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.     

Evidence for separate PGD2 and PGF2α receptors in the canine mesenteric vascular bed

Potential interactions between PGD₂ and PGF_2α in the mesenteric and renal vascular beds were investigated in the anesthetized dog. Regional blood flows were measured with electromagnetic flow probes. PGD₂, PGF_2α and Norepinephrine (NE) were injected as a bolus directly into the appropriate artery, and responses to these agents were obtained before, during and after infusion of either PGD₂ or PGF_2α into the left ventricle. In each case, the infused prostaglandin caused vascular effects of its own. Left ventricular infusion of PGD₂ reduced responses to local injections of PGD₂ in the intestine, and a similar effect was observed for PGF_2α, suggesting significant receptor or receptor-like interactions for each of the prostanoids. However, systemic infusion of prostaglandin F_2α (20–100 ng/kg/min) had no effect on renal or mesenteric vascular responses to local injection of prostaglandin D₂. Similarly, PGD₂ administration (100 ng/kg/min) did not affect responses to PGF_2α in the intestine. The present results therefore suggest that these prostaglandins, i.e., D₂ and F_2α, act through separate receptors in the mesenteric and renal vascular beds. In addition, increased prostaglandin F_2α levels produced by infusion of F_2α reduced mesenteric but not renal blood flow, suggesting that redistribution of cardiac output might participate in side effects often observed with clinical use of this prostaglandin, such as nausea and abdominal pain.     

Evaluation of the role of the F prostaglandins in canine bile flow

Prostaglandin F_2α (PGF_2α) has been shown to be an effective stimulant of hepatic bile flow producing a specific chloride rich bile. Subsequent evaluation by radioimmunoassay has shown that prostaglandin F compounds are present in relatively large amounts in canine hepatic bile. This study evaluates the effect of PGF_2α administration and of prostaglandin synthetase inhibition by aspirin and indomethacin on bile flow and radioimmunoassayable prostaglandin F (iPGF) secretion. Chronic, canine bile fistula preparations were utilized and the enterohepatic circulation was maintained by intravenous bile salts. Bile volume and composition were evaluated by standard techniques as well as bile PGF concentration by radioimmunoassay during bile salt infusion and during bile salt and PGF_2α, aspirin and indomethacin infusion in varying doses. Both aspirin and PGF_2α were potent stimulatns of hepatic bile flow with aspirin producing a chloride rich bile similar to that produced by PGF_2α. PGF_2α produced dose related increases in bile iPGF concentration and output indicating that as the systemic concentration increases during infusion of PGF_2α the lipid appears in bile. Aspirin in the highest dose administered, decreased iPGF concentration in bile while output was unchanged. Indomethacin was ineffectual in consistently altering bile flow or iPGF secretion. This study demonstrates that iPGF is present in canine bile, that its concentration can be altered by prostaglandin infusion while prostaglandin synthetase inhibition has minimal effects on bile iPGF secretion.     

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.     

Induction of term labor with intravenous prostaglandin F2α (a comparison of two dosage schedules)

The efficacy of intravenous Prostaglandin F_2α (PGF_2α) infusion for induction of labor in two different dosage schedules was studied in 90 women between 36 and 43 weeks of gestation. The rate of PGF_2α infusion was increased at four-hour intervals in 36 women in the low dosage group and every hour in 54 women in the high dosage group, never exceeding an infusion rate of 20 μg/min. in either group. Labor was successfully induced in approximately 90% of the patients in each group. There was no statistically significant difference in the mean induction-delivery interval between the two groups at the 5 percent level. Intravenous PGF_2α was found to be effective and safe for both mother and infant in the dosage schedules used in this study for induction of labor.     

Dose-dependent effects of a pyridoquinazoline thromboxane synthetase inhibitor on arachidonic acid metabolites and hemodynamics during E. Coli endotoxemia in anesthetized sheep

We investigated the effects of a new pyridoquinazoline thromboxane synthetase inhibitor infused before administering endotoxin into 18 anesthetized sheep with lung lymph fistulas. In normal sheep increasing plasma Ro 23-3423 concentrations were associated with increased plasma levels of 6-keto-PGF_1α, a reduced systemic vascular resistance (SVR, r = −0.80) and systemic arterial pressure (SAP, r = −0.92), the mean SAP falling from 80 to 50 mm Hg at the 20 and 30 mg/kg doses. Endotoxin infused into normal sheep caused transient pulmonary vasoconstriction associated with increased TxB₂ and 6-keto-PGF_1α levels while vasoconstriction and TxB₂ increase were significantly inhibited by pretreatment with Ro 23-3423 in a dose-dependent manner. When compared to controls, plasma and lymph levels of 6-keto-PGF_1α, PGF_2α and PGE₂ after endotoxin infusion were increased several-fold by administering Ro 23-3423 up to plasma levels of 10 μg/ml. Doses over 30 mg/kg with blood levels above 10 μg/ml reduced plasma and lymph levels of 6-keto-PGF_1α, PGF_2α and PGE₂, suggesting cyclooxygenase blockade at this dose. The peak 6-keto-PGF_1α levels at 60 min after endotoxin infusion in sheep with Ro-23-3423 levels below 10 μg/ml were associated with the greatest systemic hypotension due to a reduced SVR (r = −0.86). After endotoxin infusion the leukotrienes B₄, C₄, D₄ and E₄ in lung lymph were assayed by radioimmunoassay and high pressure liquid chromatography and remained at baseline values.     

Mating increases plasma levels of prostaglandin F2α in female garter snakes

Plasma levels of prostaglandin F_2α (PGF_2α) in female red-sided garter snakes (

Full-size image (<1K)

) were measured at intervals after mating or exposure to males. PGF_2α levels increased significantly within 15 minutes of mating and peaked 6–24 hr after mating. Females that did not mate, but received similar amounts of male courtship, had levels of PGF_2α significantly lower than those of females that mated. These results extend previous findings that unmated female garter snakes injected with PGF_2α exhibit sexual behavior characteristics of females that have mated. Together these data indicate that female garter snakes elaborate PGF_2α in response to stimuli associated with mating and that PGF_2α has a functional role in inducing post-mating declines in sexual behavior of this species.     

Effects of dibuturyl cAMP, LHRH, and aromatase inhibitor on simultaneous outputs of prostaglandin F2α, and 13,14-dihydro-15-keto-prostaglandin F2α by term placental explants

Explants from term human placentas were maintained in culture with daily changes of medium. Daily output of PGF_2α and PGFM¹ decreased during the course of the incubation. Addition of 4 μg/ml DHEAS or 67 μg/ml LDL cholesterol had no effect on output of PGF_2α or PGFM. Addition of 1.6, 3.2, or 6.4 μg/ml of LHRH to the culture plates had no effect on output of PGFM or PGF_2α, but LHRH increased hCG output. Dibutyryl cAMP (1mM, 2mM, and 4mM) increased output of PGF_2α, PGFM, and hCG. Aromatase inhibitor decreased hCG output, but it was without effect on output of PGF_2α, or PGFM. Significant correlations were demonstrated between progesterone, PGFM, PGF_2α, and hCG, suggesting that PGF_2α originates in the syncytiotrophoblast cell. The ability of LHRH to stimulate output of hCG but not PGF_2α while dbcAMP stimulated both suggests that either PGF_2α and hCG arise in different cells or that LHRH does not act through cAMP.     

Central and peripheral circulatory effects and metabolic effects of different prostaglandins given I.V. to man

Cardiac output, heart rate, stroke volume, pressures in the brachial artery, right ventricle and pulmonary artery, forearm blood flow, and arterial concentration of FFA, lactate and glucose were measured in healthy male volunteers during i–v infusion of PGE₁, PGE₂, PGF_2α or 15-methyl PGF_2α in increasing doses. In accordance with previous findings PGE₁ and PGE₂ increased cardiac output by a vasodilating effect in the systemic and pulmonary vascular bed, probably in combination with an inotropic effect on the heart.15-methyl PGF_2α had essentially the same cardiovascular effects as PGF_2α. They induced a slight increase in cardiac output due to effects on heart rate, while systemic vascular resistance was unchanged. Forearm vascular resistance increased and pressures in the pulmonary circulation rose, indicating a vasoconstriction in these vascular beds.Glucose concentrations were not affected nor were lactate concentrations, except for a slight decrease of unclear significance in the group receiving 15-methyl PGF_2α. FFA increased slowly in the same manner as seen spontaneously in fasting individuals. These data do not indicate direct metabolic effects of the prostaglandins studied when given i–v.     

The effect of intrauterine administration of prostacyclin on the contractility of the non-pregnant uterus in vivo

Prostacyclin was infused into the uterus of non-pregnant women either during early menstruation or in the secretory phase of the cycle. A dose of 5 μ/min produced little systemic effect and caused a significant decrease in uterine activity on Days 1 and 2 of the menses whereas 0.5 μg/min did not. However, when dysmenorrhoeic pain and increased uterine activity were produced by infusion of PGF_2α during the secretory phase, PGI₂ neither decreased the activity nor the pain. This indicates that PGI₂ does not cause uterine relaxation by blocking the action of PGF_2α.     

Relationships among mammalian gonadotropin-releasing hormone, prostaglandins, and sex steroids in the brain of the crested newt, Triturus carnifex

The present study was carried out to evaluate the in vitro brain release of prostaglandin F_2α (PGF_2α), prostaglandin E₂ (PGE₂), androgens, and 17β-estradiol in male and female crested newt, Triturus carnifex, during three different periods of the annual sexual cycle; in addition, the effects of mammalian gonadotropin-releasing hormone (mGnRH), PGF_2α, and PGE₂ on prostaglandins and steroids release by the brain were evaluated during the same periods. In brain incubations of both sexes, PGF_2α and estradiol were higher during postreproduction, while PGE₂ and androgens were higher during reproduction. In both sexes, mGnRH increased PGF_2α and estradiol during postreproduction, and PGE₂ during reproduction; PGF_2α increased estradiol secretion during postreproduction. Only in the male, did both mGnRH and PGE₂ increase androgens during reproduction. It could be suggested that in Triturus carnifex, the regulation of the reproductive activity in the central nervous system (CNS) depends on the relationships among mGnRH, prostaglandins and steroids. In particular, PGF_2α and PGE₂ seem to play different roles in the CNS of the newt: PGF_2α is involved in the postreproductive processes, through estradiol secretion, while PGE₂ in the reproductive ones (through androgens secretion?).     

Oviduct response to prostaglandins: Influence of estradiol and progesterone

Oviductal motility was measured in the isthmus of ovariectomized New Zealand rabbits. The effects of estradiol and progesterone on spontaneous motility and on the response of the oviduct to exogenously administered prostaglandin E₁ (PGE₁) and PGF_2α were determined. Estradiol treatment significantly increased both the amplitude (P<0.05) and frequency (P<0.01) of spontaneous contractions. The amplitude of spontaneous activity was less following progesterone treatment than following estradiol treatment (P<0.05). Progesterone treatment increased the duration of oviduct response to PGE₁ (P<0.05). Estradiol treatment had no effect on the response to PGE₁. Increased oviductal activity caused by PGF_2α lasted significantly (P<0.01) longer in ovariectomized, untreated animals than in ovariectomized animals treated with estradiol or progesterone. Progesterone was more effective than estradiol in decreasing the duration of the response to PGF_2α. These effects of steroid hormones on the responsiveness of the oviduct to PGE₁ and PGF_2α could contribute to the physiological control of egg transport. The nadir of ovarian hormone influence, as in the recently ovariectomized animals and as occurs immediately after ovulation, is associated with a high responsiveness of the oviduct to PGF_2α. This could effectively increase isthmic occlusion and prevent the eggs from passing through the oviduct prematurely. The gradual increase in ovarian estradiol and progesterone secretion during the 3 days following coitus could result in decreased responsiveness to PGF_2α and increased responsiveness to PGE₁. These changes might cause relaxation of isthmic tone and allow movement of eggs through the isthmus into the uterus.     

The effects of prostaglandins, prostaglandin inhibitors, and oxygen on the closure of the ductus arteriosus, pulmonary arteries and umbilical vessels in vitro

Three prostaglandins (PGF₂α and PGE₁, PGE₂) have been found in maternal and fetal circulation during labour. Two of these prostaglandins (PGF₂α and PGE₂) are present in elevated levels in maternal circulation during labour and their presence in fetal vessels has been shown.These three prostaglandins have been tested for their effects on fetal vessels in vitro (umbilical artery and vein, ductus arteriosus, and smaller pulmonary artery). These vessels were selected as being crucial in the conversion from fetal to extra-uterine circulation in mammalian species. Responses of these vessels to the prostaglandins under varying oxygen regimes have been examined as well as their responses to prostaglandin inhibitors. Activity of vessels of varying gestational ages exposed to PGF₂α was also examined. The following results were obtained:

1. All vessels, with the exception of pulmonary arteries, contracted in the presence of oxygen over the range 20–100mmHg pO₂. At a pO₂ of < 20mmHg the ductus arteriosus remained inactive or dilated. Pulmonary arteries dilated at high pO₂.

2. All vessels contracted in response to exogenous PGF₂α with the exception of the pulmonary arteries which dilated. In the presence of PGF₂α, the umbilical veins dilated under low (< 20mmHg) pO₂ and contracted at higher levels. Contraction also occurred at lower levels after a period of time.

3. Although PGF₂α was capable of causing contraction in the ductus arteriosus at near zero pO₂, oxygen, (or possibly the products of oxygenation), appear to be required for continued contraction in the presence of PGF₂α. A synergistic relationship between oxygen and PGF₂α responses was found as oxygen tensions increased. A synergistic response between PGF₂α and oxygen with umbilical arteries which did not increase with increased pO₂ was also found. Oxygen tension appeared to have little effect on the response of other vessels to PGF₂α.

4. PGE₁ caused dilations in all vessels examined. Such dilations appearing to be independent of the oxygen regime prevailing. However, an increase in oxygen during experiments reversed any dilation caused by the prostaglandins.

5. PGE₂ caused contractions in umbilical vessels which were independent of oxygen. PGE₂ caused contraction of pulmonary arteries. However, in the ductus arteriosus, PGE₂ caused an initial contraction followed by a strong dilation. This dilation became weaker as pO₂ increased.

6. Additions of prostaglandin inhibitors (Naproxen and Indomethacin) to the bathing solution in which the ductus arteriosus and umbilical arteries were contracting (in response to PGF₂α, or oxygen alone) caused a decrease in contractions, and sometimes a slight decrease when the vessel had been pretreated with PGF₂α suggesting a possible need for endogenously synthesised prostaglandins for the maintenance of oxygen mediated contractions (in vivo).

7. Vessels responsed to PGF₂α at an early gestational age. A role for prostaglandins and oxygen in the closure of fetal vessels is discussed.

     

Prostaglandin F2α increases responsiveness of pulmonary airways in dogs

We studied the effect of prostaglandin F_2α (PGF_2α) on the responsiveness of pulmonary airways in dogs. Airway responsiveness was assessed by determining the bronchoconstrictor response to increasing concentrations of acetylcholine aerosol delivered to the airways. In each of five dogs, we determined responsiveness during treatment with physiologic saline, histamine, or PGF_2α aerosols. The doses of histamine and PGF_2α were determined by establishing the largest dose of each which could be given to the dog without causing bronchoconstriction (subthreshold doses). We found that airway responsiveness was not significantly different during histamine treatment than after saline, however, responsiveness increased during treatment with PGF_2α. In addition, the hyperresponsiveness induced by PGF_2α was prevented by pretreatment with the ganglion blocking drug hexamethonium (5 mg/kg given intravenously). The results show that PGF_2α specifically increases the responsiveness of pulmonary airways in doses that do not cause bronchoncostriction, and suggest that the hyperresponsiveness involves a neural mechanism such as increased responsiveness of airway sensory nerves.     

Effect of prostaglandin F2α on uterine or ovarian secretion of prostaglandins E and F2α in vivo in 90–100 day hysterectomized, intact or ovariectomized pregnant ewes

Vehicle or 8 or 16 mg of PGF_2α per 58 kg body weight was given intramuscularly to intact, hysterectomized or ovariectomized 90–100 day pregnant ewes in three separate experiments. Both doses of PGF_2α increased PGF_2α in ovarian venous plasma compared with controls at 72 hr post treatment in intact (P≤0.05) but did not in hysterectomized (P≥0.05) 90–100 day pregnant ewes. Concentrations of PGE in ovarian venous blood of intact ewes did not differ (P≥0.05) between treatment groups and were equivalent to concentrations of PGE determined in uterine venous plasma. PGE was decreased in ovarian venous plasma by PGF_2α in hysterectomized ewes (P≤0.07). PGE in uterine venous plasma averaged 6 ng/ml over the 72-hr treatment period in intact and ovariectomized 90–100 day pregnant ewes and was 12 fold greater (P≤0.05) than PGF_2α which averaged 500 pg/ml in uterine venous plasma. Both PGF_2α and PGE increased (P≤0.05) by 64 hr in uterine venous plasma of the 8 mg PGF_2α — treated intact pregnant ewes. A significant quadratic increase (P≤0.05) was observed for PGF_2α and PGE in the vehicle and both PGF_2α treatment groups of intact ewes at the end of the 72-hr sampling period. It is concluded that the uterus and ovaries secrete significant quantities of PGE but little PGF_2α during midgestation. In addition, PGF_2α increased uterine secretion of PGE . PGE may be a placental stimulator of ovine placental secretion of progesterone or PGE may protect placental steroidogenesis from actions of PGF_2α.     

Changes in corpus luteum content of prostaglandin F2α and E in the adult pseudopregnant rat

Conflicting reports exist regarding the source of luteolytic PGF_2α in the rat ovary. To assess the quantities of different PGs, measurements of PGF_2α, PGE and PGB were performed by radioimmunoassay in the adult pseudopregnant rat ovary throughout the luteal lifespan. Ovaries of 84 rats were separated by dissection into two compartments, corpora lutea of pseudopregnancy and remainder of ovary. Tissue samples were homogenized and prostaglandins extracted and determined by radioimmunoassay. During the mid-luteal and late-luteal phases, levels of PGs were significantly higher in the corpora lutea of pseudopregnancy than in the remainder of ovary. An increase of PGF_2α-content in the corpus luteum was registered with peak-levels of 53.9 ± 8.5 (mean ± SEM, N=18) ng/g tissue wet weight at day 13 of pseudopregnancy. PGE-levels reached peak-values at day 11 of pseudopregnancy (271.6 ± 28.4 ng/g w w, mean ± SEM, N=12). PGB-levels were below detection limits in all compartments for all ages studied. The present study demonstrates increased availability of PGF_2α in the corpus luteum during the luteolytic period, and points toward either increased luteal synthesis or luteal binding of PGF_2α during the luteolytic period.     

Elongation of oestrous cycle in the guinea-pig following active immunisation against prostaglandin F2α

Five guinea-pigs actively immunised against a PGF_2α-bovine serum albumin conjugate showed elongated cycles, whereas 5 control animals injected with a mixture of PGF_2α and bovine serum albumin showed no change in cycle length. These results are compatible with the hypothesis that the uterine luteolytic hormone in the guinea-pig is PGF_2α.     

Effect of PGF2α on progesterone secretion and adenylate cyclase activity in ovine luteal tissue

Ovine luteal slices were used to study the effects of prostaglandins (PG) F₂α on luteinizing hormone (LH)-stimulated secretion of progesterone and adenylate cyclase activity. The accumulation of progesterone in incubation medium and adenylate cyclase activity was similar after incubation of luteal slices with Medium 199 alone or Medium 199 containing PGF₂α (250 ng/ml) for 3 hr. Addition of luteinizing hormone (LH; 100 ng/ml) resulted in a 2–3 fold increase in both the rate of progesterone accumulation and adenylate eyclase activity by 3 hr. When luteal slices were incubated in the presence of both LH and PGF₂α the rates of progesterone accumulation and adenylate cyclase activity were identical to those in flasks containing LH alone after 1 hr; however, after 3 hr both LH stimulated progesterone accumulation and adenylate cyclase activity were inhibited to levels similar to those observed in control slices.In a second experiment, after 60–120 min of exposure to PGF₂α the rate of progesterone accumulation in the medium was not different from that in untreated control slices. In addition, after this experiment the luteal slices were homogenized and the basal, sodium fluoride, LH, isoproterenol (ISO) and PGE₂ sensitive adenylate cyclase activities were determined to evaluate the hormonal specificity of the negative effect of the pretreatment with PGF₂α. Both LH and ISO stimulated adenylate cyclase activities were reduced after PGF₂α pretreatment. However, fluoride ion stimulated adenylate cyclase activity was not significantly effected by PGF₂α pretreatment and PGE₂ sensitive adenylate cyclase was effected only slightly.     

The effect of indomethacin on the biosynthesis and metabolism of prostaglandin F2α in man

Healthy volunteers received 60 μg of [8,10,10-²H₃] PGF_2α by intravenous infusion both before and during a course of treatment with indomethacin (200 mg/day). Excretion of deuterated 5α, 7α-dihydroxy-11-ketotetranor-prostane-1, 16-dioic acid in urine was quantified by GC-MS using a reverse stable isotope dilution procedure. Indomethacin was found to have no detectable effect on the metabolism of the labelled PGF_2α whereas output of the endogenous metabolite was markedly reduced by the effect of the drug on prostaglandin biosynthesis.     

Luteolysis, estrus and ovulation, and blood prostaglandin F after intramuscular administration of 15, 30 or 60 mg prostaglandin F2α

During diestrus in three consecutive estrous cycles, each of six heifers was given (im) 30 mg, 15 mg (twice at 6-hr intervals) and 60 mg prostaglandin F_2α (PGF_2α) tham salt. Neither the decline in blood progesterone, the increase in blood estradiol, the duration or the peak of the LH surge, the interval to onset of estrus, nor the interval to ovulation was affected significantly by dose of PGF_2α. Thus, relative to that after 30 mg PGF_2α im, two injections of 15 mg at 6-hr intervals or 60 mg PGF_2α did not hasten luteolysis. Thirty mg was an ample im dose of PGF_2α to cause luteolysis. Regardless of im dose of PGF_2α, blood PGF peaked at about 6.0 ng/ml within 10 minutes and returned to basal values (<1.0 ng/ml) within 90 minutes. In another trial, after a single iv injection of 5 mg PGF_2α, blood PGF peaked (25 ng/ml) within 5 minutes and returned to basal values within 15 minutes. During a 30-minute infusion (0.5 mg/minute) of PGF_2α, blood PGF plateaued at 29.5 ng/ml with a metabolic clearance rate of 17.0 liters per minute.