2α Analogue Research Articles

Social behaviour at and around oestrus of N'dama cows treated with prostaglandin F 2α analogue, Cloprostenol

Fourteen N'dama cows treated with Cloprostenol, a prostaglandin F 2α (PGF 2α) analogue, were observed for social and oestrus behaviour. The cows were given two intramuscular injections of PGF 2α 11 days apart and were then observed continuously 18 h after each injection (treatment) for 7 days. The proportion of cows showing standing oestrus were 85.7% and 92.9% in Treatments 1 and 2, respectively. Agonistic behaviours (threats, butts and fights) declined significantly ( P<0.05) while amicable behaviours (play) significantly increased between Treatments 1 and 2. Mounting activity and duration of oestrus significantly increased while sniffing, licking and rubbing activities significantly declined between the two treatments. Dominance Value (DV) and Index of Dominance Activities (DAI) determined within each treatment were not stable across treatments. Live weight, but not age was significantly ( P<0.05) correlated with DV ( r=0.542–0.647) and DAI ( r=0.588–0.634). There was a strong allelomimetic tendency in the herd with animals forming a cohesive group most times during grazing and resting. Within this group some cows were strongly attached to each other and this was not disturbed by oestrus. Neither agonistic interactions received nor DV or DAI were significantly correlated with mounts received or oestrus duration. Cows coming into oestrus around the same time tended to be preferred mounting associates.

Effects of a prostaglandin F 2α analogue on the ovulatory response of superovulated heifers

Thirty-one cycling heifers were superovulated and subsequently ovanectomized to determine if preovulatory follicles could be induced to ovulate by the administration of cloprostenol, a potent agonist of prostaglandin F 2α. Superovulation was induced, during the mid-luteal phase, with a total dose of 20 mg porcine pituitary extract of follicle stimulating hormone (FSH) given twice daily over 4 days in decreasing doses; a luteolytic dose of cloprostenol was administered on the third day. Two experiments were carried out in which ovariectomies (OVX) were performed at 64 h following cloprostenol injection. Owing to the variable interval between the preovulatory peak of luteinizing hormone (LH) and OVX observed in Experiment I, the preovulatory LH surge was induced in Experiment II by 100 μg of a synthetic analogue of gonadotropin releasing hormone (GnRH) given 36 h after the luteolysin. To test the hypothesis that cloprostenol is able to induce, enhance or synchronize ovulation, two different doses of this hormone, 1.25 or 2.5 mg, were injected at 4 and 2 h or at 2 and 1 h prior to OVX. Plasma progesterone (P 4) and LH concentrations and follicular fluid P 4: estradiol-17β (E 2) ratios in the non-ovulated follicles were utilized to identify animals that had a typical response to the superovulatory treatment and, at OVX, total number of follicles 8 mm or more in diameter, and number of ovulations were recorded. When data from both experiments were considered, it was observed that: (1) GnRH injection did not affect ovulation rate; (2) cloprostenol injections induced more follicles ( P < 0.01) to ovulate, 59.3% vs. 20.1%, SE = 9.8, in cloprostenol-treated vs. controls, respectively, at the time tested; (3) cloprostenol dose had a positive linear effect ( P < 0.01) on ovulation rate. In conclusion, the data suggest that prostaglandin F 2α or its analogues could be used to induce a more synchronous ovulation of follicles in superovulated heifers.

Effects of induction of parturition by administration of a prostaglandin F 2α analogue in rabbits: possible modification of prolactin, LH and FSH secretion patterns

The influence of inducing parturition by the administration of prostaglandin F 2α (PGF 2α) on prolactin (PRL), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion patterns during the last days of pregnancy (Days 29–31) and lactation (Days 1–28) was studied in 20 doe rabbits of the California breed. Animals were allocated to receive either a single intramuscular injection of 50 μg of a PGF 2α, analogue (treated group) or 2 ml saline (control group) on Day 29 of pregnancy. All females were mated on Day 7 post-partum. The conception rate in treated and control animals was 100% and 90%, respectively. No influence of the prostaglandin treatment on mean plasma PRL and FSH concentrations was observed. High plasma PRL levels were detected in both groups from Day 7 to 19 of lactation. PRL levels decreased in all rabbits from Day 19 to 28 of lactation. Prostaglandin F 2α-treatcd animals showed low plasma LH concentrations after treatment during the entire period studied. High mean FSH concentrations were found in both groups from Day 3 to 5 and 19 to 28 of lactation, and low levels from Day 7 to 16 of lactation. The results suggest that the induction of parturition by PGF 2α can influence the final stage of pregnancy and lactation period due to changes in plasma LH levels, and has no effect on mean plasma PRL and FSH levels during these same periods.

Prostaglandin-induced secretion of oxytocin and prolactin in red ( Cervus elaphus) and Pere David's ( Elaphurus davidianus) deer hinds: Evidence for oxytocin of luteal origin

Peripheral plasma concentrations of oxytocin in female red deer during the luteal phase of the oestrous cycle (9.3 ± 2.1 fmol/ml) exceeded those in the follicular phase (3.1 ± 1.4) or during seasonal anoestrus (3.2 ± 1.3). In both red and Père David's deer hinds during the mid-luteal phase of the cycle, systemic administration of a luteolytic dose of the prostaglandin F 2α analogue, cloprostenol, caused the concentration of oxytocin in the peripheral circulation to rise. Mean (±SEM) concentrations increased from 8.1 ± 0.7 to 97 ± 8 fmol/ml in red and from 6.2 ± 0.7 to 153 ± 30 fmol/ml in Père David's hinds within 5 min of treatment. During seasonal anoestrus oxytocin secretion in response to cloprostenol was reduced to less than 10% of that during the breeding season, in both species. Cloprostenol treatment raised circulating concentrations of prolactin in both species during the breeding season, and during anoestrus in red deer only. The concentration of oxytocin in a single corpus luteum removed at laparotomy from one red deer hind at the mid-luteal phase of the cycle was 66 nmol/g wet wt; identification was authenticated by HPLC. These results suggest that the corpus luteum secretes oxytocin in the Cervidae, as established previously in the Bovidae, and that luteal oxytocin secretion is stimulated by prostaglandin.

The use of lower doses of the prostaglandin analogue, cloprostenol, for oestrus synchronization in heifers

In an attempt to reduce costs for cattle oestrus synchronization, the use of lower doses (50 and 25% of the conventional dose) of the prostaglandin F 2α analogue, cloprostenol, given by either intramuscular (IM) or intravulvo-submucosal (IVSM) injection, was investigated. There were no differences in the luteolytic response, as measured by either the fall in plasma progesterone or onset of oestrus, between lower cloprostenol doses administered by either method and 500 μg given by IM injection.

Effect of PGF 2α analogue on ovarian oxytocin and progesterone release in heifers: catecholamines are not involved in this process

The assumption that catecholamines are involved in the stimulation of ovarian oxytocin release by PGF 2α is examined in this study. On Day 10 of the oestrus cycle, heifers ( n = 18) were allotted to one of three groups: I, injected with PGF 2α; II, for 15 min before and after injection of PGF 2α, propranolol at a dose of 1.2 μg kg −1 min −1 was infused into the aorta abdominalis ahead of the origin of the ovarian artery, III, for 15 min before and after injection of PGF 2α, heifers were infused with phentolamine (2.5 μg kg −1 body weight min −1). Blood samples were collected frequently from the vena jugularis for 1 h before PGF 2α analogue injection and for 3 h thereafter. The pattern of oxytocin and progesterone release was similar in heifers of all three groups soon after PGF 2α analogue injection; oxytocin piasma concentration rose abruptly from 4 min ( P < 0.01), reached the highest concentration in 6–10 min and thereafter decreased rapidly. Progesterone concentration was elevated concomitantly with oxytocin in Groups I and II ( r = 0.37, P < 0.008 and r = 0.32, P < 0.03, respectively) or followed its surge. We propose that PGF 2α causes the release of oxytocin and temporary elevation of progesterone independently of catecholamines.

Activation of quiescent ovaries by administration of PMSG after LH-RH analogue treatment in heifers

The effect of pregnant mare serum gonadotrophin (PMSG) treatment on activation of quiescent ovaries was examined in heifers. Groups of thirteen, twenty and twelve heifers which showed ovulation within 2 d and corpus luteum (CL) development after injection with a luteinizing hormone releasing hormone analogue (LH-RH-A) were supplementally injected with 500 IU of PMSG (Group I); 500 IU of PMSG and 500 μg of Prostaglandin F 2α analogue (PGF 2α-A; Group II); and 500 μg of PGF 2α-A (Group III) on Day 6 after the injection of 200 μg of LH-RH-A (Day 0), respectively. Estrus appeared in 33.3 to 45.0% of the heifers of the respective groups after the treatment. Ovulation occurred at a significantly (P<0.01) higher rate in Groups I (100%) and II (90.0%) than in Group III (41.7%). The ovarian cyclic activity was initiated in all the heifers that ovulated. Plasma progesterone levels decreased significantly (P<0.05) to about 1 ng/ml on Day 8 and Day 7 in Group I and Groups II and III, respectively. Plasma estradiol-17β (E z) levels increased significantly (P<0.05), reaching a peak on Days 7 to 7.5 in Groups I and II but not in Group III. It is concluded that PMSG treatment stimulates maturation and E z secretion of a follicle, thus promoting ovulation and the onset of ovarian cyclic activity.

Flow and composition of ovarian lymph during pregnancy and luteolysis in the ewe

Ovarian lymph was collected continuously for periods of 65 to 648 h (mean 163 h) from 10 ewes cannulated at stages of pregnancy ranging from 61 to 123 days post coitum. During mid-pregnancy, ovarian lymph flowed with a rhythmic pattern characterized by periods of flow punctuated with short regular intervals of lymph stasis, while later in pregnancy the flow of lymph became more tonic in character. Lymph plasma samples were analyzed for progesterone, pregnenolone, pregnenolone sulphate, androstenedione, testosterone, oestrone, oestrone sulphate and oestradiol-17β. At all stages of pregnancy, luteal ovarian lymph contained high concentrations of progestagens and androgens while the levels of oestrogens in lymph were similar to those reported in blood plasma of pregnant ewes. When serial 10 min samples were collected over an 8-h period from one ewe on day 105 of pregnancy, the concentration and output of progesterone in ovarian lymph varied in a phasic manner, ranging from 3.3 to 7.1 μM and from 17.8 to 58.9 nmol/h, respectively. The intramuscular injection of 50 or 125 μg of the prostaglandin F 2α analogue cloprostenol into six cannulated ewes caused a severe perturbation to the vascular physiology of the luteal ovary. Ovarian lymph flow ceased completely within a few hours after injection (mean interval 4 h) and there was a reduced rate of protein filtration from blood to lymph within the luteal ovary.

Effects of analogues of prostaglandin E 2 and F 2α on the decidual cell reaction in the rat

The identity of the prostaglandins (PGs) involved in the decidual cell reaction is uncertain. In the present study we investigated the ability of analogues of PGE 2 and PGF 2α, 16,16-dimethyl-prostaglandin E 2, methyl ester (16,16Me 2PGE 2) and 15(S)-15-methyl-prostaglandin F 2α (15MePGF 2α) respectively, to bring about decidualization when infused into the uterine lumen of rats sensitized for the decidual cell reaction. As indicated by uterine weights 5 days after the commencement of the infusions into rats in which endogenous PG production had been inhibited by treatment with indomethacin, 16,16Me 2PGE 2 produced decidualization which was equivalent to that produced by PGE 2. By contrast, the infusion of 15MePGF 2α inhibited decidualization, even when PGE 2 was infused concomitantly. As indicated by uterine radioactivity concentrations after i.v. administration of 125I-labeled bovine serum albumin, the PGF 2α analogue also inhibited the endometrial vascular permeability increase which precedes decidualization. Compared to PGE 2, 16,16Me 2PGE 2 was slightly less effective at displacing 3H-PGE 2 from an endometrial membrane preparation; by contrast 15MePGF 2α was considerably less effective. These data suggest that PGE 2 mediates the decidual cell reaction, and that the decidualization obtained in response to PGF 2α may involve its conversion within the uterus to PGE 2.

Correlation of the mating behaviour of bulls with patterns of gonadotrophins and oestrogens in oestrous cows

The correlation between mating behaviour of bulls and patterns of gonadotrophins (GTH, i.e. FSH and LH) and oestradiol-17β (E 2) was examined in oestrous cows, using two bulls. Four cows were placed with each bull in a free stall (10 m × 15 m) at 44 h after the second injection of PGF 2α analogue (cloprostenol). Mating (mounting and ejaculation) behaviour of the bull was observed and serum levels of FSH, LH and E 2 were measured in cows during the next 33 h. The bull ejaculated only with cows in which elevated E 2 levels and a GTH surge occurred. When the time of the GTH peak was designated as 0, and the patterns of hormones in cows with mating behaviour were combined, it was found that 92.3% of ejaculating and 79.1% of mounting behaviour occurred within the range of the GTH surge, indicating that the former behaviour was coincident with the GTH surge.

Superovulation and recovery of zygotes from Nubian and Alpine dairy goats

Thirty-five purebred dairy goats (18 Alpines and 17 Nubians) were subjected to a superovulating hormone program consisting of an 11-d 6α-methyl-17α-acetoxy-progesterone; (MAP; 60 mg) intravaginal sponge treatment; 125 ug i.m. injections of the prostaglandin F 2α analogue cloprostenol on d 1 and 9 of vaginal sponge treatment; and a 3-d, twice-a-day injection of 2.5 mg of pituitary follicle stimulating hormone (FSH-P) i.m. starting at day 9. Vaginal sponges were pulled the morning of day 11 at the time of the fifth FSH-P injection. Of 40 initiated superovulatory cycles, 33 does (10 Alpines and 23 Nubians) responded with an average of 17.7 (range 1 to 29) ovulations. There was no significant difference between the breeds with respect to corpora lutea (CLs) plus follicles ovarian response. A significantly greater (P< 0.05) number of Nubian does were in estrus and mated by 36 h after MAP sponge removal. All does that responded to treatment had done so within 72 h of sponge removal. Of the seven (17.5%) does that showed no estrous response to hormone treatment, six were Alpines (P < 0.01). Six goats (two Alpines and four Nubians) were subjected to a second hormone treatment cycle after a 45-d rest. Five of six does responded to a second hormone treatment cycle with four of five responding with a lower total ovarian response. The interval from sponge removal to mating did not affect the stage or quality of eggs harvested. Rather, the interval from mating to surgical flushing determined the stage of egg development. All animals examined from 24 to 32 h after initial mating had not ovulated. By 50 h, 20 of 22 does had ovulated. A total of 242 ovulated eggs (63%) was harvested, of which 199 (82%) were fertilized. Day 7 flushings yielded 36 eggs (67%), of which 28 (78%) were fertilized. This rate of superovulation, fertilization, and embryo recovery lends credibility to this technique in its ultimate objective of rapidly increasing the number of offspring from superior animals.

Estrus response of indigenous Nigerian Zebu cows after prostaglandin F 2 alpha analogue treatment under continuous observations for two seasons

The study was undertaken to determine the estrus response pattern of Zebu cows indigenous to Nigeria following treatment with prostaglandin F 2α analogue and to determine the effect of season on the estrus parameters. Eighty cyclic Zebu cows were used in both the dry and wet seasons. Two single intramuscular injections of 25 mg of PGF 2α analogue were given per cow 11 days apart regardless of the stage of the estrous cycle. The cows were then observed continuously for 168 h following each injection. The proportion of treated cows responding to PGF 2α treatment in the wet season (90%) was significantly higher (P<0.005) than in the dry season (70.0%). The mean post-injection interval to onset of non-standing estrus (mucus discharge) was 30.6 h and 28.5 h in the dry and wet seasons, respectively. Similarly, the intervals to standing estrus were 69.7 h and 63.9 h in the two seasons, respectively. Seasonal effects were not significant. The duration of non-standing estrus was similar for the two seasons (164.2 h and 162.0 h) while the duration of standing estrus was significantly (P<0.01) longer in the wet season (19.2 h) than in the dry season (12.6 h). Also there was seasonal influence on the body condition score of cows, the palpability of corpora lutea (CL) and the intensity of estrus as determined by the number of mounts (17.9±2.0 and 51.2±3.4 mounts per cow per estrus period in the dry and wet seasons, respectively).

Characterization of the adenylate cyclase of the rat corpus luteum during luteolysis induced by a prostaglandin F 2α analogue

Rats with superluteinized ovaries were injected with the prostaglandin F 2α (PGF 2α) analogue cloprostenol to induce luteolysis. The treatment led to decreased adenylyl cyclase response to hCG and isoproterenol in ovarian homogenates while the response to forskolin remained unchanged indicating that the catalytic unit of the enzyme was not affected by the treatment. The activation of adenylyl cyclase by Mg 2+ or the non-hydrolysable guanosine triphosphate (GTP) analogue guanosine-5′-(β,γ-imido)-triphosphate (GMP-P(NH)P) was not altered by the treatment with cloprostenol. Both basal and hormone-stimulated adenylyl cyclase activity increased with increasing concentration of GMP-P(NH)P. Unstimulated adenylyl cyclase continuously increased with increasing concentrations of Mg 2+. The same applied to forskolin. The dependence of the adenylyl cyclase stimulation by hCG and isoproterenol on Mg 2+ was complex. It is postulated that PGF 2α induces the attenuation of ovarian adenylyl cyclase by a modification in the coupling of the hormone-receptor to the Nβ-component of the adenylyl cyclase complex while the catalytic unit remains unchanged.

Genital tract pressures in mares: II. Changes induced by oxytocin and prostaglandin F 2α

The effects of oxytocin, prostaglandin F 2α and a prostaglandin F 2α analogue on uterine and vaginal pressures in the mare were measured using electronic catheter-tipped pressure transducers. Catheterisation for 70 minutes produced no significant change with time. Oxytocin caused a rapid rise in intrauterine pressure which had subsided 20 minutes later. Cloprostenol (prostaglandin F 2α analogue) caused an increase in uterine pressure which started ten minutes after administration and lasted for the duration of the recording (60 minutes post-injection). Prostaglandin F 2α produced a uterine pressure increase ten minutes after administration which declined over the next 40 minutes. The activity of the three drugs was not consistently affected by reproductive status (oestrus, dioestrus or anoestrus). There were no significant drug effects on intravaginal pressure.

Luteolytic potencin in a novel prostaglandin analogue

Estrus induction in cycling sows with exogenous prostaglandin is hindered by the extended refractory period and resistance of swine to the luteolytic action of PG's. The luteolytic potency of a novel PGF 2α analogue, Schering ZK 71677, was assessed at four different dosages in chronically cannulated cycling swine. Dosages totalling 1, 1.5, 3 and 10 mg of ZK 71677 were split into two injections given intramuscularly on day 13 of the estrous cycle. Onset of behavioural estrus and serum levels of progesterone and PGF metabolite were monitored. The three lowest doses did not advance estrus but did cause a transitory decline in serum progesterone concentration on day 13. The 10 mg level advanced estrus in three of four sows although the overall mean cycle length did not differ from pretreatment cycles (18.5 ± 1.3 vs 21.3 ± 0.6 days). Progesterone values droppd steadily in all four sows in the 10 mg treatment group. No level of ZK 71677 affected serum levels of PGF metabolite. The highest level tested of PGF 2α analogue ZK 71677 elicited an uninterrupted decline in serum progesterone concentrations but was inconsistent in its ability to promote early onset of behavioural estrus in swine.

Secretion of neurophysins by the ovary in sheep

Measurements of venoarterial concentration differences across the ovary in anesthetized sheep have demonstrated that the ovary secretes ovine neurophysin I/II (oNP I/II) and that this process is stimulated by the prostaglandin F 2α analogue, cloprostenol. A parallel increase in the secretion of oxytocin (OT) was observed in response to cloprostenol, and the mean molar ratio of oNP I/II to OT secreted was 1.2. There was no detectable ovarian secretion of oNP III. Secretion of oNP I/II and OT was absent after hysterectomy. The data support other evidence indicating that the corpus luteum synthesizes OT, and confirm that the neurophysin associated with OT in the sheep is oNP I/II.

The effect of “Estrumate” followed by progesterone coils on oestrus synchronization and conception of post-partum beef and dairy cows

To synchronize oestrus, a single dose of 0.5 mg of the prostaglandin F 2α analogue cloprosterol (Estrumate) was administered to 200 post-partum beef and dairy cows. Six, 9 or 13 days following the injection of Estrumate a progesterone-releasing intravaginal device (PRID) was inserted for 12 to 16 days. Among the synchronization treatments investigated, the most promising one was to administer 0.5 mg of Estrumate followed 13 days later by a PRID inserted for 12 days. Following the use of this treatment 87% of post-partum suckling beef and dairy cows manifested oestrus within the first 3 days after PRID removal; 80% appeared in heat between approximately 36 and 72 h following PRID removal. Conception rates for untreated controls, cows inseminated once at 55 h, and cows inseminated twice at 48 and 72 h following PRID removal, were 52, 50 and 48% respectively.

The non-luteolytic effect of prostaglandin F 2α at the beginning of the bovine oestrous cycle: The role of oestrogen?

After the preovulatory gonadotrophin surge, antral follicles ovulate or become atretic; whatever their evolution, they stop secreting oestradiol. Since it was demonstrated that oestrogens were necessary for luteolysis to occur after PGF 2α treatment, their absence could explain the non-luteolytic effect of PGF 2α injected early in the cycle. Thus, cyclic cows received a PGF 2α analogue and oestradiol valerate together on day 3. This treatment did not affect the life span of the corpus luteum. The absence of oestrogens in the blood does not explain the failure of PGF 2α to cause luteolysis in young corpora lutea.

A luteolytic effect of a prostaglandin F 2α analogue in non-pregnant wohen?

Four healthy non-pregnant volunteers with regular cycles were exposed to vaginal suppositories containing a PGF 2α analogue (ICI 81.008, 500–600 μg) twice at 24-hour intervals in the early or mid-luteal phase. In comparison to serum progesterone levels of ovulatory control cycles, this treatment caused a significant decrease of serum progesterone combined with a shortening of the length of the luteal phase by 1.4 days. No gastrointestinal or other adverse effects were noticed during this treatment. Administration of ICI 81.008 in the follicular phase interfered neither with ovulation nor with the length or shape of the following luteal phase. Although limited, these data suggest a luteolytic effect of ICI 81.008 in women.

Specific binding of prostaglandin F 2α to membranes of rat corpora lutea

Prostaglandin F 2α (PGF 2α) binds specifically to a partially purified membrane preparation from rat corpora lutea. The high affinity, low capacity binding component has a K d = 4.7 nM and has a capacity of 0.38 pmol/mg protein. Binding kinetics were temperature-dependent with an association rate constant of 2.5 × 10 5 1/mole-sec and a dissociation rate constant of 4.3 × 10 −4 sec −1 at 22°C. Little competition for binding was shown by other prostaglandins and prostaglandin metabolites; the PGF 2α analogue ICI 81008 (16- m-trifluoromethylphenyl-prostaglandin F 2α) showed a binding affinity similar to that of PGF 2α. The specific binding of PGF 2α to luteal cell membranes was confirmed by electron microscopy using a ferritin-PGF 2α conjugate. Ferritin-PGF 2α, was found predominantly on luteal cell surfaces; little binding occurred on other types of cells present. These data demonstrate specific binding of PGF 2α to rat luteal membranes. It is suggested that the luteolytic action of PGF 2α in the rat may be receptor-mediated.