 24366. However, in administration of the latter did significantly (P less than 0.05) lower progesterone at 24 hours. In the second trial six heifers were treated with either 120 or 180mg of AY 24366 im on day 12 of the cycle. Mean progesterone declined from 3.84 to 2.12 ng/ml (P less than 0.01) by 6 hours and to 1.59 ng/ml by 12 hours. Thereafter the decline was gradual and reached a level of 0.65 ng/ml at 72 hours. All six heifers showed standing estrus at 78 +/-2 hours and were inseminated. Two in each group conceived. Doses of 15mg PGF2alpha and 120mg AY 24366 were effective in causing luteal regression, however, the latter caused respiratory discomfort for 5 to 10 minutes post treatment.     

Plasma concentration of progesterone during normal estrous cycles and following prostaglandin F(2alpha) treatment of Bos indicus and tropic-adapted Bos taurus heifers

The introduction of the use of prostaglandin F(2alpha) (PGF(2alpha)) to synchronize estrus in cattle adapted to the tropics suggests a need to investigate the endocrine response to this treatment. Progesterone (P) concentrations in blood plasma of Bos indicus and tropic-adapted Bos taurus heifers during normal estrous cycles and following estrus synchronization were compared. After PGF(2alpha) administration, the heifers were divided into two groups on the basis of response to treatment. Mean P levels in heifers showing estrus after the first injection ranged from 1.0-3.0 ng/ml, decreasing to 0.2-0.4 ng/ml 24 to 48 hr after treatment. The second group exhibited estrus only after the second PGF(2alpha) injection and had low P (0.2-0.9 ng/ml) in plasma before the first injection. Mean peak P levels in both groups 8 to 12 d after the first injection in the periestrous period were not different from values in the same heifers at similar periods of the preceding control estrous cycle. Neither the tropical location nor breed affected the luteolytic effect of PGF(2alpha).     

Influence of cortisol on prostaglandin synthesis by fetal membranes, placenta, and uterus of pregnant rabbits

Two experiments were designed to assess the effects of cortisol on prostaglandin formation in amniotic fluid and the prostaglandin-forming cyclooxygenase in 4 gestational tissues of rabbits. Cortisol treatment (12 mg/kg body wt/h) was initiated on Day 21 of pregnancy and continued for a 24-h period. Each experiment included 5 treated and 5 vehicle-injected controls, killed at 48 (Experiment 1) or 62 h (Experiment 2) after initial injection. In both experiments, amniotic fluid was collected; cortisol, prostaglandin F (PGF), and prostaglandin E2 (PGE2) were quantified by radioimmunoassay. Microsomes prepared from amnion, yolk sac splanchnopleure, uterus, and placenta were analyzed for prostaglandin-forming cyclooxygenase activity. In Experiment 2, blood drawn at 12-h intervals was quantified for PGF, PGE2, and progesterone. In cortisol-treated rabbits, plasma progesterone decreased (p less than 0.01) from 7.2 +/- 0.8 ng/ml on Day 21 (pre-treatment) to 1.6 +/- 0.2 ng/ml on Day 23, 48 h after the initiation of cortisol treatment. By 62 h, PGF, PGE2, and cortisol concentrations were all significantly higher (p less than 0.05) in the amniotic fluid of treated animals. However, prostaglandin-forming cyclooxygenase activity had not increased in most fetal or maternal tissues at either 48 or 62 h. Therefore, even though increased prostaglandin production may be responsible for the cortisol-induced abortion, increased cyclooxygenase activity in the fetal membranes, placenta, or uterus probably is not the primary stimulus for the increased prostaglandin synthesis.     

Doses of prostaglandin F(2)alpha effective for induction of estrus in goats

A total of 11 cycling does weighing between 24 and 50 kg were injected with varying dosages of prostaglandin F(2)alpha (PGF(2)alpha) between 7 and 10 days into each estrous cycle. Five injections each of 1.25, 2.5, 5.0, or 7.5 mg PGF(2)alpha were alternated with five injections of 1.0 ml saline. Saline treated does served as controls. All does were teased twice daily with a buck and observed for signs of estrus for 5 days post-injection. Daily systemic concentrations of progesterone (P(4)) were determined by radioimmunoassay. The mean (+/- S.E.) hours from injection to estrus was 47 +/- 3.3, 42 +/- 4.3, 44 +/- 8.5, and 43 +/- 5.5 for does receiving 1.25, 2.5, 5.0, and 7.5 mg PGF(2)alpha, respectively. None of the does receiving saline exhibited estrus in the 5-day post-injection observation period. Mean (+/- S.E.) concentrations of systemic P(4) in all does on the day of injection was 4.22 +/- 0.45 ng/ml. Concentrations 24 hours post-injection were 0.21 +/- 0.02, 0.15 +/- 0.05, 0.17 +/- 0.04, 0.16 +/- 0.04, and 4.5 +/- 1.36 ng/ml for does receiving 1.25, 2.5, 5.0, and 7.5 mg PGF(2)alpha, and 1.0 ml saline, respectively. The results suggested that 1.25 mg PGF(2)alpha was effective for induction of estrus in the cycling goat.     

Effect of prostaglandin F(2alpha)- thamsalt and Estrumate (ICI 80996) on plasma progesterone levels in Indian water buffaloes (Bubalus bubalis )

Thirty six buffalo showing normal reproductive cyclas were given a single intramuscular injection of prostaglandin F(2alpha)- thamsalt (PGF(2alpha)) and Estrumate on day 9 or 15 of the estrous cycle in order to induce estrus. In PGF(2alpha) treated animals, plasma progesterone dropped from 2.99+/-0.29 to 0.10 +/- 0.02 ng/ml and from 5.53 +/- 0.53 to 0.09 +/- 0.03 ng/ml (mean +/- SEM) within 72 hours of treatment, on day 9 and 15, respectively. Similarly, the treatment with Estrumate on day 9 or 15 of the cycle reduced the level of proges--terone from 3.02 +/- 0.03 to 0.14 +/- 0.03 ng/ml and from 4.26 +/- 0.47 to 0.21 +/- 0.03 ng/ml, respectively, 72 hours aPter each treatment. It was inferred that both drugs induce estrus in buffalo without any observed residual effect.     

Sequential appearance of IL-1 and IL-6 activities in rat carrageenin-induced pleurisy.

IL-1 and IL-6 activities were measured in the pleural exudate of rats during carrageenin-induced pleurisy to examine the relationship of the local production of cytokines to the inflammatory reaction. Time courses of appearance of the cytokines and inflammatory parameters in the exudate were compared. IL-1 activity and exudate volume started to increase at 1 h after the carrageenin injection, and then slightly later IL-6 activity and leukocyte number began to increase. IL-1 showed peak activity of approximately 700 U at 3 h and IL-6, of 6000 U at 5 h in the exudate, whereas exudate volume and number of polymorphonuclear leukocytes continued to increase thereafter. Furthermore, IL-6 level in the plasma of the carrageenin-injected rats showed a peak at 4 h (30 U/ml), and when rhIL-1 alpha (100,000 U) was intrapleurally injected, the more rapid increase in plasma IL-6 level was demonstrated at 1 h (30 U/ml). This latter rise was neutralized with simultaneous injection of anti-rhIL-1 alpha antibody. These facts indicate the possibility that IL-1 produced in the exudate or injected could rapidly propagate a signal to induce IL-6 production in the circulation. It took several hours to transmit an inflammatory signal that stimulated the liver to synthesize the acute-phase protein, T-kininogen. The time lag from the peak induction of IL-1 to the T-kininogen-increase in the pleurisy corresponded well to the interval for T-kininogen-increase by exogenous rhIL-1 alpha injection. These results strongly suggest that the initial inflammatory stimulus induces sequentially IL-1, IL-6, and T-kininogen production in this carrageenin inflammation.     

Role of prostaglandin H synthase-2 in prostaglandin E2 formation in rat carrageenin-induced pleurisy

Rat carrageenin-induced pleurisy was used to clarify the role of prostaglandin H synthase (PGHS)-2 in acute inflammation. Intrapleural injection of 0.2 ml of 2% λ-carrageenin induced accumulation of exudate and infiltration of leukocytes into the pleural cavity. When PGHS-1 and -2 proteins in the pleural exudate cells were analyzed by Western blot analysis, PGHS-2 was detectable from 1 hr after carrageenin injection. Its level rose sharply, remained high from 3 to 7 hr after injection, and then fell to near the detection limit. PGHS-1 was also detected, but kept almost the same level throughout the course of the pleurisy. Levels of prostaglandin (PG) E₂ and thromboxane (TX) B₂ in the exudate increased from hour 3 to hour 7, and then declined. Thus, the changes of the level of PGE₂ were closely paralleled those of PGHS-2.The selective PGHS-2 inhibitors NS-398, nimesulide and SC-58125 suppressed the inflammatory reaction and caused a marked decrease in the level of PGE₂ but not in those of TXB₂ and 6-keto-PGF_1α. These results suggest that the PGHS-2 expressed in the pleural exudate cells may be involved in PGE₂ formation at the site of inflammation.     

Autocrine/paracrine regulation of apoptosis in epithelial cells by prostaglandin E2

This study was designed to investigate the effect of IL-1alpha-induced up-regulation of cyclooxygenase-2 (COX-2) on prostaglandin E(2) (PGE(2)) secretion and the subsequent phenotypic effects of PGE(2) on epithelial cells. The effect of IL-1alpha on COX-2 expression was investigated in the T24 bladder epithelial cell line following treatment with 0, 0.05, 0.5, 1 or 10 ng/ml IL-1alpha for 1, 2, 4 or 6 h. Quantitative PCR confirmed up-regulation of expression of COX-2 with maximal expression observed following treatment with 0.5 ng/ml IL-1alpha for 1 h. Co-treatment of the cells with 0.5 ng/ml IL-1alpha in the presence or absence of 100 ng/ml IL-1 receptor antagonist (RA) abolished the up-regulation in COX-2 expression confirming that the effect of IL-1alpha is mediated via its membrane-bound receptors. Treatment with 0.5 ng/ml IL-1alpha resulted in a time-dependent increase in PGE(2) secretion with maximal secretion detected at 24 and 48 h after stimulation with IL-1alpha. Co-treatment of the cells with IL-1alpha and IL-1RA or the COX-2 enzyme inhibitor NS398 abolished the IL-1alpha mediated secretion of PGE(2). Treatment of T24 cells with 100 nM PGE(2) resulted in a significant elevation in cAMP generation confirming the expression of functional PGE(2) receptors. Finally, the effect of exogenous treatment with PGE(2) on apoptosis of T24 cells was assessed using cell death detection ELISA. T24 cells were treated with camptothecin to induce apoptosis in the presence or absence of 50 or 100 nM PGE(2) or 10 microM forskolin. Treatment of T24 cells with increasing doses of camptothecin alone resulted in a significant increase in the induction of apoptosis (P<0.01). However, co-treatment of the cells with 50 or 100 nM PGE(2) or 10 microM forskolin resulted in the inhibition of induction of the apoptotic pathway by camptothecin. These data demonstrate that PGE(2) inhibits apoptosis of epithelial cells possibly via cAMP-dependent pathway.     

Changes in the concentrations of plasma steroid hormone and plasma 13, 14-dihydro-15-oxo-prostaglandin F2 alpha in late pregnancy rabbits treated with an inhibitor of 3 beta-hydroxysteroid dehydrogenase

Changes in the concentrations of progesterone, 17 beta-estradiol and 13, 14-dihydro-15-oxo-prostaglandin F2 alpha (PGFM) were evaluated in the peripheral plasma of rabbits during late pregnancy by treating trilostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, in an attempt to obtain further insight into the involvement of progesterone and prostaglandin (PG) in the initiation of parturition. The concentrations of progesterone were 18.8 +/- 2.2 ng/ml (mean +/- SE, n = 6) before administration of the inhibitor, significantly (p less than 0.05) fell to 7.6 +/- 1.0 ng/ml (n = 6) at 30 min, and remained low until 10 h after the drug administration. The concentrations of progesterone were still low (5.4 +/- 0.5 ng/ml, n = 6) at 20-24 h after administration of the inhibitor, and were also low (4.9 +/- 2.2 ng/ml, n = 6) at delivery. Premature deliveries occurred at 28.8 +/- 2.0 h after injection of trilostane (on days 29 of gestation). Increased concentrations of PGFM were observed at delivery. However, administration of trilostane induced no discernible changes in the concentration of estradiol. These findings suggest that delivery is induced by progesterone withdrawal and that synthesis prostaglandin F2 alpha is remarkably increased at delivery in the rabbit.     

Oxytocin and estradiol concentrations in follicular fluid as a means for the classification of large bovine follicles

Large antral follicles (13 to 20 mm in diameter) were collected from ovaries of 109 cows and 17 heifers that also had a regressed corpus luteum at slaughter. Thirty percent of the animals had been injected once with prostaglandin F(2)alpha 48 hours before slaughter. Follicles were divided into 3 groups based on estradiol and oxytocin concentrations in the follicular fluid: Group I follicles, estradiol>/=100 ng/ml and oxytocin<65 pg/ml (preovulatory and assumed pre-gonadotropin surge); Group II follicles, estradiol<100 ng/ml and oxytocin>/=65 pg/ml (preovulatory and assumed post-gonadotropin surge); and Group III follicles, estradiol<100 ng/ml and oxytocin<65 pg/ml (atretic follicles). Treatment with prostaglandin F(2)alpha significantly increased the number of viable granulosa cells and estradiol content in Group I follicles. The estradiol: progesterone ratio was significantly higher in Group I vs Groups II and III, but it was similar for Group II healthy follicles and Group III atretic follicles. To ascertain the classification of follicles, PGF(2)alpha was administered on Day 6 of the cycle to induce corpus luteum regression, and a GnRH analog was administered 24 hours later. At 23 hours after GnRH analog treatment, follicular oxytocin levels significantly rose to 103 pg/ml. Concomitantly, estradiol concentrations fell to below 100 ng/ml. This response was not evident by 13 h after injection of the GnRH analog. The results indicate that follicular estradiol and oxytocin concentrations may be used as a means for the physiological classification of large bovine follicles.     

Effect of ovarian steroids and oxytocin on the production of prostaglandin E2, prostaglandin F2alpha and endothelin-1 from cow oviductal epithelial cell monolayers in vitro.

Cyclic physio-anatomical variation in the oviducts is mediated by the local countercurrent transfer of ovarian products. Thus, in this study cow oviductal epithelial cells (COEC) culture were utilized to investigate the effects of ovarian products such as progesterone (P4), estradiol 17beta (E2) and oxytocin (OT) on local oviductal prostaglandin E2 (PGE2), F2alpha (PGF2alpha) and endothelin-1 (ET-1) production. COEC were collected from non-pregnant Holstein cows (n = 8) during the follicular phase and cultured in M199 under standard culture conditions until monolayer formation. Cells in first passage were incubated for 24 or 48 h with P4 (500 ng/ml), E2 (1 ng/ml), OT (10(-9) M) or combination of E2 + P4. Administration of E2 significantly increased the production of PGE2, PGF2alpha and ET-1. However, simultaneous administration of P4 blocked the effect of E2. OT did not show any effect on oviductal productions of either PGs or ET-1. The results of this study show that E2 stimulates PG and ET-1 production by COEC in vitro. Thus, it can be suggested that locally transferred E2 from the ovarian follicles may be important for oviductal contraction and gamete/zygote transport during the peri-ovulatory period.     

Local changes in blood flow within the early and midcycle corpus luteum after prostaglandin F(2 alpha) injection in the cow

One of the postulated main luteolytic actions of prostaglandin (PG) F(2 alpha) is to decrease ovarian blood flow. However, before Day 5 of the normal cycle, the corpus luteum (CL) is refractory to the luteolytic action of PGF(2 alpha). Therefore, we aimed to determine in detail the real-time changes in intraluteal blood flow after PGF(2 alpha) injection at the early and middle stages of the estrous cycle in the cow. Normally cycling cows at Day 4 (early CL, n = 5) or Days 10--12 (mid CL, n = 5) of the estrous cycle (estrus = Day 0) were examined by transrectal color and pulsed Doppler ultrasonography to determine the blood flow area, the time-averaged maximum velocity (TAMXV), and the volume of the CL after an i.m. injection of a PGF(2 alpha) analogue. Ultrasonographic examinations were carried out just before PG injection (0 h) and then at 0.5, 1, 2, 4, 8, 12, 24, and 48 h after the injection. Blood samples were collected at each of these times for progesterone (P) determination. The ratio of the colored area to a sectional plane at the maximum diameter of the CL was used as a quantitative index of the changes in blood flow within the luteal tissue. Blood flow within the midcycle CL initially increased (P < 0.05) at 0.5-2 h, decreased at 4 h to the same levels observed at 0 h, and then further decreased to a lower level from 8 h (P < 0.05) to 48 h (P < 0.001). Plasma P concentrations decreased (P < 0.05) from 4.7 +/- 0.5 ng/ml (0 h) to 0.6 +/- 0.2 ng/ml (24 h). The TAMXV and CL volume decreased at 8 h (P < 0.05) and further decreased (P < 0.001) from 12 to 24 h after PG injection, indicating structural luteolysis. These changes were not detected in the early CL, in which luteolysis did not occur. In the early CL, the blood flow gradually increased in parallel with the CL volume, plasma P concentration, and TAMXV from Day 4 to Day 6. The present results indicate that PGF(2 alpha) induces an acute blood flow increase followed by a decrease in the midcycle CL but not in the early CL. This transitory increase may trigger the luteolytic cascade. The lack of intraluteal vascular response to PG injection in the early CL appears to be directly correlated with the ability to be resistant to PG.     

Administration of prostaglandin F2alpha after farrowing alters the association between lactation length and subsequent litter size in mid- or old-parity sows

A 4000 sow farm in the US using early weaning and a computerized record system was recruited. Farrowed sows were assigned into two experimental treatments: prostaglandin F2alpha injection or control. Sows were assigned by a farm worker to obtain even parity distributions between two groups in each farrowing group. A single i.m. injection of 2 ml of prostaglandin F2alpha between 24 and 48 h after farrowing was administered in the muscle immediately lateral to the vulva. Control sows received no treatment. Of 3562 farrowed sows, 1592 were administered with prostaglandin F2alpha. Parity distributions were not different between control and treatment groups. Parity was categorized into two groups: parity 1-2 or > or = 3. Mean lactation length was 18 days and there was no difference between the control and treatment groups. No main effects of prostaglandin F2alpha administration were found in either parity group on adjusted 21-day litter weight, weaning-to-first-mating interval or weaning-to-conception interval. In parity > or = 3 sows, a two-way interaction between the association of lactation length and treatment with pigs born alive at subsequent farrowing was found (P = 0.044), while no such interaction was found in parity 1-2 sows (P = 0.14). The prediction line for subsequent pigs born alive indicates that prostaglandin F2alpha administration alters the relationship between lactation length and subsequent litter size on mid- or old-parity sows.     

Effect of prostaglandin F2 alpha at different stages of guinea-pig pregnancy

It is believed that suppression of the processes by which prostaglandin F2 alpha is released from the uterus during the estrous cycle is vital to maintenance of pregnancies in guinea-pigs. Prostaglandin F2 alpha was injected into pregnant guinea-pig at four different stages of gestation to investigate the effect increased prostaglandin might have. The study revealed an alteration in the sensitivity of the pregnancy to prostaglandin F2 alpha as pregnancy progressed. Recovery from the prostaglandin insult was more likely if the injection was given after Day 24 than before Day 18. In some animals the serum progesterone levels fell following the injection and then subsequently recovered. It appears that effects which are potentially hazardous to the pregnancy are countered in a variety of ways.     

Observations on the use of prostaglandin F(2alpha) as an abortifacient and effect of gonadotrophin-releasing hormone on ovarian activity after induced abortion during the breeding season in goats

Results of two experiments are described. In the first experiment, forty-one mixed-breed goats (does) with unknown gestation lengths were given 10 mg prostaglandin F(2alpha) (PGF(2alpha)) (2 doses of 5 mg each, 24 h apart) i.m. Blood samples were obtained before each treatment with PGF(2alpha) by jugular venipuncture, and plasma progesterone (P(4)) concentrations were determined by a nonextraction solid-phase radioimmunoassay. P(4) concentrations (ng/ml) were significantly decreased (15.47 vs 1.55, P<0.005) 24 h after the first injection of PGF(2alpha). A total of 63 fetuses was collected within 46.5 h following the first injection. Mean (+/- SE) crownrump lengths and body weights of 62 fetuses were 21.46 +/- 0.29 centimeters (cm) and 575.00 +/- 20.60 g, respectively. Based on these findings, the mean gestation length of these does was estimated to be 86.96 +/- 0.74 d. Thirty-one does retained their placenta for 12 to 72 h and were treated with a single injection of 5 mg PGF(2alpha) and 800 mg oxytetracycline i.m. Placental expulsion in all does occurred within 24 h posttreatment. The results of this study suggest that two doses of 5 mg PGF(2alpha) intramuscularly (i.m.) 24 h apart is an effective abortifacient at about 3 mo of pregnancy in does. In the second experiment, 38 does from the first experiment were divided in two groups of 19 each on Day 13 postabortion. Group A (treated) was given 50 ug GnRH i.m. while Group B (control) received 1 ml 0.9% saline i.m. Blood samples were obtained prior to treatment and on Day 23 postabortion and assayed for P(4) concentrations. There was no significant difference (P>0.10) in P(4) concentrations of samples obtained pre- and post-GnRH treatment. However, 14 of 19 and 12 of 19 in Groups A and B, respectively, exhibited estrus within 52 days following abortion. Twenty-six does were bred naturally and 17 became pregnant.