The effects of prostaglandin F2α on sperm output in boars

The effect of prostaglandin F_2α (PGF_2α) on the sperm output of six boars was investigated in two studies. Although PGF_2α did not significantly affect sperm numbers in the ejaculate, a significantly longer (P < 0.05) ejaculation of the sperm rich fraction occurred following injection of PGF_2α. In the second study it was found that PGF_2α produced a 49% increase (P < 0.05) in the number of sperm in the sperm rich fraction of the ejaculate. The implications of these results on artificial breeding are discussed.     

Increased blood LH and testosterone after administration of prostaglandin F2α in bulls

Two types of experiments were conducted to determine the relationship of changes in blood luteinizing hormone (LH) and testosterone in bulls given prostaglandin F_2α (PGF_2α). Episodic surges of LH and testosterone occurred in tandem, apparently at random intervals, on the average once during the 8-hr period after bulls were given saline. In contrast, after sc injection of 20 mg PGF_2α, blood serum testosterone increased synchronously to a peak within 90 minutes four-fold greater than pre-injection values, and the testosterone surges were prolonged about three-fold compared to those in controls. Each of the PGF_2α-induced surges of testosterone was preceded by a surge of blood serum LH which persisted for about 45 minutes and peaked at about 3 ng/ml. In a second experiment, PGF_2α was infused (iv, 0.2 mg/min) for 20 hr; blood plasma testosterone increased from 7.0 ± 0.6 to 16.0±1.5 ng/ml within 2.5 hr and remained near this peak for 10 hr. Then testosterone gradually declined to about 9 ng/ml at the conclusion of the 20-hr infusion. These changes in testosterone were paralleled by similar changes in blood plasma LH, although LH declined 3 hr earlier than testosterone. Random episodic peaks of blood plasma LH and testosterone typical of untreated bulls resumed within 8 hr after conclusion of PGF_2α infusion. In both experiments, the surge of testosterone after PGF_2α was preceded by increased blood LH. We conclude that increased LH after administration of PGF_2α probably caused the increased testosterone. However the mechanisms of these actions of PGF_2α remain to be determined.     

Radioimmunoassays of prostaglandin F2α and prostaglandin F2α-main urinary metabolite with prostaglandin-I-tyrosine methylester amide

Radioimmunoassays for measuring prostaglandin F_2α (PGF_2α) and 5α, 7α-dihydroxy-11-keto tetranorprosta-1,16-dioic acid, PGF_2α-main urinary metabolite (PGF_2α-MUM), with ¹²⁵I-tyrosine methylester amide (TMA) of PGF_2α and PGF_2α-MUM were developed.Antibody to PGF_2α was produced in rabbits immunized with conjugates of PGF_2α coupled to bovine serum albumine. Antibody to PGF_2α-MUM was also produced in rabbits immunized with conjugates of PGF_2α-MUM coupled to bovine serum albumin.PGF_2α-¹²⁵I-TMA had an affinity to antiserum to PGF_2α. PGF_2α-MUM-¹²⁵I-TMA also responded to antiserum to PGF_2α-MUM.     

Sperm output and serum testosterone in rabbits given prostaglandin F2α or E2

Two experiments were conducted, the first to compare sperm output and the second to determine serum testosterone in rabbits given PGF₂α or PGE₂. In the first, six rabbits were ejaculated twice each Monday, Wednesday and Friday for 5 weeks. Each rabbit was given subcutaneously (sc) each of the following treatments five times: 1) saline, 2) 5 mg PGF₂α and 3) 5 mg PGE₂. Treatments were given, half at 4 hr and half at 2 hr before first ejaculations. Both PGF₂α and PGE₂ caused increased (50% and 84%) sperm content of first ejacula, without significantly altering characteristics of second ejacula. The extra sperm in first ejacula was a function of increased sperm density, because seminal volume was unaltered.In the second experiment, 15 rabbits were bled at 0.5-hr intervals for 9 hr and given (sc): 1) saline at 1 and 3 hr (n=4), 2) 2.5 mg PGF₂α at 1 and 3 hr (n=4), 3) 2.5 mg PGE₂ at 1 and 3 hr (n=4) or 4) 5 mg PGF₂α at 1 hr after the onset of blood sampling. In saline-treated controls, episodic surges of testosterone occurred on the average every 5 hours. After the injection of 2.5 or 5.0 mg PGF₂α, serum testosterone began to rise at 0.5 hr, peaked (8 to 13 ng/ml) at 1 hr and approached a nadir (0.5 ng/ml) within 4 hours. The second injection of 2.5 mg PGF₂α failed to significantly affect serum testosterone. PGE₂ treatment was followed by significantly depressed serum testosterone; only 1 of these 4 rabbits had any surge of testosterone for the 8 hr after treatment. In conclusion, PGF₂α and PGE₂ both increased sperm output, but PGF₂α increased serum testosterone while PGE₂ depressed serum testosterone. Thus, the sperm output effect of these prostaglandins probably is independent of the acute changes in testosterone secretion.     

Effect of prostaglandin F3α on gastric mucosal injury by ethanol in rats: Comparison with prostaglandin F2α

In humans eicosapentaenoic acid can be converted to 3-series prostaglandins (PGF_3α, PGI₃, and PGE₃). Whether 3-series prostaglandins can protect the gastric mucosa from injury as effectively as their 2-series analogs is unknown. Therefore, we compared the protective effects of PGF_3α and PGF_2α against gross and microscopic gastric mucosal injury in rats. Animals received a subcutaneous injection of either PGF_3α or PGF_2α in doses raning from 0 (vehicle) to 16.8 μmol/kg and 30 min later they received intragastric administration of 1 ml of absolute ethanol. Whether mucosal injury was assessed 60 min or 5 min after ethanol, PGF_3α was significantly less protective against ethanol-induced damage than PGF_2α. These findings indicate that the presence of a third double bond in the prostaglandin F molecule between carbons 17 and 18 markedly reduces the protective effects of this prostaglandin on the gastric mucosa.     

Effects of indomethacin, prostaglandin E2, prostaglandin F2α and 6-keto-prostaglandin F1α on hatching of mouse blastocysts

The present study has been performed to investigate how PGs would participate the hatching process. Effects of indomethacin, an antagonist to PGs biosynthesis, on the hatching of mouse blastocysts were examined in vitro. Furthermore, it was studied that prostaglandin E₂ (PGE₂), prostaglandin F_2α (PGF_2α) or 6-keto-prostaglandin F_1α (6-keto-PGF_1α) were added to the culture media with indomethacin. (1) The hatching was inhibited by indomethacin yet the inhibition was reversible. (2) In the groups with indomethacin and PGE₂, no improvement was seen in the inhibition of hatching and the inhibition was irreversible. (3) In the groups with indomethacin and PGF_2α, inhibition of hatching was improved in comparison with the group with indomethacin. (4) In the groups with indomethacin and 6-keto-PGF_1α, no improvement was seen. The above results indicated that PGF_2α possibly had an accelerating effect on hatching and a high concentration of PGE₂ would exert cytotoxic effect on blastocysts.     

The enzymatic conversion of prostaglandin D2 to prostaglandin F2α

Prostaglandins E₂ and D₂ were both converted to prostaglandin F_2α (9α, 11α) by an enzyme present in sheep blood. Neither the 9β, 11α epimer nor the 9α, 11β epimer was produced from PGE₂ or PGD₂ respectively. The rate of reduction was measured using isotope dilution (D₄ PGF_2α) and multiple-ion detection gas chromatography-mass spectrometry.     

Termination of pregnancy in cats with prostaglandin F2α

Two subcutaneous injections of Prostaglandin F_2α THAM salt 24 hours apart terminated pregnancies in cats after the 40th day of gestation. Injections of 0.50 or 1.00 mg. PGF_2α THAM salt/Kg. body weight were the most effective in terminating pregnancies. Parturition or abortion occurred within 24 hours after the initial injection in 9 cats and after the 2nd injection in 4 cats.     

Intra-amniotic prostaglandin F2α and urea for abortion

Prostaglandin F_2α (PGF_2α) 20 mg combined with urea 80 g was injected intra-amniotically in 20 patients to induce mid-trimester abortion. Abortion resulted in all subjects within 24 hours in a mean time of 12 hours 38 minutes (range 5 hours 50 minutes to 20 hours 45 minutes).Plasma sex steroids were evaluated before and hourly for 5 hours after the injection. A progressive decline in levels occurred with time. Decreases in plasma progesterone, estrone, estradiol and estriol were significant as soon as one hour after injection.Gastrointestinal side effects occurred with a greater frequency than when a comparable dose of PGF_2α is given alone and 2 patients had small cervical lacerations requiring suture. Further studies are indicated to establish whether a lower dose of PGF_2α will be associated with fewer side effects and be as effective.     

Urinary excretion of prostaglandin E2 and prostaglandin F2α in potassium-deficient rats

Potassium-deficiency was induced in rats by dietary deprivation of potassium. The animals became polyuric and urine osmolality decreased more then three-fold compared to controls. Urinary excretion of prostaglandin E₂ (PGE₂) and prostaglandin F_2α (PGF_2α) did not increase during 2 weeks of potassium depletion. Partial inhibition of renal prostaglandin synthesis by meclofenamate did not increase the urine osmolality after water deprivation. These results make unlikely the hypothesis that the polyuria of potassium-deficiency, is the result of enhanced renal synthesis of prostaglandins with subsequent antagonism of the hydro-osmotic effect of vasopressin. Male animals consistently excreted less PGE₂ than female animals.     

Influence of prostaglandin F2α on sperm production and seminal characteriticss of the stallion

Six mature stallions were used to test the effect of prostaglandin F_2α (PGF_2α) on sperm production and seminal characteristics. Semen was collected from each stallion twice weekly 1 hr following a 10 mg intramuscular injection of PGF_2α or a sham injection. A switchback design was used so that three stallions received PGF₂ and three served as controls during the first 9 weeks (period 1). Threatment regimens were reversed during the second 9 weeks (period 2). Treatment of stallions with PGF_2α resulted in an increase (/prmP<.05) in gel free seminla voume and a decrease in sperm cell concentration. Total spermatozoa, sperm cell motility, and percentage of primary and secondary sperm abnormalities or ejaculates were not significantly affected by treatment of stallions with PGF_2α before semen collection. All treated stallions exhibited a pronounced sweating response to the drug. During the experiment, two of the six stallions masturbated within 20 to 30 minutes after PGF_2α treatment without achieving an erection.     

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.     

Intracellular recording of cerebral cortical actions of prostaglandin F2α (PGF2α)

Our reported data on the cortical inhibitory actions of prostaglandin F_2α (PGF_2α) and the diversity of data in the literature on cerebral PG actions are examined here in the light of intracellular recording which provides the requisite membrane data for the first time. Thus, 1) intracellular recording from the cat cerebral cortex is obtained for the actions of PGF_2α and for norepinephrine (NE) and serotonin (5HT). 2) The parallel changes in firing and polarization and the simultaneous transmembrane conductance changes are qualitatively identical for PGF_2α, NE and 5HT. 3) The reduction in firing accompanied by hyperpolarization indicates that PGF_2α, NE and 5HT all inhibit these cells. 4) The ionic species responsible for this inhibition is such that it increased the transmembrane resistance, and this was true for all three. 5) The changes in membrane parameters, identical in direction for PGF_2α and NE, but stronger for the latter, constitute conditions that can lead to competitive inhibition and therefore conote, presumably, actions at the same or related receptors. Such competition with evoked cortical field potentials is shown in the preceding paper.     

Determination of prostaglandin F2α, E2, D2 and 6-keto-F1α in human cerebrospinal fluid

Prostaglandin (PG)F_2α, E₂, D₂ and 6-keto-F_1α were determined in human cerebrospinal fluid by a mass spectrometric technique. The samples were obtained from 12 patients with suspected intracranial disease. A 64 fold variation in PG levels was observed. The major PG was 6-keto-F_1α (0.12–15 ng/ml). PGF_2α and PGE₂ were present in lower concentrations PGD₂ was below the level of detection (0.05 ng/ml) except in one patient with extremely high total levels of PGs.     

Intrauterine instillation of prostaglandin F2α in early pregnancy

Intrauterine PGF_2α (5mg) was administered for termination of early pregnancy in 14 healthy volunteers. With 11 complete abortions, the efficiency rate of this technique is below conventional methods. In addition, the incidence of infection was high occurring in 12 out of 14 subjects. Because of persistent bleeding, six patients underwent a dilatation and curettage. Other significant side effects included transient hypertension, pain, nausea and restlessness. In the patients with a complete abortion, the mean plasma progesterone concentration fell 37% after 8 hours post PGF_2α instillation and 90% 14 days later. The mean plasma estradiol-17β fell 26% over the initial eight hour period and 75% over the next 14 days.     

Viroimmunoassay of prostaglandin F2α at the picogram level

A viroimmunoassay of PG F_2α is presented here. By a modification of the technique used by Dray et al. (3), it allowed us to measure as low as one picogram of PG F_2α. It seems that such a sensitive assay might be usefull for many purposes in the prostaglandin field.     

Cardiac arrhythmias induced by prostaglandin F2α in cats

Intravenous administration of prostaglandin F_2α results in transient episodes of sinus bradycardia in anesthetized cats. In addition, ventricular bigeminy was observed in approximately 40% of those cats anesthetized with pentobarbital (36 mg/kg) and 58% of those anesthetized with chloralose (70 mg/kg). This arrhythmogenic effect of PGF_2α is abolished following bilateral vagotomy, indicating that the arrhythmias are most likely due to a marked stimulation of vagal tone in this species.     

The excretion of prostaglandin F2α in milk of cows

Prostaglandin F_2α (PGF_2α) was measured by immunoassay in plasma and milk of four cows (six experiments). After 30 mg PGF_2α im, plasma PGF_2α peaked at 15 minutes (2.4 ± 0.7 ng/ml) and declined toward basal values by 3 hours; maximum milk PGF_2α (0.91 ± 0.12 ng/ml) occurred at 1 hour. The average excretion rate in milk was 2.9 μg/day 0.9 μg (0.003%) of which was due to the 30 mg PGF_2α injected. In six non-pregnant control cows, daily changes of milk PGF_2α and progesterone were not consistently related.     

15-methylation augments the cardiovascular effects of prostaglandin F2α

Intramuscular injection of the 15-methyl analogue of prostaglandin F_2α (15-me-PGF_2α) is being used to initiate second trimester abortion. The natural prostaglandin F_2α (PGF_2α) is a known pulmonary pressor agent but there is little information about the cardiovascular effects of the analogue. Consequently, we compared the hemodynamic responses to the two forms in twenty-three anesthetized dogs. Given I.M. or I.V. 15-me-PGF_2α produced a greater and more sustained rise in pulmonary arterial pressure than PG F_2α. Intramuscular 15-me-PGF_2α also elicited a more prolonged increase in pulmonary vascular resistance than prostaglandin F_2α given I.M. or I.V. The methyl analogue (I.M. or I.V.) causes a greater initial fall in systemic arterial oxygen tension and cardiac output, and a greater increase in systemic resistance than I.M. PG F_2α Breathlessness seen during abortion induced by prostaglandin F_2α or its methyl analogue may be caused by acute pulmonary hypertension in addition to bronchoconstriction.