Midterm abortion in hamsters induced by Silastic-PVP-PGE2 tubes

Intrauterine insertion of a 0.5 cm long Silastic-PVP tube containing 750 μg PGE₂ (lyophilized sodium salt) caused midterm abortion in hamsters within 48 hours. An earlier study using a similar Silastic-PVP tube delivery system showed that 200 μg of PGF_2α (Tham) was sufficient to induce abortion in 100% of pregnant hamsters (18). Prostaglandin E₂ is, therefore, about 3.5–4 times less potent than PGF_2α as an abortifacient in the hamster. The release of ³H-PGE₂ from Silastic-PVP tube and is also described. It is suggested that an increase in LH release might be one of the factors leading to luteolysis; and that either PGE₂ exerts a direct luteolytic effect or this effect is manifested after its being converted to PGF_2α.     

Effect of mifepristone and antiestrogens on uterine PGF2α and PGE2 concentrations in ovariectomized and pregnant rats

Four antiestrogens (anordiol, tamoxifen, RU 39411, ICI 182780) and the antiprogestin, mifepristone (RU 486), were administered to the following three animal models: (1) ovariectomized rats, (2) mated rats treated post-coitally; and (3) pregnant rats treated post-implantation. The antiestrogens were administered alone or in combination with mifepristone at doses effective in preventing and/or terminating pregnancy in rats. The objective of the study was to determine whether these drugs influenced uterine concentrations of prostaglandins (PGF_2α and PGE₂).Antiestrogens administered alone to ovariectomized rats did not effect uterine PGE₂ or PGF_2α concentrations; whereas the combination of anordiol/mifepristone increased uterine PGF_2α concentration, resulting in an increase in the PGF_2α/PGE₂ ratio.Mated rats were treated post-coitally for three consecutive days with anordiol, tamoxifen, estradiol and mifepristone alone and with the combination of anordiol/mifepristone and tamoxifen/mifepristone. An increase in uterine PGF_2α concentrations and in the PGF_2α/PGE₂ ratio occurred only in anordiol/mifepristone treated group. A decrease in uterine PGE₂ concentrations occurred in animals treated with anordiol, tamoxifen and estradiol, resulting in an increase in the PGF_2α/PGE₂ ratio.Anordiol (5.0 mg/kg/day) and mifepristone (4.0 mg/kg/day) alone and the combination of anordiol/mifepristone (2.5/1.0 mg/kg/day) administered to pregnant rats on days 7, 8 and 9 of pregnancy induced an increase in PGF_2α levels without affecting uterine PGE₂ concentration. The changes in uterine PGF_2α concentrations induced by anordiol and the combination of anordiol/mifepristone resulted in an increase in the PGF_2α/PGE₂ ratio.The antiestrogens tested except for ICI 182780 possessed agonist activity when assayed by measuring their capacity to increase the uterine weights in ovariectomized rats. Also, ICI 182789 was the only antiestrogen that did not influence uterine PG concentrations. It can be concluded that ICI 182780 is the only “pure” antiestrogen among those tested.The present results show that antiestrogens and the combination of mifepristone plus anordiol at doses preventing implantation and terminating pregnancy increase uterine PGF_2α and/or decrease PGE₂ concentrations, resulting in an alteration of PGF_2α/PGE₂ ratio. These findings suggest that there exists a critical balance of PGF_2α to PGE₂ concentrations in the uterus required for the normal passage of fertilized ova through the oviduct, initiating implantation of the blastocysts, development of embryos, and maintenance of pregnancy.     

Effects of 17 β estradiol on the metabolism of labelled arachidonic acid in uteri isolated from intact and ovariectomized rats. Influence of a restricted diet

The effects of restricted diet (50% of the normal intake during 25 days) on the metabolism of ¹⁴U arachidonic acid, were explored in uterine horn strips isolated from intact and ovariectomized rats, treated by 17 β-estradiol or controls. The metabolism of arachidonic acid into different eicosanoids, PGE₂, PGF_2α, 6-keto PGF_1α and TXB₂, showed that the restricted diet diminished PGE₂ and PGF_2α, in intact rats, significantly. In contrast, this kind of feeding did not produce any change in castrated rats.Tissue preparations from previously estrogenized intact and castrated normal-fed rats showed that the production of different metabolites decreased. A similar result was obtained in intact rats subjected to a restricted diet. Nevertheless, in castrated underfed rats, estrogens did not produce any effect on the various eicosanoids analysed.These results showed that in isolated uteri, the effects of 17 β-estradiol, on metabolite production from labelled arachidonic acid, are different from controls in ovariectomized diet-restricted rats.     

On the mechanism of action of 15-methyl-PGF2α as an abortifacient

Several hours following administration of long acting vaginal suppositories containing 3.0 mg of 15-methyl-PGF_2α for interruption of second trimester pregnancies there is an up to 10-fold increase in endogenous production of PGE₂ and PGF_2α before abortion as reflected by gas chromatographic-mass spectrometric determination of the major plasma metabolites of PGE₂ and PGF_2α. The data suggest that this increased formation of endogenous prostaglandins contributes to the induced uterine activity during the latter part of the abortion process.     

Histamine alters prostaglandin output from diestrous rat uteri. Involvement of H2-receptors and 9-keto-reductase

The effects of exogenous histamine (H) on prostaglandin (PG) generation and release in uteri isolated from diestrous rats and the influences of H₂-receptors blockers (cimetidine and mitiamide) on the output of uterine PGs, were explored. Moreover, the action of H on the uterine 9-keto-reductase, was also studied. Histamine (10⁻⁴M) failed to alter the basal output of PGE₁ but reduced significantly the generation and release of PGE₂ and augmented the output of PGF_2α. On the other hand, cimetidine (10⁻⁵M) enhanced the basal release of PGE₂ but had no action on the outputs of PGs E₁ or F_2α. The enhancing effect of H on the production and release of PGF_2α was abolished in the presence of cimetidine. Also, the antagonist reversed the influence of H on the output of PGE₂. Metiamide, another H₂-receptor antagonist, did not alter the basal control generation and release of uterine PGs, but antagonized the augmenting influence of H on PGF_2α uterine output, as much as cimetidine did, and prevented the depressive action of H on the release of PGE₂ from uteri. Histamine (10⁻⁴M) significantly stimulated uterine formation of cyclic-adenosine monophosphate, an action which was antagonized by the presence of cimetidine (10⁻⁵M), a blocker of H₂ receptors. Also, histamine (10⁻⁵M) and dibutyril-cyclic-adenosine monophosphate (DB-cAMP) at 10⁻³M, enhanced significantly the formation ³H-PGF_2α from ³H-PGE₂. Results presented herein demonstrate that H is able to diminish the generation of PGE₂ in uteri from rats at diestrus augmenting the synthesis of PGF_2α, apparently via the activation of H₂-receptors, enhancing adenylate-cyclase. These effects appear to increase uterine 9-keto-reductase activity which transforms PGE₂ into PGF_2α. Relationships between the foregoing results and those evoked by estradiol, are also discussed.     

Prostaglandin (PG) analysis in urine of humans and rats by different radioimmunoassays: Effect on PG-excretion by PG-synthetase inhibitors, laparotomy and furosemide

Thw radioimmunological (RIA) determination of prostaglandin (PG) E₂ and of PGF_2α in urine humans and rats is described in detail. After extraction and chromatography PGE₂ was determined by using a PGE specific antibody or by using either PGB or PGF_2α specific antibodies after the respective conversion procedures. The three different RIA procedures were compared to each other. PGF_2α was determined by a specific antibody to PGF_2α. Basal excretion of PGE₂ and of PGF_2α in healthy women on free diet was 9.3 ng/hour ± 0.96 and 18.3 ng/hour ± 2.5 respectively. Furosemide increased the excretion of PGE₂ and of PGF_2α in humans significantly, while PG-excretion rates decreased on indomethacin. In rat urine PGE₂ and PGE_2α increased markedly from 46.2 pg/min ± 9.3 and 27 ± 3.4 to 253.8 ± 43.3 and 108 ± 12.6 pg/min (per one kidney) in the anesthetized-laparotomized animal. This increase was abolished after giving two different PG synthetase inhibitors.     

Hyperglycemia promotes elevated generation of TXA2 in isolated rat uteri

The relationship between high glucose concentrations and arachidonic acid metabolism in uterine tissue from control and diabetic ovariectomized rats was evaluated. Uterine tissue from diabetic rats produced amounts of PGE₂ and PGF_2α similar to controls, while a lower production of 6-keto-PGF_1α (indicating the production of prostacyclin) and a higher production of TXB₂ (indicating the generation of TXA₂) was found in the diabetic group. A group of diabetic rats was treated with phlorizin to diminish plasma glucose levels. Phlorizin treatment did not alter production of PGE₂, PGF_2α, and 6-keto-PGF_1α in the diabetic group. A diminished production of TXB₂ was found in the treated diabetic uteri when compared to the non-treated diabetic group. Moreover, a positive correlation between plasma glucose levels and uterine TXB₂ generation was observed. When control uterine tissue was exposed in vitro to high concentrations of glucose (22 mM) and compared to control tissue incubated in the presence of glucose 11 mM alterations in the generation of PGE₂, PGF_2α, and 6-keto-PGF_1α were not found, but a higher production of TXB₂ was observed and values were similar to those obtained in the diabetic tissue. Alteration in the production of the prostanoids evaluated were not observed when diabetic tissue was incubated in the presence of high concentrations of glucose. These results provide evidence of a direct relationship between plasma glucose levels and uterine production of TXA₂.     

Radioimmunological and biological measurement of prostaglandins in rabbit urine : Decrease of PGE2 excretion at high NaCl intake

The estimation of prostaglandin (PG) E₂ and of PGF_2α by radioimmunoassay is described in detail. PGE₂ was measured after conversion to either PGB₂ or PGF_2α and the results compared to bioassay. The methods were used to follow the excretion of PGE₂ and PGF_2α after salt loading in rabbits. A marked reduction of PGE₂ levels was observed at high NaCl intake, while PGF_2α excretion remained unchanged.     

The effects of prostaglandins PGE1, PGE2, PGF1a, and PGF2a on canine synovial perfusion

In these experiments we have examined the effects of PGE₁, PGE₂, PGF_1α and PGF_2α on synovial perfusion in the normal canine synovial microcirculation. The effects of the drugs on synovial perfusion were determined indirectly from the changes produced in the rate of clearance of ¹³³Xenon from the joint by their intra-articular injection. Prostaglandins PGE₁ and PGE₂ were found to be strongly vasodilator with PGE₁ being the more active. PGF_1α appeared to have little or no vasoactive properties in doses up to 1 ugm. (2.8 × 10^−5M) in our I preparation while PGF_2α was vasodilator at this high dosage only. Neither SC19920 nor diphloretin phosphate antagonised the effects of PGE₁ in these experiments.     

Prostaglandin biosynthesis by the rat uterus during the oestrus cycle, temporal correlation with plasma oestradiol and progesterone concentrations, identification of 6 keto PGF1α as the major metabolite

Prostaglandin biosynthesis was studied in the rat uterus during the oestrous cycle. Uterine homogenates were incubated for 20 minutes in the presence of exogenous substrate (2.10⁻⁵M). PGF_2α and PGE₂ were measured by R.I.A.. A sharp peak PGF_2α and a smaller peak of PGE₂ were observed at prooestrus, 20 h. Another small PGE₂ peak occurred at dioestrus II, 15 h. The lowest values of both PGs were found on dioestrus, 15 h. Plasma oestradiol concentration were highest at proestrus, 15 h and 20 h. A sharp progesterone peak occurred at prooestrus, 20 h. The PGF_2α peak is next to the oestradiol peak and is superimposable or lags slightly beyond the progesterone peak.Incubation with ¹⁴C arachidonic acid and subsequent analysis of extracts by TLC and scanning showed that the major metabolite is PGI₂, identified as 6 keto PGF_1α. The conversion rate of arachidonic acid into 6 keto PGF_1α is 5 times higher than into PGF_2α. 6 keto PGF_1α was further identified by GC/MS. No significant difference was observed between 6 keto PGF_1α production during oestrus and dioestrus.     

Prostaglandins and thromboxanes in amniotic fluid during rivanol-induced abortion and labour

Abortion or delivery were induced by extra-amniotic instillation of Rivanol during the second trimester in twelve patients and during the third trimester in two patients with fetal death and one patient with fetal acrania. Serial sampling of amniotic fluid was performed through a transabdominal catheter and the levels of free arachidonic acid (AA), prostaglandin F₂α (PGF₂α), prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (6-keto-PGF₁α) and thromboxane B₂ (TXB₂) were determined. The levels of AA, PGF₂α, PGE₂, 6-keto-PGF₁α and TXB₂ in amniotic fluid increased significantly during induction with the exception of AA in fetal death which was high and remained constant during induction. Furthermore, PGF₂α, 6-keto-PGF₁α and TXB₂ were all significantly correlated to AA.These observations suggested that free AA is released during Rivanol-induction of abortion and labour giving an increased synthesis of PGF₂α, PGE₂ prostacyclin and thromboxane A₂ in the fetal membranes and the decidua but not in the fetus. This increase might be relevant for the initiation and progress of abortion and labour in these patients.     

Influence of sex hormones on prostaglandin dehydrogenase activity in the rat uterus

The present experiments report the effects of estradiol or of progesterone on the activity of 15-prostaglandin-dehydrogenase (PGDH) in the uterus of spayed rats. When the substrate was PGF_2α the treatment with progesterone (4 mg.day⁻¹, two days) or with estradiol-17-beta (0.5 ug + 1 ug) did not show any effect on the activity of the enzyme. On the contrary, uteri from ovariectomized rats injected with a higher dose of estradiol- 17-beta (0.5 ug + 50 ug) exhibited a significant increment. When the substrate was PGE₂, progesterone failed again to modify the enzyme activity, whereas estradiol, both at a low and at a high doses, enhanced significantly the uterine PGDH activity. The possibility of two different PGDHs for each PG and the role of estradiol in enhancing PGE₂ catabolism into 15-keto- PGE₂ as a mechanism subserving the effect of estrogens on the output of this PG in the rat uterus, are discussed.     

Characterization and ontogeny of PGE2 and PGF2α receptors on the retinal vasculature of the pig

The vasoconstrictor effects of PGE₂ and PGF_2α are less pronounced on retinal vessels of the newborn than of the adult pig. We tested the hypothesis that the decreased vasomotor response to these prostaglandins might be due to relatively fewer receptors and/or different receptor subtypes (in the case of PGE₂) on retinal vessels of the newborn animal. Binding studies using [³H]PGE₂ and [³H]PGF_2α revealed that PGE₂ (EP) and PGF_2α (FP) receptor densities in retinal microvessel membrane preparations from newborn animals were approximately 25% of those found in vessels from the adult. The K_d for PGF_2α did not differ; however, the K_d for PGE₂ was less in newborn than in adult vessels. Competition binding studies using AH 6809 (EP₁ antagonist), butaprost (EP₂ agonist), M&B 28,767 (EP₃ agonist), and AH 23848B (EP₄ antagonist) suggested that the retinal vessels of the newborn contained approximately equal number of EP₁ and EP₂ receptor subtypes whereas the main receptor subtype in the adult vessels was EP₁. In addition, PGE₂ and butaprost produced comparable increases in adenosine 3′,5′-cyclic monophosphate synthesis in newborn and adult vessels. PGE₂, 17-phenyl trinor PGE₂ (EP₁agonist) and PGF_2α caused a 2.5 to 3-fold greater increase in inositol1,4,5-triphosphate (IP₃) formation in adult than in newborn preparations. It is concluded that fewer PGF_2α receptors and an associated decrease in receptor-coupled IP₃ formation in the retinal vessels of the newborn could lead to weaker vasoconstrictor effects of PGF_2α on retinal vessels of the newborn than of adult pigs; fewer EP₁ receptors (associated with vasoconstriction) and a relatively greater proportion of EP₂ receptors (associated with vasodilation) might be responsible for the reduced retinal vasoconstrictor effects of PGE₂ in the newborn.     

Prostaglandin release from the guinea-pig uterus superfused in vitro. Effect of stage of estrous cycle, progesterone, estradiol, oxytocin and A23187

Prostaglandin (PG) E₂ was the major PG released from the superfused guinea-pig uterus on Day 7, followed by in descending order 6-oxo-PGF_1α, thromboxane (TX) B₂ and PGF_2α. However, the outputs of all four substances were low and were very similar. By Day 15, PGF_2α output from the superfused uterus had increased 21.9-fold, whereas the outputs of PGE₂, 6-oxo-PGF_1α and TXB₂ had increased only 1.8-, 2.9- and 1.2-fold, respectively. A mechanism is apparently “switched on” between Days 7 and 15 which causes a fairly specific increase in the release of PGF_2α from the uterus.Progesterone and/or estradiol had no effect on PG or TX release when superfused over the uterus on Day 7, nor did they have any effect on PG and TX release from the Day 15 uterus when administered separately. When administered together, however, they significantly inhibited PGF_2α, PGE₂ and 6-oxo-PGF_1α, but not TXB₂, release from the Day 15 uterus. Oxytocin had no effect on PG release from the Day 7 or Day 15 uterus, while A23187 stimulated PGF_2α, 6-oxo-PGF_1α and, to a lesser extent, PGE₂ release from the uterus on both Days 7 and 15 Oxytocin is apparently not important for stimulating PGF_2α release from the guinea-pig uterus in relation to luteolysis, whereas increasing intracellular free Ca⁺⁺ levels may be part of the mechanism for “switching on” uterine PG synthesis. Furthermore, changes in intracellular free Ca⁺⁺ levels in the endometrium may be responsible for the pulsatile nature of PGF_2α release from the uterus.     

Prostaglandin synthesis by the cochlea

The exogenous and endogenous syntheses of prostaglandins (PG's) by the cochlea of adult mongolian gerbils were studied . After incubation of the whole membraneous cochlea with [³H]-arachidonic acid (AA), syntheses of PGF_2α, 6-keto PGF_1α, PGE₂, thromboxane (TX) B₂ and PGD₂ were evidenced in this order. The synthesis of radioactive PG's was almost completely inhibited by incubation with 10⁻⁵ M indomethacin. No significant amounts of those PG's were detected by radioimmunoassay (RIA) in the cochlea obtained from animals killed by microwave irradiation at 5.0 kw for 0.8 sec. However, when the homogenate of the whole membraneous cochlea obtained from animals without microwave irradiation was incubated at 37°C for 0–15 min, PGD₂, PGE₂, PGF₂α and 6-keto PGF₁α were found to be formed from endogenous AA in the cochlea by RIA. PG's were formed already at 0 time to considerable level (PGD₂, PGF₂α and 6-keto PGF₁α, 90–120 pg/cochlea; PGE₂, 370 pg/cochlea), reached to the maximum level (PGD₂, PGF₂α and 6-keto PGF₁α, 170–200 pg/cochlea; PGE₂, 500 pg/cochlea) at a 5-min incubation, and then gradually decreased. On the other hand, the amount of TXB₂ was lower than the detection limit by RIA (<50 pg/cochlea) even after the incubation. The cochlea was dissected into three parts: organ of Corti + modiolus (OC + M), lateral wall (LW), and cochlear nerve (CN), and then PG's formed by these tissues were determined after a 5-min incubation of the homogenates. In the CN and OC + M, PGE₂ was the major PG (100 and 160 pg/tissue, respectively), and the amounts of PGD₂, PGF₂α and 6-keto PGF₁α were about of those of PGE₂. In the LW, the amounts of PGD₂, PGE₂, PGF₂α and 6-keto PGF₁α were about the same level (70–100 pg/LW).     

Biological activities of 17-phenyl-18,19,20-trinorprostaglandins

In a number of assay ssytems, some 17-phenyl-trinor prostaglandins were similar in activity and potency to the corresponding parent prostaglandin. In others, the 17-phenyl analogs appeared several times more potent. In the hamster antifertility assay, which is considered to measure luteolytic activity, 17-phenyl-18,19,20-trinor prostaglandin F_2α was about 90-times PGF_2α in potency.Rat blood pressure responses to 17-phenyl analogs were significant. The 17-phenyl-trinor PGF_2α pressor potency was 5 times that of PGF_2α. The 17-phenyl-trinor PGE₂ blood pressure response was atypical since a pressor rebound phenomenon followed the expected depressor response. Lastly, 17-phenyl-trinor PGF_2α was more potent than PGF_2α in synchronizing the estrous cycle in beef cows.     

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.     

In vivo inhibition of the human non-pregnant uterus by prostaglandin E2

The discrepancy between the effect of PGE₂ on the non-pregnant myometrium (relaxation) as compared to (stimulation) has not yet been solved. Nine women in the early post-menopause volunteered for the investigation. Prostaglandin (PG) F_2α or E₂ was administered either by single intravenous (i.v.) injection or by intra-uterine instillation and the uterine contractility was recorded by the microballoon technique. The response of the menopausal uterus to i.v. injections of PGF_2α or PGE₂ was characterized by rapid stimulation while intra-uterine instillation of PGF_2α induced gradual but sustained elevation of uterine tonus. However, the intra-uterine injection of PGE₂ caused inhibition of different components of uterine contractility. The fact that PGE₂ can also inhibit the motility of the menopausal non-pregnant uterus coincides with earlier results i.e. the discrepancy may not exist. Moreover, in one cycling patient (13–18th days of the menstrual cycle) similar results were also obtained. Two theories were offered to explain why PGE₂ stimulated the uterus when given as a single i.v. injection but inhibited the same organ when instilled locally into the uterine cavity.     

Stereospecificity of enzymatic reduction of prostaglandin E2 to F2α

Antibodies directed toward PGF_2β were prepared in rabbits. The serologic specificity of the immune reaction was determined by inhibition of sodium borohydride-reduced (³H) PGE₂ anti-PGF_2β binding by several prostaglandins. The antibodies to PGF_2β recognize the β-hydroxyl configuration in the cyclopentane ring of PGF_2β. With the use of both anti-PGF_2α and anti-PGF_2β, the product of PGE₂ reduction by 9-ketoreductase purified from chicken heart was identified as PGF_2α. Guinea pig liver and kidney homogenates were examined for PGE 9-ketoreductase activity. Although enzyme activity was present, no evidence of PGF_2β production was found.     

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 in vitro on PGF_2α relative binding affinity to the bovine CL can be compared to data obtained independently in vitro 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.