Effect of intrauterine iodine infusion on luteal function and blood PGF2a concentration in cycling goats

Studies were conducted to determine the effect of iodine infusion on the luteal function of goats, as evident by blood progesterone concentration, and on plasma PGF2a levels. Ten cycling mixed breed goats were synchronized for estrus by PGF2a (5 mg) and given a single intrauterine iodine infusion on day 5 and on day 15 of the estrous cycle. Iodine infusion on day 5 (group II) resulted in shorter estrous length (8.2 days) and a 7-fold increase in plasma PGF2a concentration as compared to control animals (group I) given distilled water infusion. Similar infusion on day 15 (group III), on the other hand, failed to alter the estrous cycle length but induced a moderate increase in PGF2a concentration which lasted only for a brief period. The progesterone levels declined concomitantly as PGF2a levels rose after iodine infusion in group II animals but failed to decline until after 24 hours in group III animals. The studies indicate that the endometrium reacts to the chemical stimuli and releases PGF2a which, in turn, alters the luteal function.     

Corpus luteum function in the ewe: Effect of PGF2α and prostaglandin synthetase inhibitors

A series of experiments were conducted to evaluate the effects of mode and frequency of administration and estrous cycle stage on the response of the cycling ewe to PGF_2α. The effects of dexamethasone, arachadonic acid and prostaglandin synthetase inhibitors on estrous cycle length and plasma progesterone levels were also determined.Intramuscular administration of 5 or 10 mg of PGF_2α, on days 8 and 9 after estrus (5 ewes/group), significantly (p<.01) shortened the mean length of the estrous cycle and the interval from the end of treatment to estrus. Mean plasma progesterone levels, 24 hours after initial injection, were significantly (p<.01) lowered. When administered on day 8 only, these doses were considerably less effective in shortening estrous cycle length or lowering plasma progesterone levels. Intravaginal administration of PGF_2α, by polyurethane tampon, was also largely ineffective.Treatment of ewes with 10 mg of PGF_2α i.m., on days 3 and 4 of the estrous cycle, resulted in a return to estrus in 2 days in 25% of the treated animals. Plasma progesterone levels of PGF_2α-treated ewes were significantly lower than controls on the second, third and fourth days after the start of dosing. It would appear that PGF_2α exerts a retarding effect on developing CL functionality.The prostaglandin synthetase inhibitors, aspirin, flufenamic acid and 1-p-chlorobenzylidene-2-methyl-5-methoxy-3-indenylacetic acid, were administered orally or parenterally for 16 days beginning on day 8 of the estrous cycle. These compounds failed to prolong estrous cycle length. Parenteral administration of dexamethasone did not result in PGF_2α release in the cycling ewe, at least not in quantities sufficient to induce luteolysis. The prostaglandin precursor, arachadonic acid, also was not luteolytic when given parenterally to cycling ewes.     

Corpus luteum function in the guinea pig: effect of pgf2 alpha and inhibitors of prostaglandin and progesterone biosynthesis.

Exogenous PGF_2α failed to consistently alter estrous cycle length of the guinea pig. A wide range of dose levels were administered with varying frequency, at different stages of the estrous cycle, in different vehicles and by various routes. Massive doses of PGF_2α (5.0–10.0 mg) produced a significant (p<.05), although transient, lowering of plasma progesterone levels. Smaller doses were ineffectual. An i.p. injection of 25 mg of PGF_2α was toxic in four of five treated animals. It would appear that the intact guinea pig is extremely resistant to the luteolytic effects of parenterally administered PGF_2α.Estradiol-17β, administered s.c. on days 3 to 10 of the estrous cycle, significantly (p<.05) reduced corpus luteum diameter and plasma progesterone levels. Estrous cycle length was unaffected. Clomiphene, in the same experiment, caused premature vaginal opening in some treated animals, but corpus luteum size and plasma progesterone levels were unaffected and no ovulations occurred.The prolactin secretion inhibitor, CB-154, administered early in the estrous cycle, did not have any effect on estrous cycle length of the guinea pig alone or in combination with PGF_2α. The prostaglandin precursor, arachidonic acid, also failed to influence estrous cycle length when administered on days 8 and 9 of the cycle. Plasma progesterone levels remained unaltered.Oral administration of a prostaglandin synthetase inhibitor, (MK-715), caused a small, but non-significant (p>.05) prolongation of the estrous cycle. The progesterone biosynthesis inhibitors, aminoglutethimide and 6β-hydroxy-3α, 5α-cyclo-androstane-17-one did not effect estrous cycle length or plasma progesterone levels of the guinea pig.     

Progesterone and 15-Keto-13,14-Dihydroprostaglandin F2α Levels in Peripheral Circulation After Intrauterine Iodine Infusions in Cows

The effect of intrauterine iodine infusion on estrous cycle length was studied in four cows. The infusions were performed at various times of the estrous cycle: early, middle, late, and during luteolysis. Blood samples were drawn every third hour from the jugular vein. Progesterone and 15-keto-13,14-dihydroprostaglandin F2α (the main metabolite of PGF2α) were measured to monitor luteal activity and prostaglandin release. No release of prostaglandins was observed immediately following intrauterine infusion. Infusion in two cows on day 5 of the estrous cycle resulted in prostaglandin release after 54 and 69 hrs., respectively, followed by luteal regression and the occurrence of estrus at approx. five days after infusion. Infusions performed on days 11 or 12 resulted in prostaglandin release after 147 and 120 hrs., respectively, followed by luteolysis and heat after a 19 day estrous cycle. Infusion in two cows at days 16 and 17 resulted in prostaglandin release after 117 hrs. in both animals. One cycle was prolonged whereas the other cycle was normal in duration. One cow infused on day 20 following the occurrence of the first prostaglandin surge had a cycle length of 26 days, whereas another cow infused on day 20 was not affected because luteolysis was essentially complete by the time of infusion. One animal infused on day 5 did not respond to the iodine infusion. In this animal, however, the corpus luteum was not completely developed prior to the infusion. From this study it can be concluded: 1) intrauterine iodine infusions performed after the development of a progesterone secreting corpus luteum result in prostaglandin release within three to six days with the subsequent occurrence of luteolysis; 2) luteolysis wras in all cases observed in connection with prostaglandin F2α release of the same order of magnitude and duration as during normal luteolysis. kw|Keywords|k]prostaglandin release; k]progesterone; k]cow; k]es trous cycle; k]iodine infusion     

Physiological role of 20alpha-dihydroprogesterone during the estrous cycle in goats

The relationships between the effects of single or repeated subcutaneous injections of 25 mg progesterone on luteal function during the estrous cycle in goats as well as the secretion of 20alpha-dihydroprogesterone or 15-keto-13, 14-dihydro-prostaglandin F(2alpha) (PGFM), the major metabolite of PGF(2alpha), were investigated. A single dose of progesterone given on Day 4, 10, or 18 of the estrous cycle increased the concentration of 20alpha-dihydroprogesterone and did not affect the length of the cycle. Each dose of progesterone on Days 2 to 5 increased the concentration of 20alpha-dihydroprogesterone (with a later decrease each day to a nadir which then increased daily) and shortened the cycle. The 20alpha-dihydroprogesterone concentration remained high; when it decreased, the concentration of the luteolytic agent PGFM began to increase. Daily doses of 25 mg 20alpha-dihydroprogesterone given on Days 2 to 5 had no effect on the length of the cycle. These results indicate that during the estrous cycle in goats, progesterone is catabolized to the biologically inactive steroid 20alpha-dihydroprogesterone, but much of the progesterone that is given early in the luteal phase of the estrous cycle causes premature luteolysis by stimulating an increase in the release of PGF(2alpha) . The secretion of 20alpha-dihydroprogesterone may help to regulate progesterone production during the estrous cycle in goats.     

Corpus luteum regression induced by ultra-low pulses of prostaglandin F2α

In view of the pulsatile nature of PGF_2α secretion from the ovine uterus at the time of luteolysis, experiments were designed to examine the effect of pulsed infusions of PGF_2α on luteal function and to re-examine the minimal effective levels of PGF_2α required to induce luteolysis. To mimic physiological conditions, hour-long infusions of PGF_2α in increasing concentrations were given either 4 times in 19 h or 5 times in 25 h into the arterial supply of the autotransplanted ovary in conscious sheep on day 12 of an induced cycle. Blood flow and progesterone secretion rate from the ovary were used to monitor directly the luteolytic effect of administered PGF_2α. The concentration of LH in peripheral plasma was measured throughout each infusion experiment and the presence of a preovulatory peak of LH was used as an indicator of the permanence of luteal regression. Four pulses of PGF_2α in 19 h caused complete corpus luteum regression in only 1 of 4 animals whereas the addition of a fifth pulse (5 pulses in 25 h) caused permanent regression in 4 out of 4 animals. Infusion of 5 hour-long pulses of saline or PGF_2α at a rate of <0.04 μg/h did not induce permanent suppression of progesterone secretion. The average total effective dose of PGF_2α required to induced luteal regression when given as 5 pulses was 1/40th of the amount currently regarded as the minimal effective one when given by constant infusion into the ovarian artery. In another series of experiments the luteolytic effect of a single hour-long pulse of 0.1 μg/h PGF_2α given daily for either 3 or 4 days was investigated. A significant fall (ANOVA, F_0.01) in progesterone secretion rate, which reached a nadir at $\text{5.3 ± 2.2}\text{h (}\text{x}\text{±}\text{S.D.}\text{, n=15)}$, was followed by a recovery of progesterone secretion rate. Permanent luteal regression did not occur with this protracted regimen, suggesting that a relatively short pulse frequency of PGF_2α over a minimal period of 24 h is a necessary condition for physiological regression of the corpus luteum in sheep.     

Reduction by human chorionic gonadotropin of the luteolytic effect of prostaglandin F2 in ewes

The ability of human chorionic gonadotropin (HCG) to reduce the luteolytic effect of prostaglandin (PGF_2^α) was demonstrated in cycling ewes. As expected, treatment with 10 mg of PGF_2^α alone on Day 10 of the estrous cycle exerted a potent negative effect on the function and structure of corpus luteum (CL) as indicated by reduced plasma progesterone, CL progesterone, and CL weight. However, the identical PGF_2^α treatment failed to significantly reduce either luteal function or luteal weight when administered to ewes that were also treated with HCG on Days 9 and 10 of the estrous cycle. Treatment with HCG alone had a positive effect on CL as indicated by increased plasma progesterone, CL progesterone, and CL weight. Treatment with HCG did not render the CL totally insensitive to the negative effects of PGF_2^α because plasma progesterone was reduced when the dose of PGF_2^α was doubled. Whether CL regressed or continued to function after treatment with both HCG and PGF_2^α appeared to depend upon a balance between the positive and negative effects of the two hormones.     

Sparing effects of intrauterine treatment with prostaglandin E2 on luteal function in cycling gilts

Twelve crossbred gilts, 8 to 9 months of age, were used to study the effects of prostaglandin E₂ (PGE₂) on luteal function during the estrous cycle. Intrataurine and jugular vein catheters were surgically placed before day 7 of the treatment estrous cycle and gilts were randomly assigned to 1 or 3 treatment groups. Groups I and II received constant intrauterine infusion of vehicle (6.0 ml/24 hr) or PGE₂ (2400 μg/day; 6.0 ml/24 hr) respectively; while group III was given intrauterine infusions of 400 μg PGE₂ every 4 hr. All infusions were initiated on day 7 and continued until estrus or through day 23. Jugular blood samples were collected twice daily from days 7 to 30 for progesterone analysis. Intrauterine infusion of PGE₂ at the dose and frequencies given in this study delayed the decline in jugular plasma progesterone and resulted in prolongation of the estrous cycle length. The results of this study have shown that PGE₂ at the dosage and frequency of administration used was capable of extending corpus luteum function.     

Comparative luteolytic activity of estradiol cyclopentylpropionate and prostaglandin F2α in diestrous cows

The effect of estradiol cyclopentylpropionate (EC) on corpus luteum (CL) function in diestrous cows was evaluated. Two doses of EC (4 and 20 mg) were given by intramuscular (IM) injection and one dose of EC (4 mg) was given by intrauterine (IU) infusion. Control cows were treated with physiologic sterile saline (PSS) IU or corn oil IU (negative controls) or prostaglandin F_2α (PGF_2α, 30 mg IM, positive control). A total of 24 cows, four per treatment, were treated on days 8 to 12 of the estrous cycle (day 0 equals day of estrus). Luteal function was monitored by serum progesterone through 96 hours after treatment. A decrease in serum progesterone from pretreatment diestrous concentrations to less than 1.0 ng/ml was considered indicative of luteolysis.Intrauterine injection of PSS and corn oil had no effect on luteal function. Neither IM nor IU administration of EC caused consistent or rapid luteolytic effects. Prostaglandin F_2α consistently induced rapid luteal regression. These results indicate that EC should not be considered luteolytic in the same sense as is PGF_2α.     

Comparative study of the concentrations of peripheral progesterone before and after PGF2α injection between Bos taurus (Brown Swiss) and Bos indicus (Indobrazil) in the tropics

With the object of studying the changes in progesterone concentration during the oestrous cycle and of verifying prostaglandin F_2α (PGF_2α) response in the luteal phase, 10 Indobrazil and 6 Brown Swiss cows, all non-lactating, were bled three times a week during the months of March and April in the Mexican tropics.Progesterone levels in both groups followed a similar pattern, maximum mean levels being reached at day 13 of the cycle (Indobrazil 2.2 ng/ml and Brown Swiss 2.8 ng/ml). No significant differences were found in the progesterone levels throughout the cycle. Nevertheless, a highly significant difference (P < 0.001) was established between breeds with respect to progesterone levels before and after PGF_2α injection. This was possibly due to a seasonal effect on progesterone production in the two types of cow.     

Prostaglandin-induced regression of porcine corpora lutea maintained by estrogen

Corpora lutea were marked with suture in 24 crossbred gilts on day 7 to 9 of the estrous cycle (first day of estrus = 0). All gilts were injected with 5 mg of estradiol benzoate (EB) daily from day 10 to 15 to extend the lifespan of corpora lutea, then the gilts were randomly assigned to two groups. On day 20, the 12 gilts of Group 1 were injected with 10 mg PGF_2α, and the 12 gilts of Group 2 were injected with saline. Ovaries were recovered 10 to 13 days after PGF_2α or saline injection. Ten gilts in Group 1 displayed estrus 5 ± 0.7 days after PGF_2α injection, but only two gilts in Group 2 displayed estrus during the experimental period. In gilts that displayed estrus, all marked CL had regressed. Marked CL were still present in all 12 gilts that failed to exhibit estrus during the experimental period. These results show that in the pig, PGF_2α caused regression of CL that were maintained beyond the normal luteal phase of the estrous cycle by EB treatment.     

Prostaglandin E2 opunteracts the effects of PGF2α in indomethacin treated cycling gilts

Twenty crossbred gilts with at least 2 consecutive estrous cycles of 18 to 21 days in length were used to study the effects of prostaglandins E₂ and F₂α (PGE₂ and PGF₂α) on luteal function in indomethacin (INDO) treated cycling gilts. Intrauterine and jugular vein catheters were surgically palced before day 7 of the treatment estrous cycle and gilts were randomly assigned to 1 of 5 treatment groups (4/groups). With exception of the controls (Group I) all gilts received 3.3 mg/kg INDO every 8 h, Groups III, IV and V received 2.5 mg PGF₂; 2.5 mg PGF₂α + 400 μg PGE₂ every 4 hr, or 400μg PGE₂ every 4 h, respectively. All treatments were initiated on day 7 and continued until estrus or day 23. Jugular blood for progesterone analysis was collected twice daily from day 7 to 30. Estradiol-17β (E₂-17β) concentrations were dtermined in samples collected twice daily, from 2 d before until 2 d following the day of estrus onset. When compared to pretreatment values, estrous cycle length was unaffected (P>0.05) in Group I, prolonged (P<0.05) in Groups II, IV and V; and shortened (P<0.05) in Group III. The decline in plasma progesterone concentration that normally occurs around day 15 was unaffected (P>.05) in Group I; delayed (P<0.05) in Groups II, IV and V; and occurred early (P<0.05) in Group III. Mean E₂-17β remained high (31.2 ± 4.9 to 49.3 ± 3.1 pg/ml) in Groups III and IV, while the mean concentrations in Groups III and V varied considerably (17.0 ± 2.0 to 52.2 ± 3.5 pg/ml). The results of this study have shown that PGE₂ will counteract the effects of PGF₂α in INDO treated cycling gilts. The inclusion of PGF₂α appeared to either stimulate E₂-17β secretion or maintain it at a higher level than other treatments.     

Sparing effects of intrauterine treatment with prostaglandin E2 on luteal function in cycling gilts

Twelve crossbred gilts, 8 to 9 months of age, were used to study the effects of prostaglandin E2 (PGE2) on luteal function during the estrous cycle. Intrauterine and jugular vein catheters were surgically placed before day 7 of the treatment estrous cycle and gilts were randomly assigned to 1 of 3 treatment groups. Groups I and II received constant intrauterine infusion of vehicle (6.0 ml/24 hr) or PGE2 (2400 micrograms/day; 6.0 ml/24 hr) respectively; while group III was given intrauterine infusions of 400 micrograms PGE2 every 4 hr. All infusions were initiated on day 7 and continued until estrus or through day 23. Jugular blood samples were collected twice daily from days 7 to 30 for progesterone analysis. Intrauterine infusion of PGE2 at the dose and frequencies given in this study delayed the decline in jugular plasma progesterone and resulted in prolongation of the estrous cycle length. The results of this study have shown that PGE2 at the dosage and frequency of administration used was capable of extending corpus luteum function.     

Circulating concentrations of oxytocin during the estrous cycle and early pregnancy in sheep

Plasma concentrations of oxytocin and progesterone have been measured by radioimmunoassay in jugular venous blood obtained daily from 5 sheep during 2 estrous cycles and in early pregnancy.Concentrations of oxytocin were relatively high (15–30 pg/ml) during the luteal phase of the cycle, but fell at estrus (to 1–17 pg/ml). A fall in oxytocin was also observed on day 15 of pregnancy, when, as expected, progesterone levels remained high. It is suggested that raised basal levels of oxytocin are unlikely to cause the increasing uterine release of prostaglandin F_2α which occurs at the end of the estrous cycle.     

Utero-ovarian venous concentrations of prostaglandin E2 (PGE2 and prostaglandin F2α (PGF2α) following PGE2 intrauterine infusions

The uterine horns and utero-ovarian veins of nine crossbred mature gilts were bilaterally cannulated on day 9 of the estrous cycle (day 0 - first day of estrus). Each uterine horn in treated gilts (N=5) was infused with 150 μg PGE₂ in 3 ml of saline at 0900 h on day 12, 15 and 18 of the estrous cycle. Control gilts (N=4) received 3 ml saline intrauterine infusions on the corresponding day. Blood samples were collected from the utero-ovarian veins 15 min before each infusion and for the following 6 h with 15, 30 and 60 min intervals through the first, second and third two-hour periods, respectively. Venous concentrations of PGE₂ and PGF_2α were determined by radioimmunoassay procedures. Infusion of PGE₂ resulted in an immediate elevation in PGE₂ concentration in utero-ovarian venous drainage. Coincident elevations of PGF_2α utero-ovarian venous concentrations were observed after PGE₂ infusion. Plasma PGF_2α concentrations in the utero-ovarian veins were elevated (P<.01) in PGE₂ treated gilts for one hour post-treatment. The duration of PGE₂ and PGE₂α elevations as well as the peak values were influenced by day of the cycle.     

Prostaglandin E1 and F2α specific binding in bovine corpora lutea: Comparison with luteolytic effects

Preliminary characterization indicated the presence of separate prostaglandin (PG)E₁ and (PG)F_2α binding sites in membrane fractions prepared from bovine corpora lutea. These differ in the rate and temperature dependence of the specific binding. Equilibrium binding data indicate the apparent dissociation constants as 1.32 × 10⁻⁹M and 2.1 × 10⁻⁸M for PGE₁ and PGF_2α, respectively. Competition of several natural prostaglandins for the PGE₁ and PGF_2α bovine luteal specific binding sites indicates specificity for the 9-keto or 9α-hydroxyl moiety, respectively. Differences in relative ability to inhibit ³H-PG binding were found due to sensitivity to the absence or presence of the 5,6-cis-double bond as well.Bovine luteal function was affected following treatment of heifers with 25 mg PGF_2α as measured by reduced estrous cycle length, decreased corpus luteum size and significantly decreased plasma progesterone levels. In contrast, treatment with 25 mg PGE₁ resulted in cycle lengths comparable to those of non-treated herdmates with no apparent modification in corpus luteum size. However, plasma progesterone levels were increased significantly following PGE₁ treatment compared to pretreatment values. In so far as data obtained on PGF_2α relative binding affinity to the bovine CL can be compared to data obtained independently on PGF_2α induced luteolysis in the bovine, PGF_2α relative binding to the CL and luteolysis appeared to be associated. By similar reasoning, there was no apparent relationship between PGE₁ relative binding affinity in the luteal fractions and luteolysis in estrous cyclic cattle.     

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.     

Prostaglandin F2α back transfer from the mesometrium vasculature into the uterus of the gilt during early pregnancy and estrogen-induced pseudopregnancy

Isolated reproductive tracts from gilts on the days of luteal regression (13–17 day of estrous cycle), pregnant gilts (14–18 days of pregnancy) and estrogen-induced pseudopregnant gilts (15–18 day of estrous cycle) were supplied with autologous, oxygenated blood. ³H-PGF_2α (10⁸ dpm) was infused at a constant rate into three different sites of the most superficial layer of the myometrium along the length of the horn close to the broad ligament. During infusion (60 min) and 60 min after the infusion had been stopped, arterial blood was collected continuously in 5-min samples from a small branch of the uterine artery in the mesometrium area about 10 cm from the uterine horn. A significantly higher concentration of ³H-PGF_2α in the uterine-artery blood plasma was found in pseudopregnant and pregnant gilts than in the control group. The total ³H-PGF_2α back transfer with arterial blood from the broad ligament vasculature into the uterus was 2.4 × 10⁶ dpm, 6.0 × 10⁶ dpm and 19.8 × 10⁶ dpm of infused ³H-PGF_2α in the control, pregnant and pseudopregnant gilts, respectively. We suggest that ability for PGF_2α binding and back transfer from the broad ligament vasculature into the uterus, as observed in pseudopregnant and pregnant gilts, may strongly reduce the peak concentration during the pulsatile release of PGF_2α from the uterus and may protect the corpus luteum against luteolysis.     

Effect of progesterone administration on the release of uterine prostaglandin F2α and ovarian oxytocin in the goat

The effects of intramuscular progesterone administration (20 mg·day⁻¹) on plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM-pulmonary metabolite of prostaglandin F_2α) and oxytocin were examined in seventeen goats after either bilateral ovariectomy, hysterectomy or during days 12–16 of the estrous cycle. Daily mean values of PGFM in animals treated with progesterone after ovariectomy were significantly greater (P<0.001) than in their corresponding controls on the last two treatment days (10 and 11); concentrations of oxytocin, however, remained at or near the limits of assay sensitivity. In hysterectomized goats PGFM concentrations remained extremely low and oxytocin release appeared steady rather than pulsatile. In the intact animals, undergoing luteolysis, daily mean concentrations of both PGFM and oxytocin were significantly greater (P<0.01) in progesterone-treated goats than in their oil-treated controls; furthermore, in the progesterone-treated goats, increases in PGFM concentrations, observed after the peaks of progesterone, were either coincident with or prior to pulses of oxytocin. These results demonstrate that uterine PGF_2α stimulates the pulsatile release of oxytocin from the ovary during luteolysis in the goat.