Prostaglandin production by the early pregnant guinea-pig uterus in relation to implantation and luteal maintenance, and the effect of oestradiol

The outputs of prostaglandin (PG) F-2 alpha and PGE-2, but not of 6-oxo-PGF-1 alpha, from the guinea-pig uterus were significantly lower on Days 7 and 15 of pregnancy than on the corresponding days of the cycle. Uterine PGF-2 alpha output increased 28-fold between Days 7 and 15 of the cycle but only 4- to 5-fold between these same days of pregnancy. Uterine PGE-2 and 6-oxo-PGF-1 alpha outputs increased 2- to 3-fold between Days 7 and 15 of the cycle and of pregnancy. Endometrial PGF-2 alpha synthesizing capacity was 60-70% lower on Days 7 and 15 of pregnancy than on the corresponding days of the cycle, although it increased 2-fold and 2.5-fold between these days of pregnancy and of the cycle, respectively. Endometrial PGE-2 and 6-oxo-PGF-1 alpha synthesizing capacities showed no significant variation amongst Days 7 and 15 of the cycle and of pregnancy, except that endometrial PGE-2 synthesizing capacity was lower on Day 7 of the cycle. Oestradiol treatment (10 micrograms s.c. daily from Days 10 to 14 of pregnancy) did not affect plasma progesterone concentrations, uterine 6-oxo-PGF-1 alpha output, and endometrial PGF-2 alpha, PGE-2 and 6-oxo-PGF-1 alpha synthesizing capacities in 9/12 guinea-pigs when examined on Day 15. Uterine PGF-2 alpha and PGE-2 outputs increased 3- and 1.5-fold, respectively, in these guinea-pigs, but were still much lower than the outputs from the Day-15 non-pregnant uterus. The pregnancies appeared unaffected in these oestradiol-treated guinea-pigs. In the other 3 oestradiol-treated animals, uterine PGF-2 alpha output was 20- to 30-fold higher than in untreated, pregnant guinea-pigs on Day 15, and 2- to 3-fold higher than in Day-15 non-pregnant guinea-pigs. Uterine PGE-2 and 6-oxo-PGF-1 alpha outputs also tended to be higher in these treated guinea-pigs. In these 3 guinea-pigs, endometrial PGF-2 alpha, PGE-2 and 6-oxo-PGF-1 alpha synthesizing capacities were 4.0-, 3.4- and 2.5-fold higher, respectively, than in untreated, pregnant guinea-pigs on Day 15, and tended to be higher than in Day-15 non-pregnant guinea-pigs. Plasma progesterone concentrations were much lower in these 3 animals than in the other 9 treated with oestradiol, and also much lower than in untreated, pregnant guinea-pigs on Day 15.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prostaglandin F-2 alpha is transferred from the uterus to the ovary in the sheep by lymphatic and blood vascular pathways

[3H]Prostaglandin F-2 alpha (PGF-2 alpha) was infused into a uterine lymphatic vessel or a uterine vein for up to 1 h, or injected into the uterine lumen of anaesthetized non-pregnant sheep 7-15 days after oestrus. After an intraluminal injection, labelled PGF-2 alpha was recovered in uterine lymph and peak radioactivity was reached 50 min after injection. [3H]PGF-2 alpha infused at a constant rate into a uterine lymphatic vessel resulted in a maximum concentration of radioactivity in plasma which was 5.6- and 1.7-fold higher in the adjacent utero-ovarian and ovarian vein, respectively, than in carotid arterial plasma. Estimation of the amount of infusate transferred from a lymphatic into ovarian venous blood gave a value (0.4%) similar to that for transfer from a uterine vein (0.3%). Evidence for local transfer was substantiated by the presence of significantly higher concentrations of 3H-labelled compounds in the ovary and corpus luteum adjacent to the site of intra-lymphatic infusion compared with those in the opposite organs. The concentrations in the adjacent ovary and corpus luteum were significantly greater when an intra-lymphatic rather than intra-uterine vein infusion was adopted. The results show that [3H]PGF-2 alpha is transferred locally from uterine lymphatic vessels into the adjacent ovary, corpus luteum and ovarian vein.     

Modification of prostaglandin F-2 alpha synthesis and release in the ewe during the initial establishment of pregnancy

Pregnant (N = 10) and non-pregnant (N = 10) ewes were bled every 2 h from Days 12 to 17 after oestrus (oestrus = Day 0). Plasma concentrations of progesterone, 15-keto-13,14-dihydro-PGF-2 alpha and 11-ketotetranor-PGF metabolites were determined in all samples. The number of PGF-2 alpha pulses in non-pregnant ewes was 8.2 +/- 0.4 (mean +/- s.e.m.) with an interpulse interval of 10.7 +/- 0.7 h. Two or 3 pulses of low frequency (interpulse interval = 13.4 +/- 1.6 h) occurred in most non-pregnant ewes before the onset of luteolysis; the interpulse interval then decreased to 7.9 +/- 0.4 h for the 6.0 +/- 0.3 pulses temporally associated with luteolysis. In contrast, the number of PGF-2 alpha pulses in pregnant ewes was lower (2.5 +/- 0.7, 0-8) and the interpulse intervals longer (18.9 +/- 6.1 h). Most pulses occurred on Days 14 and 15 in the pregnant and non-pregnant ewes. The mean concentrations of both PGF-2 alpha metabolites in non-pregnant ewes were highest on Day 15 while basal levels of both metabolites remained constant at all times. In pregnant ewes, the mean concentrations of both metabolites were highest on Day 14; basal concentrations of both metabolites were also highest on Day 14. The mean concentrations of 15-keto-13,14-dihydro-PGF-2 alpha were higher in pregnant than in non-pregnant ewes on Days 13 and 14 (P less than 0.05) and higher in non-pregnant than pregnant ewes on Day 15 (P less than 0.05). The basal concentrations of the 15-keto metabolite were higher in pregnant than non-pregnant ewes at Days 13, 14, 15, 16 and 17 (P less than 0.05). Both the mean and the basal concentrations of 11-ketotetranor-PGF metabolites were higher in pregnant than in non-pregnant ewes on Day 14 (P less than 0.05). It is concluded that uterine production of PGF-2 alpha peaks at Days 14-15 after oestrus in pregnant and non-pregnant ewes. Patterns of release differ, however, in that non-pregnant ewes have a pulsatile PGF-2 alpha pattern superimposed on a constant baseline, while pregnant ewes have an increasing basal secretory pattern which is more nearly continuous, i.e. not pulsatile in form. Modification of pulsatile PGF-2 alpha synthesis and release is therefore a key aspect of prolongation of luteal function at the beginning of pregnancy in the ewe.     

Evidence for a systemic role for ovarian oxytocin in luteal regression in sheep

Jugular venous concentrations of oxytocin and progesterone changed in parallel during the oestrous cycle in the ewe, falling at luteal regression and rising with formation of the new corpus luteum. These fluctuations in the circulating concentration of oxytocin were not caused by changes in its metabolic clearance rate. On Days 6-9 of the cycle circulating oxytocin concentrations exhibited a diurnal rhythm, peaking at 09:00 h; this rhythm was absent on Days 11-14. Although there was no evidence for increased production of oxytocin at or preceding luteal regression in samples taken daily, more frequent sampling revealed that two thirds of detected surges of uterine secretion of prostaglandin (PG) F-2 alpha were accompanied by raised levels of oxytocin. This oxytocin was not of pituitary origin. Luteal regression induced with cloprostenol on Day 8 after oestrus caused a decrease in circulating progesterone level followed after 24 h by a fall in oxytocin. Measurements of oxytocin in the ovary and other organs before and after treatment with cloprostenol identified the corpora lutea as a major potential source of oxytocin, and suggested that 98% of luteal oxytocin was available for secretion in response to prostaglandin stimulation. The data are consistent with a role for ovarian secretion of oxytocin in response to uterine release of PGF-2 alpha in the control of luteal regression.     

Continuous infusion of oxytocin prevents induction of uterine oxytocin receptor and blocks luteal regression in cyclic ewes

Continuous intravenous infusion of oxytocin (3 micrograms/h) between Days 13 and 21 after oestrus delayed return to oestrus by 7 days (length of cycle 23.3 +/- 0.6 days compared to 16.6 +/- 0.2 days in control ewes). At a lower infusion rate (0.3 micrograms/h) oxytocin delayed luteolysis in only 2 of 5 ewes. Treatment from Day 14, when luteolysis had already begun, was ineffective. Delay of luteal regression by oxytocin had no effect on the length of subsequent cycles. Measurement of circulating progesterone concentrations and luteal weight showed that prolongation of the oestrous cycle was due to prevention of luteal regression. Luteal regression and behavioural oestrus were induced during continuous oxytocin administration begun on Day 13 when cloprostenol was given on Day 15 (mean cycle length, 17.3 +/- 0.21 days). Continuous oxytocin infusion from Day 13 blocked the rise in uterine oxytocin receptor concentrations which normally precedes oestrus. Mean receptor concentrations in caruncular and intercaruncular endometrium and in myometrium were 76, 36 and 9 fmol/mg protein on Day 17 in ewes receiving continuous oxytocin (3 micrograms/h); in control ewes these values were 675, 638 and 130 fmol/mg protein respectively at oestrus. Receptor concentrations on the day of oestrus in ewes receiving oxytocin and cloprostenol were not significantly different from those in control ewes (649, 852, and 109 fmol/mg protein respectively). Since cloprostenol, a PGF-2 alpha analogue, overcame the antiluteolytic action of oxytocin, it is suggested that continuous oxytocin treatment may inhibit uterine production of PGF-2 alpha, possibly by down regulating the uterine oxytocin receptor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of systemic intravenous infusion of PGF-2 alpha and 13,14-dihydro-15-keto-PGF-2 alpha on the release of oxytocin-associated neurophysin from the ovary in the ewe

Systemic intravenous infusion of physiological concentrations of PGF-2 alpha and its major metabolite, 13, 14-dihydro-15-keto-PGF-2 alpha (PGFM) into non-pregnant ewes possessing a corpus luteum induced the release of oxytocin-neurophysin. These results suggest that, during luteolysis, endogenous release of uterine PGF-2 alpha would be able to stimulate the release of ovarian oxytocin and oxytocin-neurophysin from the ovary.     

Interrelationships between progesterone, 13,14-dihydro-15-keto PGF-2 alpha (PGFM) and LH in cyclic and early pregnant cows

Plasma progesterone and LH secretion patterns were examined in 18 mature dairy cows during the oestrous cycle and after insemination. Blood samples were collected every 15 min for 8 h per day on Days 3, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 18, 19, 20 and 21 of the oestrous cycle, then, in the same cows, at the same times during early pregnancy. PGF-2 alpha secretion rates (as determined by plasma PGFM concentrations) were also monitored on Days 14, 16 and the day of, or equivalent to, luteal regression. Mean daily plasma progesterone concentrations were similar until Day 16 in cyclic and pregnant cows, after which values in non-pregnant animals declined. Regression analysis indicated that progesterone concentrations were best described by a quadratic expression with fitted maximum values on Day 13 in non-pregnant animals but values increased linearly over the whole period to Day 21 in pregnant cows. The frequency, amplitude and area under the curve of LH episodes showed no significant differences between cyclic and pregnant animals. In pregnant cows, the amplitude and area under the curve of progesterone episodes increased linearly between Days 8 and 21, although no such increase occurred in cyclic cows. Low-level PGFM episodes were present in cyclic and pregnant cows on Days 14 and 16 after oestrus, and high amplitude episodes occurred in non-pregnant cows during luteal regression. Pregnant cows showed a significant depression of the amplitude, but not the frequency of episodes at the expected time of luteal regression. These results confirm that the corpus luteum of pregnancy secretes an increasing amount of progesterone per se and per unit of LH until at least Day 21 after mating. They further suggest that the corpus luteum of the cyclic cow may experience small episodes of PGF-2 alpha and be subjected to initial degenerative changes by Day 14 after oestrus, some time before the onset of definitive luteolysis.     

Effect of infusion of PGI-2, 6-keto-PGF-1 alpha and PGF-2 alpha on luteal function in the pregnant rat

Prostacyclin (PGI-2), 6-keto-PGF-1 alpha and PGF-2 alpha were infused continuously for 6 h into the dorsal aorta of rats 8 days pregnant. PGF-2 alpha (10 micrograms/h) significantly reduced plasma progesterone concentrations by 66% and luteal tissue concentrations of pregnenolone and progesterone by 78% and 95% respectively. Plasma concentrations of 20 alpha-dihydroprogesterone remained unchanged whilst luteal tissue concentrations rose 2-fold. Plasma progesterone concentrations were significantly reduced to 50% by PGI-2 (10 micrograms/h) but were unaffected by 6-keto-PGF-1 alpha (10 or 100 micrograms/h). Neither PGI-2 (10 micrograms/h) nor 6-keto PGF-1 alpha (10 or 100 micrograms/h) had any significant effect on plasma concentrations of 20 alpha-dihydroprogesterone or on luteal tissue concentrations of pregnenolone, progesterone or 20 alpha-dihydroprogesterone. Arterial blood pressure was unaffected by PGF-2 alpha and 6-keto-PGF-1 alpha, but was significantly reduced by PGI-2 at infusion rates greater than or equal to 60 micrograms/h.     

Effect of betamethasone treatment on luteal lifespan and the LH response to GnRH in dairy cows

Betamethasone (a synthetic glucocorticoid, 15 mg) was administered i.m. twice daily for 10 days to 4 regularly cycling dairy cows, beginning on Day 10 of the oestrous cycle. Luteal function, monitored by plasma progesterone, was extended by 7, 9, 19 and 20 days, respectively. Luteal function in the next cycle was normal. Endogenous cortisol values were suppressed for 14, 13, 34 and 27 days, respectively. Pituitary responsiveness to 20 micrograms GnRH was assessed by LH measurement on Days -1, +3 and +7 relative to the start of betamethasone treatment. There was a progressive decrease in peak LH concentrations after each GnRH challenge compared to control cows. Hourly measurements of PGF-2 alpha metabolite during the expected period of luteolysis failed to reveal normal increases. It is suggested that betamethasone caused prolonged luteal function, either by directly inhibiting PGF-2 alpha release, or by suppressing pituitary stimulation of follicular growth and hence lowering oestradiol concentrations, since it is known that PGF-2 alpha and oestradiol act synergistically to cause luteolysis.     

Relationship of oestrus synchronization method, circulating hormones, luteinizing hormone and prostaglandin F-2 alpha receptors and luteal progesterone concentration to premature luteal regression in superovulated sheep

Ewes were treated with exogenous follicle-stimulating hormone (FSH) and oestrus was synchronized using either a dual prostaglandin F-2 alpha (PGF-2 alpha) injection regimen or pessaries impregnated with medroxy progesterone acetate (MAP). Natural cycling ewes served as controls. After oestrus or AI (Day 0), corpora lutea (CL) were enucleated surgically from the left and right ovaries on Days 3 and 6, respectively. The incidence of premature luteolysis was related (P less than 0.05) to PGF-2 alpha treatment and occurred in 7 of 8 ewes compared with 0 of 4 controls and 1 of 8 MAP-exposed females. Sheep with regressing CL had lower circulating and intraluteal progesterone concentrations and fewer total and small dissociated luteal cells on Day 3 than gonadotrophin-treated counterparts with normal CL. Progesterone concentration in the serum and luteal tissue was higher (P less than 0.05) in gonadotrophin-treated ewes with normal CL than in the controls; but luteinizing hormone (LH) receptors/cell were not different on Days 3 and 6. There were no apparent differences in the temporal patterns of circulating oestradiol-17 beta, FSH and LH. High progesterone in gonadotrophin-treated ewes with normal CL coincided with an increase in total luteal mass and numbers of cells, which were primarily reflected in more small luteal cells than in control ewes. Gonadotrophin-treated ewes with regressing CL on Day 3 tended (P less than 0.10) to have fewer small luteal cells and fewer (P less than 0.05) low-affinity PGF-2 alpha binding sites than sheep with normal CL. By Day 6, luteal integrity and cell viability was absent in ewes with prematurely regressed CL. These data demonstrate that (i) the incidence of premature luteal regression is highly correlated with the use of PGF-2 alpha; (ii) this abnormal luteal tissue is functionally competent for 2-3 days after ovulation, but deteriorates rapidly thereafter and (iii) luteal-dysfunctioning ewes experience a reduction in numbers of small luteal cells without a significant change in luteal mass by Day 3 and, overall, have fewer low-affinity PGF-2 alpha binding sites.     

Involvement of gonadotropins in induction of luteolysis in pigs

In our previous study we have demonstrated that treatment of endometrial explants with LH increased 13,14-dihydro-15-ketoprostaglandin F(2alpha) (PGFM) accumulation in pigs. This was particularly visible on Days 14-16 of the estrous cycle. Action of gonadotropin in porcine endometrium appears to be mediated by LH/hCG receptors whose number is dependent on the day of the estrous cycle. In the current study i.v. infusion (1 hour) of hCG (200 IU) performed on Days 10 (n=4) and 12-14 (n=4) of the porcine estrous cycle did not affect plasma PGFM (ng/ml+/-SEM) concentrations. In contrast, administration of hCG on Days 15-17 produced, depending on plasma PGFM level before the infusion period, three different types of response: I. plasma PGFM surge of amplitude 0.62+/-0.15 was observed when the mean basal pre-infusion PGFM plasma level was 0.23+/-0.05 (n=6 gilts); II. the delayed PGFM surge of amplitude 0.62+/-0.15 was determined when basal pre-infusion PGFM level was 0.80+/-0.20 (n=6); and III. lack of PGFM response to hCG was found when basal pre-infusion PGFM level was 1.09+/-0.61 (n=6). Concentrations of plasma PGFM before and after saline infusion did not differ on Days 12-14 and 16 of the estrous cycle. In the next experiment blood samples were collected every 1 hour on Days 12-19 of the estrous cycle to determine concentrations of LH, PGFM and progesterone in four gilts. In particular gilts, plasma peaks of LH closely preceded surges of PGFM in 72.7, 84.6, 75.0 and 66.6 percent, respectively. The highest PGFM surges followed a decline in plasma progesterone concentration. We conclude that the increased PGF(2alpha) metabolite production after hCG infusion during the late luteal phase of the estrous cycle as well as the relationship between plasma LH and PGFM peaks suggest the LH involvement in the elevation of endometrial PGF(2alpha) secretion in pigs, and, in consequence, induction of luteolysis.     

Effects of synchronization and frequency in insemination on fertility.

Fifty-four normally cycling, non-lactating mares were given 2 injections (i.m.) of PGF-2 alpha (10 mg) 14 days apart without regard to stage of the oestrous cycle. At 19 days after the first PGF-2 alpha treatment, a single i.m. injection of either hCG (3300 i.u.) or a GnRH-analogue (500 micrograms) was administered. Each mare was inseminated with 100 X 10(6) motile spermatozoa at one of the following frequencies: once only on Day 20; every other day during oestrus or at least on Days 19 and 21; or daily during oestrus or at least on Days 19, 20, 21 and 22. Eighteen control mares received saline injections on Days 0 and 14, and were inseminated either on the 4th day of oestrus or every other day or daily beginning on the 2nd day of oestrus. More (P greater than 0.05) PGF-2 alpha treated mares displayed their 1st day of oestrus on Days 14 to 20 than control mares (80.6 versus 27.8%). During cycle 1, fewer (P greater than 0.05) treated mares became pregnant compared to controls; 38.9, 25.0 and 66.7% for PGF-2 alpha + hCG, PGF-2 alpha + GnRH-A and control mares, respectively. After three cycles, the pregnancy rates for mares inseminated every other day or daily were higher (P less than 0.05) than mares inseminated only once during oestrus (88.9 and 88.2 versus 64.7%).     

Change in responsiveness of rabbit corpus luteum to prostaglandin F-2 alpha during pregnancy and pseudopregnancy.

Previous studies have suggested that prostaglandin F-2 alpha (PGF-2 alpha) may have a role in luteolysis in rabbits. Rabbits (4-6/group) were given a single injection of saline, or 100, 500 or 2500 micrograms PGF-2 alpha (i.m.) on Day 7, 9, 12 or 15 of pregnancy or pseudopregnancy. Daily blood samples were taken via the marginal ear vein before and for 3 days after the PGF-2 alpha injection. Concentrations of serum progesterone were determined by radioimmunoassay in pseudopregnant rabbits. There were no significant differences between PGF-2 alpha-treated and control rabbits on Days 7 or 9. On Day 12 of pseudopregnancy, progesterone concentration was significantly (P less than 0.05) lower in treated than in control rabbits, the effect being dose dependent. On Day 15 of pseudopregnancy, it was not possible to distinguish between controls and treated groups because luteolysis occurred in all rabbits. In contrast, on Days 7 and 9 of pregnancy, the concentration of progesterone in treated groups was lower than in the control groups (P less than 0.05), the effect being dose dependent. This difference was maintained throughout the sampling period and resulted in termination of pregnancy. By Day 12 of pregnancy, the response to PGF-2 alpha was transient, with a significant decline in progesterone for only 2 days, followed by a return to control concentrations and normal delivery of litters. On Day 15 of pregnancy, no treatment with PGF-2 alpha significantly altered progesterone concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changing responsiveness of luteal cells of the marmoset monkey (Callithrix jacchus) to luteotrophic and luteolytic agents during normal and conception cycles

Dispersed marmoset luteal cells were incubated for 2 h and progesterone production measured after exposure to hCG, cloprostenol, dibutyryl cAMP, PGF-2 alpha, PGF-2, adrenaline or melatonin. The cells were studied on Days 6, 14 and 20 after ovulation in conception and non-conception cycles. Luteal cells from Day 14 non-pregnant marmosets were compared with human luteal cells taken in the mid-luteal phase. All the treatments stimulated progesterone production including cloprostenol, which is luteolytic when administered to the marmoset in vivo, but the degree of response varied with the stage of the cycle or pregnancy and between marmoset and human luteal cells. In the marmoset, overall analysis of the effect of the treatments showed that, on Day 6 after ovulation, there was no significant effect of any of the treatments in cells from pregnant or non-pregnant animals. In contrast, luteal cells from non-pregnant animals on Day 14 showed a significant response to the treatments (F (8,41) = 2.79, P less than 0.0145) whereas cells from pregnant Day-14 animals were responsive; in cells from pregnant animals, the control production of progesterone was high and already equivalent to the levels stimulated by the treatments. By Day 20, cells from pregnant animals produced lower control concentrations of progesterone than did those on Day 14 and there was a significant overall effect of the treatments (F (8,33) = 3.78, P less than 0.003). These results show that the marmoset CL gains responsiveness to treatment between Days 6 and 14 after ovulation in the non-pregnant cycle. In pregnancy, on Day 14, 2 days after attachment of the embryo, the high control concentrations of progesterone and absence of response to treatment suggest that an embryo message may have affected the CL, providing an endogenous stimulus.     

Studies on prostaglandin metabolism in corpora lutea of rabbits during pregnancy and pseudopregnancy

Corpora lutea and ovarian stromal tissue were analysed for prostaglandin (PG) concentrations and activities of enzymes involved in PG metabolism at 8, 10, 12, 13 and 15 days after induction of ovulation. In CL of pseudopregnant rabbits, the PGE-2-9-ketoreductase (PGE-2-9-KR) was highly active on Days 10, 12 and 15 when compared with Day 8 (P less than 0.01; P less than 0.001; P less than 0.05). In pregnant animals PGE-2-9-KR activity was only increased on Day 12 (P less than 0.05) but declined to basal levels on Days 13 and 15. Comparing PGE-2-9-KR activity of pseudopregnant and pregnant animals, a significant elevation was found on Day 15 of pseudopregnancy (P less than 0.025). Activities of PG-15-hydroxydehydrogenase did not exhibit any significant changes with time in pseudopregnant or pregnant rabbits. PGE-2 concentrations were increased on Days 12, 13 and 15 (P less than 0.025) when compared with Day 8. Changes in PGF-2 alpha concentrations paralleled those of PGE-2-9-KR. The concentrations of PG metabolites 13,14-dihydro-15-keto-PGE-2 and -PGF-2 alpha were lower than those of the primary PGs and did not show stage-specific changes in pseudopregnant and pregnant animals. These results demonstrate that the rabbit CL possesses enzymes to convert PGE-2 to PGF-2 alpha and to metabolize both PGs. PGE-2-9-KR may be involved in regulating the PGF-2 alpha/PGE-2 ratio and possibly in controlling the life-span of the corpus luteum.     

Prostaglandin output from the early pregnant rat uterus superfused in vitro, and the effect of A23187 and trifluoperazine

The outputs of prostaglandin (PG) E-2 and 6-oxo-PGF-1 alpha from the early pregnant rat uterus superfused in vitro were significantly higher (P less than 0.05) on Day 4 (09:00-10:00 h) and Day 5 (14:00-15:00 h) than on Day 2 (09:00-10:00 h) and Day 5 (14:00-15:00 h). PGF-2 alpha output was significantly higher (P less than 0.05) only on Day 5 (09:00-10:00 h). PGE-2 was the major PG released at all times, although the amounts of PGF-2 alpha and/or 6-oxo-PGF-1 alpha released were often only slightly less. These findings are consistent with uterine PGs having a role in implantation in the rat. A23187 stimulated 6-oxo-PGF-1 alpha output and, except on Day 4 (09:00-10:00 h), PGF-2 alpha output at all times studied. A23187 had little effect on PGE-2 output. The greatest stimulatory effect of A23187 on 6-oxo-PGF-1 alpha and PGF-2 alpha outputs occurred on Day 5 (09:00-10:00 h), which is the day of highest uterine PGH-2 synthetase activity. These increases in response to A23187 were prevented by trifluoperazine (100 microM), a calmodulin antagonist. Trifluoperazine had no inhibitory effect on the high basal output of PGs on Day 5 (09:00-10:00 h), but caused a small increase in uterine PG output.     

Release of prostaglandin F-2 alpha and the timing of events associated with luteolysis in ewes with oestrous cycles of different lengths

Ewes (N = 32) were bled every 2 h from 5 days before expected oestrus until the end of oestrus. Plasma concentrations were determined for progesterone to monitor luteal activity and for the prostaglandin F-2 alpha (PGF-2 alpha) metabolites, 15-keto-13,14-dihydro-PGF-2 alpha and 11-ketotetranor-PGF to determine uterine synthesis and release of PGF-2 alpha. Most of the variation in cycle length was associated with the time of onset of luteolysis, the timing of events after luteolysis being constant and not related to cycle length. The time of occurrence of the first PGF-2 alpha pulse and the interval between this pulse and the start of luteolysis were the two main determinants responsible for oestrous cycle length. Several PGF-2 alpha pulses with interpulse intervals of 15.9 h occurred before the onset of functional luteolysis compared with 7.7 h for pulses associated with luteolysis. The numbers of PGF-2 alpha pulses and interpulse intervals were similar for oestrous cycles of different lengths. While a gradual decline in progesterone concentrations was observed before functional luteolysis in the ewes with longer cycles, this did not appear to be an integral part of the stimulus which initiates the pulse frequency of PGF-2 alpha required for luteolysis. We therefore suggest that differences in oestrous cycle length in the ewe are determined by the time of the onset of PGF-2 alpha pulsatile release, and especially by the time of increased pulse frequency.     

Prostaglandin F-2 alpha causes regression of an hCG-induced corpus luteum before day 5 of its lifespan in cattle

The experimental objective was to evaluate how a spontaneously formed corpus luteum (CL) differed in its response to prostaglandin (PG) F-2 alpha, given during the first 5 days after ovulation, from a CL induced during dioestrus with hCG. Sixteen Holstein heifers were used during each of 2 consecutive oestrous cycles. During the first cycle (sham cycle), heifers were given no PGF-2 alpha (control) or PGF-2 alpha (25 mg, i.m.) on Day 2, 4 or 6 (oestrus = Day 0). During the second cycle (hCG-treated cycle), heifers were given hCG (5000 i.u., i.m.) on Day 10, followed by no PGF-2 alpha (control) or PGF-2 alpha on Day 12, 14 or 16, corresponding to 2, 4 or 6 days after the ovulatory dose of hCG. A new ovulation was induced in 13 of 16 heifers given hCG on Day 10. Luteolysis did not occur immediately in heifers given PGF-2 alpha on Day 2 or 4 during the sham cycle, but concentration of progesterone in serum during the remainder of the cycle was lower in heifers given PGF-2 alpha on Day 4 than in sham controls or heifers given PGF-2 alpha on Day 2 (P less than 0.05). Luteolysis occurred immediately in heifers given PGF-2 alpha on Day 6 of the sham cycle or on Day 12, 14 or 16 of the hCG-treated cycle, with concentration of progesterone in serum decreasing to less than 1 ng/ml within 2 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of prostaglandin F-2 alpha release and delay of luteolysis after active immunization against oxytocin in the goat

Active immunization against oxytocin significantly prolonged the oestrous cycle in 3 out of 4 goats; the mean (+/- s.e.m.) cycle length was 29.1 +/- 1.7 days (n = 12) compared to 19.4 +/- 0.6 days (n = 9) in control animals. During Days 10-21 of the cycle in the 3 responsive goats, peripheral plasma concentrations of progesterone and oxytocin were steady and those of 13,14-dihydro-15-keto-prostaglandin F-2 alpha were very low (50-100 pg X ml-1) with no marked pulsatile activity. The major effect of immunization would appear to be suppression of the synthesis of the uterine luteolysin PGF-2 alpha, thus confirming that endogenous oxytocin has a facilitatory role in luteolysis via prostaglandin production.     

Effects of progestagen treatment on concentrations of prostaglandins and oxytocin in plasma from the posterior vena cava of post-partum beef cows

The role of PGF-2 alpha in determining the lifespan of corpora lutea in the post-partum beef cow was investigated. In control cows (N = 5) induced to ovulate at Day 28 to 36 post partum by injection of 1000 i.u. hCG, corpora lutea had an average lifespan of only 8 days. In cows pretreated with 6 mg implants of a progestagen (norgestomet, N = 4) for 9 days, with implant removal 2 days before injection of hCG, luteal lifespan averaged 17.5 days. Concentrations of PGF-2 alpha in 9 hourly samples of plasma collected from the posterior vena cava via indwelling catheters were higher on Days 4 through 9 after injection of hCG (P less than 0.05) in the cows with short-lived corpora lutea. Greater release of PGF-2 alpha could therefore be a major factor in premature luteal regression. Concentrations of PGFM and oxytocin did not differ between cows with corpora lutea of short or normal lifespan. In a second experiment, concentrations of PGF-2 alpha in plasma from the posterior vena cava were examined during treatment with norgestomet (N = 8) or in contemporary controls (N = 7). In progestagen-treated cows, PGF-2 alpha was higher than in control cows (P less than 0.05), beginning on Day 3 of treatment and peaking on Day 5. It is concluded that the post-partum uterus increases secretion of PGF-2 alpha very early after first exposure to endogenous or exogenous progestagen.