Release of endogenous prostaglandins by mild hyperosmotic saline inhibits tetragastrin-stimulated gastric acid secretion in rats

Filling of the gastric lumen of rats with 1.0 M NaCl solution (5 ml) for 10 min under urethane anesthesia caused an increase in the gastric fluid concentrations of prostaglandin (PG) E₂, 13, 14-dihydro-15-keto-PGE₂ and 6-keto-PGF_1α as determined by radioimmunoassay. PGE₂ was the major PG generated. The levels of PGE₂ in the gastric fluid were increased dose-dependently after filling the lumen with 0.3, 0.5, 0.7 or 1.0 M NaCl solutions. The pH of the gastric fluid increased similarly after 0.5 to 1.0 M NaCl solutions. Indomethacin (10 mg/kg, i.p.) suppressed the PGE₂ increase caused by 1.0 M NaCl solution, but did not prevent the increase of the pH of the gastric fluid induced by intragastric 1.0 M NaCl. Infusion of tetragastrin (62.5 μg/kg/hr, i.v., for 10 min) caused a marked increase of acid secretion without modifying intragastic concentration of PGE₂. The acid secretion due to tetragastrin was completely inhibited after intragastric administration of 1.0 M NaCl solution, while indomethacin restored the tetragastrin-induced acid secretion, with prevention of a rise of intragastric PGE₂ levels. These observations suggest that 1.0 M NaCl solutions suppress basal intragastric acid through a mechanism which is independent of prostaglandins. In contrast, the suppression of tetragastrin-induced acid secretion by intragastric 1.0 M NaCl solution appears to be mediated through a release of prostaglandins     

The effect of prostaglandins E1, E2, F1 alpha and F2 alpha on pig erythrocytes during haemolysis induced with aspirin and hypotonic NaCl solution

The effect of prostaglandins PGE1, PGE2, PGF1 alpha and PGF2 alpha was investigated on the haemolysis of pig erythrocytes induced with aspirin and hypotonic (0.119 M) NaCl solution. An inhibiting effect was observed of low concentrations (2 X 10(-5) M, 2 X 10(-4) M and 2 X 10(-3) M) of aspirin on haemolysis induced with hypotonic NaCl solution, while in a concentration of 2 X 10(-2) M aspirin itself caused haemolysis which amounted to 93% of the haemolysis induced with 0.041 M NaCl solution. No differences were observed in the degree of haemolysis inhibition in relation to the time of incubation of erythrocytes with aspirin. Aspirin concentrations from 0.035 M to 0.280 M caused slight haemolysis (9-15% of the haemolysis induced with water), the 0.560 M solution caused haemolysis corresponding to 85% of the water-induced haemolysis. None of the studied prostaglandins used in concentrations of 0.4 X 10(-3) M, 0.4 X 10(-4) M and 0.4 X 10(-5) M had any significant effect on aspirin-induced haemolysis. PGE1 and PGE2 in concentrations of 0.4 X 10(-3) M, 0.4 X 10(-4) M and 0.4 X 10(-5) M inhibited haemolysis induced with 0.119 M sodium chloride solution, and the degree of haemolysis inhibition was from 8% to 35%. Prostaglandins PGF1 alpha and PGF2 alpha in the same concentrations had no protective effect.     

Oral PGE2 inhibits gastric acid secretion in man

The effect of oral prostaglandin E2 (PGE2) on gastric acid secretion was examined in healthy subjects. The gastric secretion was stimulated by a modified shamfeeding procedure. Each subject underwent one control test and three tests with intragastrically administered graded doses of PGE2: 0.5, 1.0 and 2.0 mg. Oral PGE2 significantly suppressed the peak and total acid response to vagal stimulation. The total acid output in controls was 27.5 +/- 3.2 mmol/90 min and 20.8 +/- 2.8, 15.8 +/- 2.2 (p less than 0.01) and 15.9 +/- 3.8 (p less than 0.005) mmol/90 min in test series with 0.5, 1.0 and 2.0 mg PGE2 respectively. The two higher doses were equally inhibitory to an average 40%. Gastric outputs of sodium and potassium in response to modified shamfeeding were reduced by PGE2. In controls there was a significant release of plasma-gastrin in response to shamfeeding. Plasma-gastrin was apparently suppressed after the two lower doses of PGE2 but 2.0 mg PGE2 gave an elevation similar to controls. Thus the study demonstrates that oral natural PGE2 suppresses the gastric acid secretion in man. The absence of such an effect in prior studies has been one of the objections against an acid regulatory action of endogenously formed prostaglandins. The present results do not support this argument.     

The effect of progesterone on oxytocin-stimulated intracellular mobilization of Ca2+ and prostaglandin E2 and F2alpha secretion from porcine myometrial cells

Our past studies have shown that porcine myometrium produce prostaglandins (PG) during luteolysis and early pregnancy and that oxytocin (OT) and its receptor (OTr) support myometrial secretion of prostaglandins E2 and F2alpha (PGE2 and PGF2alpha) during luteolysis. This study investigates the role of intracellular Ca2+ [Ca2+]i as a mediator of OT effects on PG secretion from isolated myometrial cells in the presence or absence of progesterone (P4). Basal [Ca2+]i was similar in myometrial cells from cyclic and pregnant pigs (days 14-16). OT (10(-7)M) increased [Ca2+]i in myometrial cells of cyclic and pregnant pigs, although this effect was delayed in myometrium from pregnant females. After pre-incubation of the myocytes with P4 (10(-5)M) the influence of OT on [Ca2+]i)was delayed during luteolysis and inhibited during pregnancy. Myometrial cells in culture produce more PGE2 than PGF2alpha regardless of reproductive state of the female. OT (10(-7)M) increased PGE2 secretion after 6 and 12 h incubation for the tissue harvested during luteolysis and after 12 h incubation when myometrium from gravid females was used. In the presence of P4 (10(-5)M), the stimulatory effect of OT on PG secretion was diminished. In conclusion: (1) porcine myometrial cells in culture secrete PG preferentially during early pregnancy and produce more PGE2 than PGF2alpha, (2) OT controls myometrial PGF2alpha secretion during luteolysis, (3) release of [Ca2+]i is associated with the influence of OT on PG secretion, and (4) the effects of OT on PG secretion and Ca2+ accumulation are delayed by P4 during luteolysis and completely inhibited by P4 during pregnancy.     

Stimulation by prostaglandin E2 of glucagon and insulin release from isolated rat pancreas.

To ascertain whether prostaglandins (PG) may play a role in the secretion of glucagon and in an attempt to elucidate the conflicting observations on the effects of PG on insulin release, the isolated intact rat pancreas was perfused with solutions containing 1.1 x 10(-9) to 1.8 x 10(-5)m PGE2. In the presence of 5.6 mM glucose significant increments in portal venous effluent levels of glucagon and insulin were observed in response to minimal concentrations of 2.8 X 10(-8) and 1.4 X 10(-7) PGE2, respectively; a dose-response relationship was evident for both hormones at higher concentrations of PGE2. When administered over 60 seconds, 1.4 X 10(-6)M PGE2 resulted in a significant increase in glucagon levels within 24 seconds and in insulin within 48 seconds. Ten-minute perfusions of 1.4 X 10(-6)M PGE2 elicited biphasic release of both islet hormones; Phase I glucagon release preceded that of insulin. Both phases of the biphasic glucagon and insulin release which occurred in response to 15-minute perfusions of 10 mM arginine were augmented by PGE2. These observations indicate that PGE2 can evoke glucagon and insulin release at concentrations close to those observed by others in the extracts of rat pancreas. We conclude that PG may be involved in the regulation of secretion of glucagon and insulin and may mediate and/or modify the pancreatic islet hormone response to other secretagogues.     

Prostaglandins and prostaglandin metabolites in human gastric juice

Human gastric juice contains higher concentrations of PG metabolites than of unmetabolized PG indicating that local metabolism might play a role in limiting the biological activity of PG in gastric mucosa and has to be considered when investigating endogenous gastric PG. A major fraction of the 15-keto-13,14-dihydro-PGE2 (KH2PGE2) formed in gastric mucosa and released into the gastric lumen seems to be rapidly dehydrated to a compound co-chromatographing with KH2PGA2, while the amounts of the bicyclic degradation product 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-PGE2 (11-deoxy-KH2-cyclo-PGE2), as measured by radioimmunoassay, in freshly extracted gastric juice are negligible. Stimulation of secretion with pentagastrin does not influence significantly the concentrations of PG and PG metabolites in human gastric juice, but total output tends to increase parallel to the increase in secretion volume. Levels of immunoreactive 6-keto-PGF1 alpha in human gastric juice are much lower than those of PGE2. Since human gastric mucosa synthesizes conciderable amounts of PGI2 and 6-keto-PGF1 alpha in vitro, the low levels of 6-keto-PGF1 alpha in gastric juice might indicate that PGI2 formed by gastric mucosa in vivo is, like PGE2 and PGF2 alpha, rapidly metabolized and/or removed preferentially via the blood stream.     

Effect of ionizing radiation on prostaglandins and gastric secretion in rhesus monkeys

Early radiation toxicity is characterized by nausea and vomiting. We have previously shown that gastric emptying, gastric motility, and gastric secretion were suppressed after total body exposure to irradiation. In the present studies, we evaluated the relation between vomiting and gastric function in nine rhesus monkeys and explored the possible role of prostaglandins (PG) in these phenomena. The concentration of PG in plasma and gastric juice was determined using a standard radioimmunoassay and gastric acid output was measured concurrently using a marker dilution technique. The animals were studied in the basal state and after total body exposure to 800 cGy 60Co delivered at a rate of 500 cGy/min. Acid output was abolished from 40 min to 2 h after irradiation but had returned to preirradiation levels 2 days later. Plasma PGE2 and PGI2 (as measured by 6-keto-PGF1 alpha determination) were not significantly modified by irradiation. In contrast, irradiation produced an immediate significant increase (P less than 0.05) in gastric juice concentration of PGE2 (318 +/- 80 to 523 +/- 94 pg/ml; mean +/- SE) and PGI2 (230 +/- 36 to 346 +/- 57 pg/ml); both had returned to basal levels 2 days later. Thus, an increase in gastric juice concentration of both PGE2 and PGI2 is associated with the radiation induced suppression of acid output.     

Role of prostaglandins in calcium-induced corticosteroid secretion by isolated frog interrenal gland

The role of prostaglandins (PGs) in calcium-induced corticosteroid secretion by frog adrenal (interrenal) gland has been examined in vitro using a perifusion technique. Increasing concentrations of CaCl2 (4-10 mM) stimulated in a dose-dependent manner aldosterone, PGE2 and 6-keto-PGF1 alpha production, whereas TXB2 was not affected. The kinetics of the adrenal response to CaCl2 indicated that the increase in PG output always preceded that of steroid. Administration of cobalt (4 mM), a calcium-channel inhibitor, blocked the calcium-induced stimulation of PGs and corticosteroids. Infusion of indomethacin (5 X 10(-6) M), a specific cyclooxygenase inhibitor, significantly decreased the basal production of PGs and steroids, and prevented the stimulatory effect of CaCl2 (6 mM). Infusion of the calcium ionophore A 23187 (10(-6) M), for 20 min, induced a marked stimulation of PG and steroid production. Taken together, these data support the notion that biosynthesis of prostaglandins is associated with calcium-induced corticosteroid secretion in frog adrenal cells.     

Early osmoregulatory stimulation of neurohypophyseal hormone secretion and thirst after gastric NaCl loads

Cerebral osmoreceptors mediate thirst and neurohypophyseal secretion stimulated by increases in the effective osmolality of plasma (P(osmol)). The present experiments determined whether an intragastric load of hypertonic saline (ig HS; 0.5 M NaCl, 4 ml) would potentiate these responses before induced increases in P(osmol) in the general circulation could be detected by cerebral osmoreceptors. Adult rats deprived of water overnight and then given intragastric HS consumed much more water in 15-30 min than rats given either pretreatment alone, even though systemic P(osmol) had not yet increased significantly because of the gastric load. In other rats pretreated with an intravenous infusion of 1 M NaCl (2 ml/h for 2 h), plasma levels of vasopressin and oxytocin were considerably elevated 15 and 25 min after intragastric HS treatment, whereas systemic P(osmol) was not increased further. These and other findings are consistent with previous reports that hepatic portal osmoreceptors (or Na(+) receptors) stimulate thirst and neurohypophyseal hormone secretion in euhydrated rats given gastric NaCl loads and indicate that these effects are potentiated when animals are dehydrated.     

Interactions of prostaglandins with subpopulations of ovine luteal cells. I. Stimulatory effects of prostaglandins E1, E2 and I2

Preparations of small and large steroidogenic cells from enzymatically dispersed ovine corpora lutea were utilized to study the in vitro effects of luteinizing hormone (LH) and prostaglandins (PG) E1, E2 and I2. Cells were allowed to attach to culture dishes overnight and were incubated with either LH (100 ng/ml), PGE1, PGE2, or PGI2 (250 ng/ml each). The secretion of progesterone by large cells was stimulated by all prostaglandins tested (P less than 0.05) while the moderate stimulation observed after LH treatment was attributable to contamination of the large cell population with small cells. Prostaglandins E1 and E2 had no effect on progesterone secretion by small cells, while LH was stimulatory at all times (0.5 to 4 hr) and PGI2 was stimulatory by 4 hr. Additional studies were conducted to determine if the effects of PGE2 upon steroidogenesis in large cells were correlated with stimulated activity of adenylate cyclase. In both plated and suspended cells PGE2 caused an increase (P less than 0.05) in the rate of progesterone secretion but had no effect upon the activity of adenylate cyclase or cAMP concentrations within cells or in the incubation media. Exposure of luteal cells to forskolin, a nonhormonal stimulator of adenylate cyclase, resulted in marked increases in all parameters of cyclase activity but had no effect on progesterone secretion. These data suggest that the actions of prostaglandins E1, E2 and I2 are directed primarily toward the large cells of the ovine corpus luteum and cast doubt upon the role of adenylate cyclase as the sole intermediary in regulation of progesterone secretion in this cell type.     

The role of cyclic nucleotides and prostaglandins in heart function.

A short review of the role of cyclic nucleotides and prostaglandins (PGs) in normal and pathological functions of the heart is given. Possible interrelationships of these two regulatory systems have been studied by using spontaneously beating rat atria preparations. Addition of noradrenaline (NA) to the incubate (1 . 10(-6) M) caused an increase in amplitude and frequency which was preceded and parallelled by an elevation of the tissue cAMP level. A transient increase in cGMP and PGE values was also seen. Propranolol (5 . 10(-6) M) abolished the increase in amplitude and frequency as well as in cAMP and PGE concentrations. Indomethacin (1 . 10(-5) M) inhibited the formation of PGE. The increase in cGMP was blocked by phenoxybenzamine. Interchange between beta- and alpha-receptors according as the temperature is lowered has been described earlier. Hypothermia (20 degrees C) had a positive inotropic effect on the atria and increased the tissue cAMP concentration. Loading of the atria caused an increase in cAMP without any effects on cGMP or PGs. Slight hypoxia did not change the cAMP or PG levels, but elevated the cGMP values. Arrhythmias induced by hypo- or hyperpotassemia did not modify the biochemical parameters measured. PGF2alpha (1. 10(-5) M) normalized the atrial rhythm and increased the amplitude without changing cyclic nucleotide or PG levels. PGE1 (1 . 10(-4) M) increased the amplitude of normorhythmic atria and the tissue concentration of cAMP. PGE2 was the only PG tested which stimulated the heart adenylate cyclase in vitro. There seems to be close but complicated relationships between cyclic nucleotides and PGs in the heart.     

Involvement of prostaglandins in the response of frog adrenocortical cells to muscarinic receptor activation

The role of prostaglandins (PGs) in the mechanism of action of acetylcholine (ACh) on frog adrenocortical cells has been examined. Administration of a single dose of ACh (5 X 10(-5) M) to perifused frog interrenal fragments, for 20 min, stimulated the production of corticosterone, aldosterone, PGE2 and 6-keto-PGF1 alpha. In contrast ACh did not significantly alter TXB2 production. The effect of ACh could be mimicked by muscarine (10(-5) M). Conversely, nicotine (10(-6) to 10(-4) M) was totally inactive. The increase in PG biosynthesis preceded the peak of corticosteroid release. Repeated 20-min pulses of ACh (5 X 10(-5) M) or muscarine (10(-5) M) given at 130-min intervals induced a desensitization phenomenon. In presence of indomethacin (5 X 10(-6) M), the effect of ACh on PG and steroid secretion was totally abolished. In calcium-free medium, the effect of ACh on PG and corticosteroid production was completely blocked. These results indicate that, in the frog, ACh stimulates corticosteroid secretion through a PG-dependent mechanism.     

Comparative gastric antisecretory and antiulcer effects of prostaglandin E1 and its methyl ester in animals.

The influence of methyl esterification of the carboxyl group of PGE1 on the gastric antisecretory and antiulcer activities were studied. The gastric antisecretory effects of PGE1 free acid and PGE1 methyl ester (PGE1ME) were studied in the Heidenhain pouch dog. Secretion was stimulated with constant intravenous infusion of histamine dihydrochloride. When a steady-state plateau of gastric secretion had been reached, the prostaglandins were administered either by a single intravenous bolus (10.0 mug/kg) or by continuous infusion (1.0 mug/kg/min). PGE1ME was found to be slightly more potent and longer-acting than PFE1 when administered by a single i.v. bolus. PGE1ME was also shown to be more potent than PGE1 when infused intravenously for a two-hour period. PGE1ME caused a significant alteration in gastric juice concentration of hydrogen and sodium ions in an inverse relationship. Potassium and chloride concentration were not altered from pre-existing steady-state values following administration of either form of prostaglandin. Similarly, PGE1ME was also found to possess significantly greater antiulcer activity in the rat forced-exertion ulcer test. These findings support the hypothesis that methyl esterification of the prostaglandin molecule will increase some of the biological actions of PGE1 through inhibition of metabolic beta-oxidation of the carboxylic side chain.     

Adrenomedullin promotes epithelial restitution of rat and human gastric mucosa in vitro

We have investigated the effect of adrenomedullin (AM) on restitution of mucosal integrity following damage in rat and human gastric mucosa, measuring the potential difference (PD) on a mucosal strip mounted on an Ussing chamber. Mucosal damage was induced by 0.5, 1.0, and 2.0 M NaCl solution, and it caused an immediate and significant decrease in PD. In the rat AM group, PD recovered significantly more than in control group at 120 min after exposure to 0.5 M (p < 0.01) and 1.0 M (p < 0.05) NaCl solution. In the human AM group, PD completely recovered at 120 min after exposure to 0.5 M (p < 0.05) NaCl solution. In rat mucosa damaged by 0.5 M NaCl solution, the effect was inhibited by human (h)-CGRP(8-37) and there was no significant difference between the h-CGRP(8-37) group and control group. On immunohistochemical examination of rat gastric mucosa, AM was detected within the chief cell. AM probably promotes epithelial restitution primarily through the CGRP receptor, but it does not ameliorate more severe damage of gastric mucosa in vitro.     

Prostaglandins may not mediate inhibition of gastric acid secretion by somatostatin in the rat

The role of prostaglandins as mediators of the inhibitory effect of somatostatin on gastric acid secretion has been evaluated in conscious and anesthetized rats. The effect of somatostatin on bethanechol-stimulated gastric acid secretion was determined with or without indomethacin pretreatment. Prostaglandin synthesis inhibition (less than 90%) by indomethacin was verified with PGE2-generation assay on gastric mucosal tissue. In both conscious and anesthetized rats somatostatin significantly inhibited the stimulated acid output in the control and indomethacin pretreated groups. The present findings do not support a role for prostaglandins in the inhibition of gastric acid secretion by somatostatin in the rat.     

Relation of prostaglandin-induced increases in cellular cAMP to stimulation of pepsinogen secretion from dispersed chief cells

The actions of prostaglandins (PG) on cAMP in dispersed chief cells from guinea pig stomach were examined and compared to the actions of these agents on pepsinogen secretion. Maximal concentrations of A, B, or E prostaglandins caused a 2-5-fold increase in pepsinogen secretion and cellular cAMP. The relative order of potency for these actions was PGEs greater than PGAs greater than PGBs. Detection of prostaglandin-induced changes in cAMP was enhanced by adding a phosphodiesterase inhibitor to the incubation solution. The time courses for the effects of prostaglandins on pepsinogen secretion and cAMP were similar. With PGE1 an increase in cAMP and pepsinogen secretion was detected by 1 min and was maximal by 7.5 min. Although significant increases in cAMP were detected with a ten-fold lower concentration of PGEs than PGAs, a maximal increase in cAMP was observed with the same concentration, 30 microM, of either agent. These data indicate that prostaglandins that stimulate pepsinogen secretion increase cAMP in dispersed chief cells. However, comparison of the dose-response curves for the actions of prostaglandins on pepsinogen secretion and cAMP revealed that detectable increases in cAMP occurred with concentrations of these agents that were about ten-fold greater than those needed to stimulate pepsinogen secretion. Therefore, although the similarity in the kinetics and relative potencies of prostaglandin-induced changes in cAMP and enzyme secretion provides further evidence that changes in cAMP play a role in the mediation of prostaglandin-induced pepsinogen secretion, the present data suggest the involvement of a cellular messenger in addition to cAMP.     

Inhibitory effects of PGE1 on glucose induced insulin release in isolated islets of Langerhans

Since prostaglandins are increasingly shown to play an important role on insulin secretion, an evaluation of the PGE1 action on insulin release by isolated islets of Langerhans has been undertaken. Pancreatic islets were prepared after a modification of the Lacy and Kostianovsky technique and incubated in Hanks solution containing glucose 1.63 or 16.3 mM and/or PGE1 10(-5) M. The insulin released was measured after 15, 30 or 60 min of incubation. The results obtained show that PGE1 does not modify insulin release induced by glucose 1.63 mM (non stimulant concentration) but that this PG significantly diminishes the insulin release induced by glucose 16.3 mM (stimulant concentration) after 15 and 30 min of incubation.     

The key-role of vagal nerve and adrenals in the cytoprotection and general gastric mucosal integrity.

BACKGROUND: Our laboratory group observed earlier that the gastric mucosal cytoprotective effect of prostacyclin (PGI(2)) disappeared after surgical vagotomy in rats. Similarly to this, the beta-carotene induced gastric cytoprotection disappeared in adrenalectomized rats too. AIMS: In these studies we aimed to investigate the possible role of vagal nerve and adrenals in the development of gastric mucosal lesions induced by exogenously administered chemicals (ethanol, HCl, NaOH, NaCl and indomethacin), and on the effects of cytoprotective and antisecretory drugs (atropine, cimetidine), and scavengers (vitamin A and beta-carotene). METHODS: The observations were carried out in fasted CFY strain rats. The gastric mucosal lesions were produced by intragastric (i.g.) administration of narcotising agents (96% ethanol; 0.6 M HCl; 0.2 M NaOH; 25% NaCl) or subcutaneously (s.c.) administered indomethacin (20 mg/kg) in intact, surgically bilaterally vagatomized, and adrenalectomized rats without or with glucocorticoid supplementation (Oradexon, 0.6 mg/kg given i.m. for 1 week). The gastric mucosal protective effect of antisecretory doses of atropine (0.1-0.5-1.0 mg/kg i.g.) and cimetidine (10-25-50 mg/kg i.g.), and vitamin A and beta-carotene (0.01-0.1-1.0-10 mg/kg i.g.) was studied. The number and severity of mucosal gastric lesions was numerically or semiquantitatively measured. In other series of observations the gastric acid secretion and mucosal damage were studied in 24 h pylorus-ligated rats without and with acute bilateral surgical vagotomy. RESULTS: It was found that: (1) the chemical-induced gastric mucosal damage was enhanced in vagotomized and adrenalectomized rats, meanwhile the endogenous secretion of gastric acid, and the development of mucosal damage can be prevented by surgical vagotomy; (2) the gastric cyto- and general protection produced by the drugs and scavengers disappeared in vagotomized and adrenalectomized rats; (3) the gastric mucosal protective effects of drugs and of scavengers returned after sufficient glucocorticoid supplementation of the rats. CONCLUSION: It has been concluded that the intact vagal nerve and adrenals have a key role in the gastric mucosal integrity, and in drugs- and scavengers-induced gastric cyto- and general mucosal protection.     

Effect of prostaglandins on hypothalamic-pituitary-testicular function in vitro.

The effect of prostaglandins (PG) A1, E1, E2 and F2 alpha in the concentration range of 10(-7)--10(-4) M were studied in vitro on a rat hypothalamic tissue, collagenase-digested isolated anterior pituitary cell and Leydig cell suspension system by measuring the testosterone production of incubated Leydig cells. PGs did not change the testosterone production and the hCG sensitivity of the Leydig cells, nor the LH secretion and the LHRH sensitivity of the anterior pituitary cells. PGE2 at concentrations of 10(-6), 10(-5) and 10(-4) M significantly increased the hypothalamic tissue-induced pituitary-testicular activation, and this stimulatory effect of PGE2 was dose dependent. PGA1, PGE1 and PGF2 alpha did not alter hypothalamic LHRH release measured in vitro. The results suggest that PGE2 has a direct stimulatory effect on hypothalamic LHRH release.     

The urinary excretion of prostaglandins and thromboxane B2 in healthy volunteers: a study in males and females, and on the influence of seminal fluid contamination

Radioimmunoassay measurements of prostaglandins (PGs) E2, F2 alpha, 6-keto-PGF1 alpha and thromboxane (Tx) B2 in 24 h urine specimens from a male and a female healthy volunteer on several consecutive days revealed a dramatic increase of PGE2, PGF2 alpha, 6-keto-PGF1 alpha on days, upon which they had sexual intercourse; only TxB2 remained stable. Furthermore, the PGE2/PGF2 alpha ratio rose to values greater than 0.5 on days with sexual intercourse. This was found to be due to contamination of the urine samples by seminal fluid. Two 24 h urine samples from each of 26 healthy male and female volunteers (HV) revealed higher (p less than 0.01) mean PGE2 and PGF2 alpha values in males than in females. The results show that the interpretation of the urinary PG excretion as a measure of renal PG synthesis should be considered carefully, and that a PGE2/PGF2 alpha ratio greater than 0.5 indicates probable seminal contamination of urine.