F2 Alpha Metabolite Research Articles

Can Non-invasive Hormone Profiling in Female Tigers (Panthera tigris) could Differentiate True Pregnancy and Pseudopregnancy

Background: The tigers (Panthera tigris) being the world’s largest cat are one of the critically endangered species which are at the verge of extinction. The pseudopregnancy or false pregnancy or pseudocyesis is a syndrome which is characterized by the presence of signs of pregnancy in a non-pregnant animal. False lactation or nervous lactation are the terms which are used to refer pseudopregnancy as there is very low quantities of milk production is seen. This condition can be differentiated with true pregnancy by using hormones and by correlation of behavioral symptoms of pregnancy with hormonal profiles for confirmation of pregnancy in female tigers. Methods: Total seven animals were used in the experiment and was divided into three groups (G I, G II and G III). Group G I consist of 03 non-bred animals of less than 9 years of age, G II consisted of 03 non-bred animals of more than 9 years of age and G III was consisted of 03 animals after mating irrespective of their age. Faecal samples were collected non-invasively from enclosures weekly up to 14 weeks. Only fresh samples (deposited within 24 h) was chosen, urine puddles were aspirated from the floor. The extracted samples were then analysed for estimation of relaxin, progesterone and prostaglandin F2 alpha metabolite (PGFM) by enzyme linked immunosorbent assay (ELISA). Result: Relaxin the hormone for early detection of pregnancy in felines gives elevated concentration from 49 days after mating and attains a peak during parturition, whereas, no elevation or peak was observed in pseudopregnant animals. Progesterone, in true pregnancy remains elevated from 7th week onwards after mating, it gets dropped after 7th week with wide fluctuation in pseudopregnant animals. PGFM elevation observed after nine weeks of gestation in true pregnancy whereas, no elevation will be observed in pseudopregnant tigress.

Meloxicam and Dexamethasone Administration as Anti-Inflammatory Compounds to Sows Prior to Farrowing Does Not Improve Lactation Performance.

Simple SummarySows may experience pain and discomfort whilst giving birth. Additionally, the birthing process is accompanied by an inflammation response. Administering anti-inflammatory compounds prior to birth may provide an opportunity to improve piglet survival and growth. The aim of this experiment was to assess the efficacy of both a non-steroidal (NSAID; meloxicam) and steroidal (SAID; dexamethasone) anti-inflammatory drug for improving farrowing house performance of sows. In younger sows, there was no impact of treatment; however, older sows from the NSAID treatment gave birth to fewer live piglets. Postnatal mortality was unaffected by treatment and no improvement in piglet growth was observed. Feed intake of both NSAID and SAID sows was improved when compared with the control group; however, there was a tendency for a delayed oestrus in the NSAID group. Administering NSAID to sows prior to farrowing is not recommended as it reduces piglet survival and subsequent reproduction.The aim of this experiment was to determine whether administration of an anti-inflammatory compound to sows prior to farrowing would, via reduced pain and inflammation, increase piglet survival and growth. At day 114 of gestation, multiparous sows were randomly allocated to one of the following treatments: Control (n = 43), which received 10 mL saline, NSAID (n = 55) which received 0.4 mg/kg meloxicam and SAID (n = 54) which received 0.1 mg/kg dexamethasone. Treatments were applied again on day 116 if farrowing had not occurred. There was no treatment effect on piglets born alive or dead from parity two to four sows but in those of parity five and older, NSAID administration reduced the number of piglets born alive and increased the number of piglets born dead (p < 0.05). Sow rectal temperature and incidence of mastitis were unaffected by treatment (p > 0.05). Lactation day two plasma concentrations of cortisol, prostaglandin F2 alpha metabolite and haptoglobin did not differ among treatments (p > 0.05). Treatment effects were not observed in liveborn piglet mortality at any age, or litter weight at day 21 (p > 0.05). Average feed intake during lactation was increased by both NSAID and SAID treatments (p = 0.001). The use of meloxicam prior to farrowing should be avoided as it reduced the number of piglets born alive and did not improve piglet survival and growth.

Effects of lipoic acid supplementation on activities of cyclooxygenases and levels of prostaglandins E2 and F2 alpha metabolites, in the offspring of rats with Streptozotocin-induced diabetes

Effects of lipoic acid supplementation on activities of cyclooxygenases and levels of prostaglandins E2 and F2 alpha metabolites, in the offspring of rats with Streptozotocin-induced diabetes

Pulsatility and Interrelationships of 13,14-Dihydro-15-Keto-PGF2alpha (PGFM), Luteinizing Hormone, Progesterone, and Estradiol in Heifers1

Temporality among episodes of a prostaglandin F2alpha metabolite (PGFM), progesterone (P4), luteinizing hormone (LH), and estradiol (E2) were studied during preluteolysis and luteolysis. A vehicle group (n = 10) and a group with an E2-induced PGFM pulse (n = 10) were used. Blood sampling was done every 0.25 h for 8 h. An episode was identified by comparing its coefficient of variation (CV) with the intra-assay CV. Pulsatility of PGFM, P4, LH, and E2 in individual heifers was inferred if the autocorrelation functions were different (P < 0.05) from zero. About four nonrhythmic fluctuations of PGFM/8 h were superimposed on PGFM pulses. Pulsatility was detected for LH but not for P4 and E2. A transient increase in P4 was not detected during the ascending portion of a PGFM pulse. Progesterone decreased (P < 0.003) during Hours -1.25 to -0.50 of the PGFM pulse (Hour 0 = peak) and ceased to decrease temporally with an increase (P < 0.05) in LH. Maximum P4 concentration occurred 0.25 h after an LH pulse peak, and an increase (P < 0.005) in E2 began at the LH peak. Nadirs of LH pulses were greater (P < 0.05) and the nadir-to-nadir interval was shorter (P < 0.003) in the E2 group, which is consistent with reported characteristics during luteolysis. The results did not support the hypothesis of a transient P4 increase early in a PGFM pulse and indicated a balance between a luteolytic effect of PGF and a luteotropic effect of LH within the hours of a PGFM pulse.

Characteristics of Pulses of 13,14-Dihydro-15-Keto-Prostaglandin F2alpha Before, During, and after Spontaneous Luteolysis and Temporal Intrapulse Relationships with Progesterone Concentrations in Cattle1

Pulses of the prostaglandin F2alpha (PGF) metabolite 13,14-dihydro-15-keto-PGF (PGFM) were compared among heifers that were in the preluteolytic, luteolytic, and postluteolytic periods (n = 7 or 8 heifers/period). Hourly blood sampling was done in 18-h sessions 15, 16, or 17 days after ovulation. Hourly sampling and statistical identification of a PGFM pulse allowed novel comparisons of PGFM pulses among the three periods. Each period had a similar number of PGFM pulses (2.3 +/- 0.2). The pulses were more prominent during the luteolytic period than during the other periods, as indicated by significantly greater concentration for the peak and amplitude between nadir and peak. Significantly more fluctuations that did not meet the definition of a pulse occurred at the beginning of the preluteolytic period and end of the postluteolytic period than during the luteolytic period. The same nadir ended a pulse and began the next pulse in 85% of adjacent pulses. Seven heifers were selected objectively, based on a progesterone concentration >5 ng/ml at Hour -3 (Hour 0 = peak of PGFM pulse) and a progressive decrease in progesterone from Hours -3 to 0. Progesterone increased (P < 0.03) between Hours 0 and 1, remained at a mean plateau at Hours 1 and 2, and then decreased. Results support the hypothesis of a transient intrapulse rebound in progesterone during an individual PGFM pulse, but only during the first portion of luteolysis. These findings should be considered in future proposals on the mechanisms involved in the effects of PGF on progesterone concentrations.

Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite), progesterone and oestradiol (E2-17β) levels were analysed.The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

Delay of preterm birth in sheep by THG113.31, a prostaglandin F 2α receptor antagonist

A novel prostaglandin F2alpha receptor antagonist, THG113.31, was tested for the suppression of uterine contractility and delay of preterm labor in sheep. We determined the tocolytic effectiveness of THG113.31 on contractions that were stimulated in vitro by prostaglandin F2alpha and E2 in longitudinal and circular myometrial strips. We also tested the ability of THG113.31 in vivo to lower uterine electromyographic activity that was induced by the progesterone receptor blocker, RU486, and to delay preterm birth. THG113.31 suppressed the amplitude of prostaglandin F2alpha, but not prostaglandin E2-induced contractions of both circular and longitudinal myometrium (P<.01). The times to delivery after RU486 were 34.8+/-1.1 hours (saline solution) and 41.9+/-0.5 hours (THG113.31; P<.001) or an average delay of 7.1 hours. There were no changes in fetal blood gases (PaO2 , PaCO2 , pH, or SaO2) because of THG113.31. Fetal cortisol levels rose in each group, and fetal and maternal prostaglandin E2 and F2alpha metabolite concentrations rose similarly in both groups. THG113.31 specifically suppresses prostaglandin F2alpha-induced myometrial contractility and delays delivery.

Effects of repeated follicular punctures on ovarian morphology and endocrine parameters in dairy heifers.

Three experimental and three control heifers were included in the study. After a control period (CP), the experimental heifers were subjected to 4 and 5 weeks of twice-weekly follicular punctures (FPP1 and FPP2) with two oestrous cycles in between. The follicular punctures were performed using the ovum pick-up (OPU) technique. During the CP and FPPs, ovarian activity was monitored by transrectal ultrasonography and analyses of plasma progesterone, prostaglandin F2alpha (PGF2alpha) metabolite, luteinizing hormone (LH), oestradiol and follicle stimulating hormone (FSH) levels. The animals were slaughtered 7 days after cessation of FPP2 and their ovaries examined. The control animals were monitored for their oestrous cyclicity and were then ovariectomized and the ovaries examined. Despite the absence of ovulation, the formation of corpus luteum (CL)-like structures could be ultrasonographically observed during FPPs. These structures either had characteristics comparable to those of the CLs during the CP (group 1) or were smaller and had a shorter life span and (or) luteal active phase with a lower progesterone production (group 2). In group 1, CL-like structures emanated from punctures of large-sized follicles on or close to the days on which the animals showed oestrus and had a rise in oestradiol and LH. In group 2, the structures developed from punctures of smaller-sized follicles and no oestrus nor a detectable 1.14 rise was revealed around punctures. During most FPPs, the basal level of LH was at zero. During all FPPs, a significant rise in FSH level occurred on the day following the day of puncture. To conclude, repeated follicular puncture appeared to alter slightly endocrine profiles and cause minor morphological changes in the ovaries. Both the macro- and microscopic examinations revealed the presence of luteal structures and follicles of various sizes in the ovaries of all heifers studied. The connective tissue in the ovarian tunica albuginea of the experimental heifers was significantly thicker than that in controls (P < 0.001).

Impact of Postovulatory Food Deprivation on the Ova Transport, Hormonal Profiles and Metabolic Changes in Sows

The effect of food deprivation on ova transport, hormonal profiles and metabolic changes was studied in 20 crossbred multiparous sows during their second oestrus after weaning. To determine the time of ovulation, transrectal ultrasonographic examination was performed. The sows were divided into 2 groups, one control group (C-group), which was fed according to Swedish standards, and one experimental group (E-group). The E-group sows were deprived of food from the first morning meal after ovulation until slaughter. Blood samples were collected every second hour from about 12 h before expected ovulation in the second oestrus after weaning until slaughter and were analysed for progesterone, prostaglandin F2α-metabolite, insulin, glucose, free fatty acids and triglycerides. All sows were slaughtered approximately 48 h after ovulation and the genital tract was recovered. The isthmic part of the oviduct was divided into 3 equally long segments and flushed separately with phosphate buffered saline (PBS). Uterine horns were also flushed with PBS. A significantly greater number of ova were found in the first and second part of the isthmus in the E-group (p = 0.05) while in the C-group most of the ova were found in the third part of the isthmus or the uterus (p = 0.01). The level of prostaglandin F2α-metabolite was significantly higher in the E-group compared with the C-group. The concentration of progesterone increased in both groups after ovulation but there were no significant differences between the groups. The other blood parameters showed that the food-deprived sows were in a catabolic state. The 48 h period of fasting results, directly or indirectly in an delayed ova transport, which may be due to a delayed relaxation in the smooth circular muscle layer of the isthmus.

Bovine viral diarrhoea virus: its effects on ovarian function in the cow.

Bovine viral diarrhoea virus (BVDV) is a major cattle pathogen responsible for a spectrum of symptoms, including reproductive failure. In this paper we investigate how BVDV interacts with the ovary. The viruses' tropism for the pre-ovulatory oocyte was studied by indirect immunohistochemistry. Two monoclonal antibodies, raised against the non-structural protein NS3 and the envelope glycoprotein E2 were used to probe cryo-sections cut from the ovaries of three persistently infected heifers. NS3 and E2 antigens were widely distributed within the ovarian stroma and follicular cells. NS3 was also localised within the proportion of oocytes. Overall 18.7% of the oocyte population had detectable levels of NS3. What is more, the proportion of antigen positive oocytes remained constant (P>0. 05) throughout the different stages of oocyte maturation. In a subsequent study seven cows were challenged with non-cytopathogenic BVDV (strain Pe515: 5x10(6) TCID(50)) to determine the oestradiol and progesterone responses to an acute infection. The sensitivity of the endogenous luteolytic mechanism was also established by analysing plasma prostaglandin F2alpha metabolite (PGFM) levels following an exogenous oxytocin (50 IU) challenge. The inoculation was given 2 days before a synchronised oestrus and was timed to ensure that viraemia occurred during the initial stage of corpora luteal development. Seven cows inoculated with non-infectious culture medium served as control animals and remained BVDV naive throughout the study. The BVDV challenge was followed by leucopenia, viraemia and sero-conversion. The virus also significantly (P<0.01) reduced plasma oestradiol levels between day 6 and day 11 post-inoculation (i.e. between day 4 and day 9 post-oestrus). However, the infection did not alter (P>0.05) progesterone secretion throughout the oestrous cycle or the plasma concentration of PGFM. These data indicate that bovine follicular cells and oocytes are permissive to BVDV at all stages of follicular development. They also show that a transient fall in oestradiol secretion may accompany an acute infection. In conclusion, this work has identified two potential routes through which BVDV can reduce fertility in the cow, namely impairment of oocyte quality and disruption of gonadal steroidogenesis.

Metabolism of prostaglandin F2alpha during fasting in prepubertal gilts.

The study was conducted to investigate a possible mechanism behind earlier observations of fasting-induced increases of blood concentrations of prostaglandin (PG) F2alpha metabolite (P-PG) in gilts. Six animals were fasted for 28 h, then administered i.v. PGF2alpha (500 ng/kg body weight). Blood samples were withdrawn at 1, 3, 5, 7, 10, 15, 20, 30, 40, 60 min, 2 and 3 h after the injection. A control group followed an identical protocol, except that they were fed during the corresponding 28 h-period. P-PG increased as previously observed during the 28 h of fasting. The P-PG increase in terms of area under the concentration time curve (AUC) following injection was significantly larger in the fasted than in the non-fasted gilts. In the fasted animals, the mean P-PG maximum concentration (Cmax) was 7145 pmol/L, the corresponding value for the non-fasted animals was 4566 pmol/L. PGs are metabolised through beta-oxidation in the liver. The results of this study imply that reduced 15-ketodihydro-PGF2alpha breakdown in the liver might contribute to the fasting-induced increases in P-PG.

Plasma levels of cortisol, progesterone, oestradiol-17 beta and prostaglandin F2 alpha metabolite after ACTH (Synacthen Depot) administration in ovariectomized gilts.

In order to elucidate the effect of stress on reproductive hormones, the present study was designed to investigate the effect of adrenocorticotropic hormone (ACTH) on the plasma levels of cortisol, progesterone, oestradiol-17 beta and prostaglandin F2 alpha metabolite in ovariectomized gilts. Ovariectomy and cannulation of the jugular vein were performed within 1 week of oestrous detection, under general anaesthesia. Approximately 1 week after surgery, two gilts were each administered ACTH (Synacthen Depot) intravenously, at a dose of 0.01 mg/kg body weight, and one gilt was given saline solution (5 ml). The reverse was performed on the following day. The administration of ACTH was followed by a concomitant elevation of cortisol, progesterone and prostaglandin F2 alpha metabolite but not of oestradiol-17 beta. Peak cortisol, progesterone and prostaglandin F2 alpha metabolite levels were reached at 80 +/- 10.0, 80 +/- 10.0 and 46.6 +/- 13.3 min after ACTH administration and the durations of the peaks were 181.8 +/- 19.8, 308.1 +/- 49.7 and 181.8 +/- 7.9 min, respectively. The total area under the curve for cortisol, progesterone and prostaglandin F2 alpha metabolite was significantly higher in the ACTH than in the control group. The present results indicate that during stress, cortisol, progesterone and prostaglandin F2 alpha levels are elevated while the level of oestradiol-17 beta is less affected. It can be concluded that the administration of ACTH to ovariectomized gilts, results in the elevation of cortisol, progesterone and prostaglandin F2 alpha metabolite but not of oestradiol-17 beta.

Plasma fatty acids, prostaglandin F2alpha metabolite, and reproductive response in postpartum heifers fed rumen bypass fat.

An experiment was conducted to determine whether feeding rumen-protected fatty acids (FA) to postpartum heifers would increase plasma concentrations of linoleic acid and PGF2, metabolite (PGFM), shorten the interval from calving to first increase in plasma concentrations of progesterone (P4), and increase pregnancy rate relative to controls. Hereford x Angus heifers (346 kg) were assigned randomly to treatments containing either lipid or barley supplemented diets for the first 30 d postpartum. Lipid was .23 kg.heifer(-1).d(-1) of calcium salts of FA (CSFA; n = 20), and an isocaloric amount of barley served as the control (n = 19). Supplements, with .23 kg of barley as a vehicle, and a basal diet of meadow and alfalfa hays were pen fed to heifers (5/pen). Heifers were bled on alternate days (d1 to 30) and twice weekly (d 30 to 2 wk after first estrus) for RIA of plasma PGFM and P4, respectively. Weight percentage of major FA in plasma on d1 and 7 was determined with gas chromatography. First behavioral estrus was detected by use of intact bulls and confirmed by an increase in plasma P4. On d 7, but not d 1, plasma from heifers fed CSFA had altered proportions of major FA (P < .01), including an increase in linoleic acid compared with those of controls (29.1 vs 25.6% of total FA; SE = .75; P < .01). Analysis of variance of contrast variables revealed an effect of treatment on direction of change in PGFM from d 3 to 5 (P < .01). By d 7 and on d 9, plasma concentrations of PGFM were greater in heifers fed CSFA than in controls (P = .02 and P = .06, respectively). There was no difference in plasma concentration of PGFM between treatments on d 1, 3, 5, 11, 13, and 15 postpartum (P = .80, .17, .52, .82, .46, and .77, respectively). Days to first estrus with ovulation, pregnancy rate, and calving interval were not affected by treatments (P = .58, .52, and .24, respectively). Although supplemental lipid fed to primiparous beef heifers increased plasma levels of linoleic acid and production of PGFM in the early postpartum period, it did not improve the fertility of these heifers in the subsequent breeding season.

Effect of sodium cloprostenol and flunixin meglumine on luteolysis and the timing of birth in bitches.

At birth, the physiological role of prostaglandins in bitches is unclear. Bitches were treated before parturition with either saline, the prostaglandin analogue, sodium cloprostenol, or the prostaglandin synthetase inhibitor, flunixin meglumine. The animals were examined regularly to determine the onset of parturition and a series of blood samples were taken to define the hormonal profiles before, during and after birth. Animals treated with cloprostenol whelped earlier than did controls. In addition, the prostaglandin F2 alpha metabolite surge and decrease in plasma progesterone concentration and rectal temperature were earlier than in controls. Flunixin meglumine disrupted the normal 13,14-dihydro-15-keto prostaglandin F2 alpha profile but did not abolish prostaglandin synthesis completely or delay the onset of labour in treated animals. This study confirms that prostaglandins induce luteolysis and the onset of labour in the bitch. However, the partial inhibition of prostaglandin synthesis does not prevent parturition.

Expression of monocyte chemoattractant protein-1 in the bovine corpus luteum around the time of natural luteolysis.

Monocyte chemoattractant protein (MCP-1) is a specific chemoattractant for monocytes/macrophages that could have a role in the influx of macrophages into the corpus luteum (CL) during structural luteolysis. In this study, reverse transcription-polymerase chain reaction and in situ hybridization were used to investigate MCP-1 mRNA expression in CL collected from 18 heifers between Days 15 and 20 of the estrous cycle. There was expression of mRNA encoding MCP-1 in luteal tissue from all cows; however, expression was greater in animals that had undergone luteolysis at the time of CL collection as compared to animals in which the CL was still functional. Similarly, in situ hybridization showed greater expression of mRNA encoding MCP-1 in CL after functional luteolysis. There was also evidence of increased MCP-1 mRNA expression in an animal with a functional CL where the systemic concentration of prostaglandin F2alpha metabolite was high at the time of tissue collection. T lymphocyte populations, identified by immunohistochemistry, had a distribution similar to that of cells expressing MCP-1 mRNA within the CL, but other cell types were also involved. These results demonstrate an increase in MCP-1 mRNA after functional luteolysis in the cow, which may be related to the influx of macrophages that occurs at this time.

Effects of post-ovulatory food deprivation on oviductal sperm concentration, embryo development and hormonal profiles in the pig.

Nutrition is one of the multiple factors that modulate reproduction in animals. The effect of 48 h food deprivation on reproductive and metabolic hormonal changes in relation to cleavage rates was studied. Insemination of 15 sows was performed 20-10 h prior to expected ovulation and ova were recovered at slaughter 65-91 h post ovulation. Blood samples were collected every second hour, beginning from the time of insemination until slaughter, for measurements of progesterone, cortisol, the prostaglandin F2alpha metabolite (15-keto-13,14-dihydro-PGF2alpha) and insulin levels. The embryos from the food-deprived sows (D-group) had fewer accessory spermatozoa in their zona pellucida (ZP) compared with the control sows (C-group). A lower cleavage rate of the embryos in the D-group compared with the C-group was detected. Plasma progesterone, cortisol and prostaglandin F2alpha metabolite levels were significantly higher in the D-group compared with the C-group. Food deprivation is associated with changes in reproductive and metabolic hormones that might lead to changes in the oviductal environment, culminating in a lower cleavage rate of the embryos and presence of fewer viable spermatozoa in the reservoir.

Stimulation of ovarian oxytocin secretion and uterine prostaglandin release by exogenous progesterone early in the cycle of the ovarian auto-transplanted ewe.

The present study was undertaken to determine whether the administration of progesterone, early in the oestrous cycle, had an influence on ovarian oxytocin secretion and on peripheral concentrations of the prostaglandin F2 alpha metabolite 13,14-dihydro-15-keto PGF2 alpha (PGFM) in the ovarian auto-transplanted ewe. Twelve ewes with ovarian auto-transplants (n = 6 per group) were randomly assigned to receive an i.m. injection of progesterone (12.5 mg) or vehicle, twice a day, on days 1, 2 and 3 of the oestrous cycle. Beginning on day 7, blood samples were collected at intervals of 1 h from the ovarian and contralateral jugular veins for up to 70 h. Ovarian oxytocin secretion rate and jugular concentrations of PGFM and progesterone were determined by radioimmunoassay. The number of ewes that showed pulses of both ovarian oxytocin and PGFM was significantly (P < 0.05) greater in progesterone-treated ewes than in control ewes. In progesterone-treated ewes, the average number of ovarian oxytocin pulses per ewe was 9.66 +/- 5.5 (mean +/- SD) and the interval between pulses was 7.18 +/- 5.8 h. The mean amplitude and amount of oxytocin released, as calculated by the area under the curve of ovarian oxytocin pulses, were 6.27 +/- 1.98 ng min-1 and (10.05 +/- 8.91 ng min-1)tau, respectively (where tau is the number of hours between the last time point before and the first time point after a significant increase in hormone concentration was detected by the Pulsar program). The mean amplitude and area under the curve of PGFM pulses were 317.22 +/- 5.65 pg ml-1 and (383.36 +/- 1.77 pg ml-1)tau, respectively. The average number of pulses of plasma PGFM observed per ewe was 5.8 +/- 1.9 and interpulse interval for plasma PGFM pulses was 10.32 +/- 8.7 h between day 7 and day 9 after oestrus. These data indicate that administration of progesterone during the first 3 days of the oestrous cycle results in the premature release of ovarian oxytocin and uterine prostaglandin F2 alpha.

Effect of pregnancy and exogenous interferon on synchronous pulsatile release of oxytocin and luteolytic prostaglandin F2 alpha in red deer (Cervus elaphus).

Three experiments were carried out to investigate the secretion of luteolytic hormones in red deer hinds during the oestrous cycle, early pregnancy and after administration of interferon, the putative pregnancy recognition signal. Three groups of hinds (n = 8-9 per group) were treated with progesterone-impregnated intravaginal controlled internal drug releasing (CIDR) devices for 13 days (device withdrawal = day 0). Group 1 (n = 9) served as controls; Group 2 (n = 8) received injections of 4 mg recombinant bovine interferon-alpha 1 l twice a day on days 13-18; Group 3 (n = 9) were run with a fertile stag on days 0-3. Plasma samples collected each day on days 16-23 were analysed for progesterone. Plasma samples collected each hour for 16 h on days 4, 10, 16, 18 were analysed for oxytocin and the prostaglandin F2 alpha (PGF2 alpha) metabolite (PGFM). Plasma progesterone concentrations declined to < 1 ng ml-1 between days 18 and 25 in control hinds indicating that luteolysis had occurred, whereas there was no endocrine evidence of luteolysis in interferon-treated or pregnant hinds. Control hinds (6/9) exhibited synchronous pulses of oxytocin and PGF2 alpha secretion on day 18, a greater proportion than on any other day in these hinds or on any day in the interferon-treated or mated hinds (P < 0.05). In a second experiment, close synchrony in secretion of oxytocin and PGF2 alpha pulses was evident in an unmated hind when samples were collected every 12 min on day 18. In a third experiment, oxytocin-induced PGF2 alpha secretion was potentiated by oxytocin administration at an interval of 1 h and inhibited by administration at a 6 h interval (P < 0.05). These results suggest that synchronous pulsatile secretion of oxytocin and PGF2 alpha induces luteolysis and is suppressed by pregnancy or administration of interferon. Oxytocin-induced alterations in uterine oxytocin sensitivity may underlie the pulsatile nature of luteolytic hormone secretion in red deer.

Oxytocin antagonist [1-D(CH2)5,Tyr(ME)2,Thr4,Tyr-NH2(9)]ornithine vasotocin inhibits oxytocin-induced prostaglandin F2alpha release in late-pregnant cows.

The affinity and specificity of an antagonist of oxytocin, [1-D(CH2)5,Tyr(ME)2,Thr4,Tyr-NH2(9)]ornithine vasotocin (OTA), to oxytocin receptors (OTR) in bovine gestational endometrium was determined in displacement experiments with oxytocin (OT) and vasopressin (AVP) analogues and compared to myometrial OTR. OTA had the highest affinity in both tissues. The effect of OTA on OT-induced increase in plasma concentration of 13,14-dihydro-15-keto-prostaglandin F2alpha metabolite (PGFM) was studied in 24 late-pregnant cows. Treatments consisted of i.v. saline; OT (50 IU); OTA (1200 microg); and OTA (400, 1200, or 4000 microg) injected i.v. 5 min before OT (50 IU) (n = 4 each). Samples were collected from jugular vein at 15-min intervals for 30 min before and 3 h after the injection of OT. Progesterone was measured in once-daily samples taken for 7 days after the experiment. OT caused a twofold increase in plasma PGFM within about 60 min (p < 0.005), with levels returning to baseline at 150-180 min; OTA (1200 microg) caused a gradual lowering of basal plasma PGFM over 180 min (p < 0.05). The 400-microg or 1200-microg dose of OTA did not alter OT-induced PGFM response, whereas the 4000-microg dose inhibited it almost completely (p < 0.005). Plasma progesterone declined after the experiment in all cows, with no differences among groups. Because OTA inhibits OT-induced release of endometrial prostaglandin F2alpha it may be a good tocolytic agent.

Intravascular infusion of lipid into ewes stimulates production of progesterone and prostaglandin.

Effects of infusion of a lipid emulsion into ewes during mid-to late diestrus on serum concentrations of total cholesterol (TC), progesterone (P4), prostaglandin (PG) F2 alpha metabolite (PGFM), and PGE2, and on ovulation rate were examined. In experiment 1, ewes received infusions of either saline (S, n = 3) or soybean oil emulsion (SB, n = 3) for 5 h on each of Days 9-13 of the estrous cycle. In experiment 2, ewes received infusions of either S (n = 4), SB (n = 5), or olive oil emulsion (OO, n = 5) for 5 h on each of Days 9 through 15 of the estrous cycle. In both experiment 1 and experiment 2, infusion of lipid increased serum concentrations of TC and P4, which declined with time after infusion was terminated (treatment x hour interaction, experiment 1: TC, p < 0.01, P4, p < 0.01; experiment 2: TC, p < 0.01, P4, p < 0.001). Serum PGFM and PGE2 concentrations were greater in lipid-infused ewes than in controls on Days 13 through 15 (treatment x hour interaction; p < 0.03, p < 0.001, respectively). Duration of the estrous cycle was shortened in OO-infused ewes (16.2 +/- 0.4 days) compared with that of SB- and S-infused ewes (17.2 +/- 0.2 and 18.0 +/- 0.0 days, respectively; p < 0.01). Numbers of corpora lutea and follicles, and diameter of follicles > 4 mm did not differ among treatment groups on Day 14 of the succeeding cycle after infusion. These data indicate that lipid infusion stimulated increases in serum concentrations of TC, P4, and prostaglandins and may shorten the estrous cycle.