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.     

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.     

Synthesis of thromboxane B2 and 6-keto-prostaglandin F1α by bovine gastric mucosal and muscle microsomes

Bovine gastric mucosal and muscle microsomes synthesize prostaglandins and thromboxane B₂ (TXB₂) from arachidonic acid (AA). TXB₂ and 6-keto-prostaglandin F₁α (6-keto-PGF₁α) were the major products synthesized by pylorus, body, and cardiac region of the gastric mucosa. Gastric muscle mainly synthesized 6-keto-PGF₁α. TXB₂ and 6-keto-PGF₁α synthesis occurs at an appreciable rate from endogenous precursors but more rapidly with added arachidonate. Prostaglandins E₂, F₂α and D₂ were synthesized in smaller amounts under the conditions studied.     

Comparison of umbilical vein models for measurement of relative prostacyclin and thromboxane production

There is growing evidence that blood vessels generate TXA₂ in addition to PGI₂. We examined effluents from continously perfused human umbilical vein and supernatants from umbilical vein rings for TXB₂ and 6-keto-PGF_1α measurements (stable metabolites of TXA₂ and PGI₂, respectively). TXB₂ and 6-keto-PGF_1α were identified in all samples. 6-keto-PGF_1α to TXB₂ ratio was higher in intact vein effluents than in the venous ring supernatants (112:1 and 28:1, respectively, P<0.01). Arachidonate stimulation increased 6-keto-PGF_1α and TXB₂ levels similarly in the intact vein effluent. In contrast, stimulation of the venous rings resulted in a relatively larger increase in TXB₂ than in 6-keto-PGF_1α. This caused 6-keto-PGF_1α to TXB₂ ratio to decline (p<0.01). The identity of TXB₂ was confirmed in several different ways. These data suggest that 1) human umbilical veins produce TXA₂ in addition to PGI₂, 2) TXA₂ release is more by venous rings than by the intact vein probably reflecting contribution from non-endothelial layers, and 3) arachidonate stimulation causes relatively greater release of TXA₂ than of PGI₂ from the venous rings, whereas release of PGI₂ and TXA₂ is similar from the intact vein.     

Effects of nitrogen dioxide exposure on the contents of prostaglandins and thromboxane B2 in broncho alveolar lavage

Effects of 10 ppm nitrogen dioxide (NO₂) exposure on the contents of prostaglandins (PGs) and thromboxane (TX) B₂ in broncho-alveolar lavage (BAL) of rats were studied. In the BAL of normal rats, the amounts of PGs and TXB₂ in the whole lavage were 6-keto-PGF_1α (38.0 ± 6.4 ng) > TXB₂ (11.8 ± 4.0 ng) > PGF_2α (5.7 ± 1.6 ng) PGE (0.5 ± 0.3 ng). Rats were exposed to NO₂ for 1, 3, 5, 7 and 14 days. The NO₂ exposure decreased in the level of 6-keto-PGF_1α by about 35% throughout the exposure. The level of TXB₂ was higher in the day 5 exposure group (155%). The contents of PGF_2α and PGE first, decreased and then transiently increased on days 3 and 5. PG 15-hydroxy-dehydrogenase activity of lung homogenate decreased correspondingly on day 3 and 5. Then the contents PGF_2α and PGE decreased on day 7 and 14.6-keto-PGF_1α and TXB₂ are stable metabolites of PGI₂, a strong bronchorelaxant and TXA₂, a strong bronchoconstrictor respectively. Therefore the results suggested that the decrease in 6-keto-PGF_1α, a major prostanoid in the BAL and the increase in TXB₂ may correlate with broncho constriction by NO₂ exposure.     

Prostanoids and hemodynamics in man before and during cardiopulmonary bypass

The plasma concentration of 6-keto-PGF_1α, the stable degradation product of prostacyclin, was similar in the radial and pulmonary arteries and in the coronary sinus before and after the induction of the anesthesia in patients undergoing coronary artery bypass surgery. After the beginning of the mechanical ventilation and anesthesia the pulmonary vascular resistance decreased although no changes were detected in the plasma levels of 6-keto-PGF_1α or TXB₂. During the prebypass period after the sternotomy and cannulation of the large vessels the plasma level of 6-keto-PGF_1α was increased similarly in the radial and pulmonary arteries and even more in the coronary sinus. During the cardiopulmonary bypass the concentration of 6-keto-PGF_1α remained at the increased level as compared to the values before the anesthesia. This indicates that pulmonary circulation is perhaps not the main source of prostacyclin in man. The plasma level of TXB₂ was increased during the prebypass period significantly only in the coronary sinus, but during the bypass also in the radial artery. The concentration ratio of 6-keto-PGF_1α/TXB₂ was increased significantly during the prebypass period in the radial and pulmonary arteries. At the same time the pulmonary vascular resistance was, however, returned to the preanesthesia level and was thus not decreased. The vascular resistance in the systemic circulation was increased during the prebypass period. The plasma level of 6-keto-PGF_1α or TXB₂ in the radial and pulmonary arteries did not correlate significantly with the total vascular resistance in the systemic and pulmonary circulation, respectively. The vascular resistance in the coronary circulation did not correlate significantly with TXB₂ level in the radial artery or coronary sinus. There was, however, a slight positive correlation between the blood flow and the concentration of TXB₂ in the coronary sinus (r=0.76, P < 0.01). Coronary sinus flow did, however, not correlate with the plasma level of 6-keto-PGF_1α in the radial artery or coronary sinus. These results indicate that the detected plasma concentrations of prostacyclin and thromboxane A₂ have no significant effects on the total vascular resistance in vivo.     

Oxytocin-stimulated production of prostaglandin F2α by isolated endometrium of rabbit: Modulation by ovarian steroids

To test the hypothesis that ovarian steroid hormones modulate oxytocin-induced release of prostaglandin F_2α (PGF_2α) from uterine endometrium, 2 ovariectomized rabbits were pretreated with progesterone (5 mg/day for 10 days), 2 with estradiol-17β (25 μg/day for 10 days), 2 with both steroids, and one with sesame oil only. On the last day of treatment, endometrial fragments were excised and incubated in vitro with or without oxytocin (100 μU/ml). Although endometrium from rabbits pretreated with combined steroids released more PGF_2α immediately after excision than did tissue from animals pretreated with either steroid by itself, endometrium from animals pretreated with estrabdiol-17β alone released the most PGF_2α during sustained incubation in vitro. Moreover, only this tissue exhibited significant oxytocin-dependent release of PGF_2α. At the dosages used, progesterone completely antagonized both of these effects of estradiol-17β. The results support the hypothesis that ovarian steroid hormones regulate oxytocindependent release of PGF_2α from endometrial cells. A possible mechanism of action is suggested.     

Determination of 6-keto-PGF1α, 2,3-dinor-6-keto-PGF1α, thromboxane B2, 2,3-dinor-thromboxane B2, PGE2, PGD2 and PGF2α in human urine by gas chromatography—negative ion chemical ionization mass spectrometry

A method for quantification of 6-keto-PGF_1α, 2,3-dinor-6-keto-PGF_1α, TXB₂, 2,3-dinor TXB₂, PGE₂, PGD₂ and PGF_2α in human urine samples, using gas chromatography—negative ion chemical ionization mass spectrometry, is described. Deuterated analogues were used as internal standards. Methoximation was carried out in urine samples which were subsequently applied to phenylboronic acid cartridges, reversed-phase cartridges and thin-layer chromatography. The eluents were further derivatized to pentafluorobenzyl ester trimethylsilyl ethers for final quantification by gas chromatography—mass spectrometry. The overall recovery was 77% for tritiated 6-keto-PGF_1α and 55% for tritiated TXB₂. Urinary levels of prostanoids were determined in a group of six volunteers before and after intake of the thromboxane synthase inhibitor Ridogrel, and related to creatinine clearance.     

Estrogen increases male rat aortic endothelial cell (RAEC) PGI2 release

Estrogen has been proposed as a negative risk factor for development of peripheral vascular disease yet mechanisms of this protection are not known. This study examines the hypothesis that estrogen stimulates rat aortic endothelial cell (RAEC) release of PGI₂. Male Sprague-Dawley rat abdominal aortic 1-mm rings were placed on 35 mm matrigel plates, and incubated for 1 week. The cells were transferred to a Primaria 60-mm dish and maintained from passage 3 in RAEC complete media and experiments performed between passages 4–10. Cells were incubated with Krebs-Henseleit buffer (pH 7.4) containing carrier or increasing concentrations of β-estradiol or testosterone for 60 min. The effluent was analyzed for eicosanoid release of 6-keto-PGF_1α (6-keto, PGI₂ metabolite), PGE₂ and thromboxane B₂ (TXB₂) by EIA (hormone stimulated — basal). Cells were analyzed for total protein by the Bradford method and for cyclooxygenase-1 (COX-1) and prostacyclin synthase (PS) content by Western blot analysis and densitometry. Testosterone did not alter RAEC 6-keto-PGF_1α release, whereas estrogen increased RAEC 6-keto-PGF_1α release in a dose-related manner. Estrogen preincubation (10 ng/ml) decreased COX-1 and PS content by 40% suggesting that the estrogen-induced increase in male RAEC PGI₂ release was not due to increased synthesis of COX-1 or PS. These data support the hypothesis that estrogen stimulation can increase endogenous male RAEC release of PGI₂.     

Effects of Danshensu on Platelet Aggregation and Thrombosis: In Vivo Arteriovenous Shunt and Venous Thrombosis Models in Rats

Danshensu, a type of dihydroxyphenyl lactic acid, is one of the most abundant active phenolic acids in the dried root of Salvia miltiorrhizae (Lamiaceae)—widely used traditional Chinese medicine. The effects of danshensu on platelet aggregation and thrombus formation in rats were examined using various methods. It was found that danshensu significantly reduced thrombus weight in 2 experimental thrombosis models; dose-dependent inhibition of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation occurred in normal and blood stasis-induced rats; Danshensu also significantly mitigated blood viscosity, plasma viscosity and hematocrit levels. Moreover, danshensu significantly inhibited venous thrombosis-induced expression of cyclooxygenases-2 (COX-2) rather than cyclooxygenases-1(COX-1) in the venous walls, down regulated thromboxane B₂ (TXB₂) and up regulated 6-keto prostaglandin F_1α (6-keto-PGF_1α), normalizing the TXB₂/6-keto-PGF_1α ratio. In addition, danshensu did not induce gastric lesions and even had protective effects on aspirin-induced ulcer formation at doses as high as 60 mg/kg. These findings suggest that the antithrombotic and antiplatelet aggregation effects of danshensu are attributed to its highly selective inhibition of COX-2 and ability to normalize the thromboxane A₂(TXA₂)/prostacyclin(PGI₂) balance. These findings suggest that danshensu have great prospects in antithrombotic and antiplatelet therapy.     

Retinoblastoma protein promotes uterine epithelial cell cycle arrest and necroptosis for embryo invasion

Retinoblastoma protein (RB) encoded by Rb1 is a prominent inducer of cell cycle arrest (CCA). The hormone progesterone (P₄) promotes CCA in the uterine epithelium and previous studies indicated that P₄ activates RB by reducing the phosphorylated, inactive form of RB. Here, we show that embryo implantation is impaired in uterine‐specific Rb1 knockout mice. We observe persistent cell proliferation of the Rb1‐deficient uterine epithelium until embryo attachment, loss of epithelial necroptosis, and trophoblast phagocytosis, which correlates with subsequent embryo invasion failure, indicating that Rb1‐induced CCA and necroptosis of uterine epithelium are involved in embryo invasion. Pre‐implantation P₄ supplementation is sufficient to restore these defects and embryo invasion. In Rb1‐deficient uterine epithelial cells, TNFα‐primed necroptosis is impaired, which is rescued by the treatment with a CCA inducer thymidine or P₄ through the upregulation of TNF receptor type 2. TNFα is expressed in the luminal epithelium and the embryo at the embryo attachment site. These results provide evidence that uterine Rb1‐induced CCA is involved in TNFα‐primed epithelial necroptosis at the implantation site for successful embryo invasion.     

Formation of prostanoids in human umbilical vessels perfused

Four major prostanoids (6-keto-PGF_1α, PGE₂, PGF_2α and TXB₂) were measured by specific radioimmunoassays in the outputs from human umbilical vessels perfussed . As evaluated by scanning electron microscopy (SEM) only few blood platelets were attached to the vessel wall. After an initial flush with decreasing concentrations of all four prostanoids, a stable stage was reached, lasting for 4–5 hours. During this stage the production could be inhibited by indomethacin and only slightly stimulated with arachidonic acid. The TXA₂ synthetase inhibitor UK 38485 depressed the TXB₂ production, while only slightly affecting the other three prostanoids at very high concentrations. The arteries produced relatively more 6-keto-PGF_1α than did the vein.     

Major urinary metabolites of 6-keto-prostaglandin F2α in mice

Western diets are enriched in omega-6 vs. omega-3 fatty acids, and a shift in this balance toward omega-3 fatty acids may have health benefits. There is limited information about the catabolism of 3-series prostaglandins (PG) formed from eicosapentaenoic acid (EPA), a fish oil omega-3 fatty acid that becomes elevated in tissues following fish oil consumption. Quantification of appropriate urinary 3-series PG metabolites could be used for noninvasive measurement of omega-3 fatty acid tone. Here we describe the preparation of tritium- and deuterium-labeled 6-keto-PGF_2α and their use in identifying urinary metabolites in mice using LC-MS/MS. The major 6-keto-PGF_2α urinary metabolites included dinor-6-keto-PGF_2α (∼10%) and dinor-13,14-dihydro-6,15-diketo-PGF_1α (∼10%). These metabolites can arise only from the enzymatic conversion of EPA to the 3-series PGH endoperoxide by cyclooxygenases, then PGI₃ by prostacyclin synthase and, finally, nonenzymatic hydrolysis to 6-keto-PGF_2α. The 6-keto-PGF derivatives are not formed by free radical mechanisms that generate isoprostanes, and thus, these metabolites provide an unbiased marker for utilization of EPA by cyclooxygenases.     

Plasma prostaglandin levels and circulating fuel levels in rats with diabetic ketoacidosis: Effects of cyclooxygenase inhibitors and of alpha and beta adrenergic blockade

We studied the effects of two structurally unrelated inhibitors of the fatty acid cyclooxygenase and of alpha and beta adrenergic blockade on the elevated plasma levels of 13,14-dihydro-15-keto-prostaglandin (PG)E₂, 6-keto-PGF_1α and thromboxane(TX)B₂, the stable derivatives of PGE₂, PGI₂ (prostacyclin) and TXA₂, respectively, in rats with streptozotocin-induced diabetic ketoacidosis (DKA). Meclofenamic acid and indomethacin each produced a significant decrease in the elevated plasma levels of 13,14-dihydro-15-keto-PGE₂, 6-keto-PGF_1α and TXB₂. Phentolamine significantly reduced the plasma level of TXB₂ but had no effect on the elevated circulating levels of glucose, free fatty acids, total ketones, 13,14,-dihydro-15-keto-PGE₂ or 6-keto-PGF_1α. Propranolol significantly reduced the elevated circulating levels of glucose, free fatty acids and total ketones but had no effect on the levels of the three prostaglandin derivatives. The ability of meclofenamic acid and indomethacin to reduce the plasma levels of 13,14-dihydro-15-keto-PGE₂, 6-keto-PGF_1α and TXB₂ confirms that the plasma levels of these three derivatives are elevated in rats with DKA. Since abnormalities in the production of PGI₂ and perhaps other cyclooxygenase derivatives may contribute to the pathogenesis of certain important hemodynamic and gastrointestinal features of DKA, cyclooxygenase inhibitors may play a role in the management of selected patients with this disorder. Alpha adrenergic activity is essential for the maintenance of the elevated plasma TXB₂ level in rats with DKA. The fall in the plasma TXB₂ level during alpha adrenergic blockade appears to reflect inhibition of platelet aggregation and platelet TXA₂ production, but other sources of the elevated plasma TXB₂ level in DKA are not excluded. Beta adrenergic activity contributes to the maintenance of elevated circulating levels of glucose, free fatty acids and total ketones in experimental DKA but not to the elevated plasma levels of the prostaglandin derivatives.     

Changes in urinary 6-keto-prostaglandin F1α excretion during pregnancy and labor

Urinary excretion of 6-keto-PGF_1α was measured by high pressure liquid chromatography and radioimmunoassay at various stages of pregnancy and labor. In the first trimester of pregnancy, urinary 6-keto-PGF_1α concentrations were nor different from those measured before pregnancy, but they showed a significant increase in the second trimester of pregnancy (p <0.001). The levels rose further in the third trimester, although this increase was not statistically significant when compared to levels obtained in the second trimester. There was no evidence for a significance change in 6-keto-PGF_1α excretion with the onset of labor. During well-established, progressive labor mean values of 6-keto-PGF_1α excretion were about twice as high as before the onset of labor, but the range of values during labor was so wide that there was no statistical difference with values obtained in the second half of pregnancy.It is concluded that the increase in the urinary excretion of 6-keto-PGF_1α occurs later in pregnancy than the increase in TXB₂ excretion and that labor at term is not associated with marked changes in 6-keto-PGF_1α excretion.     

Phorbol myristate acetate-stimulated release of cyclooxygenase products in rat pleural cells: Derivatization of prostaglandins with 9-anthryldiazomethane for fluorometric determination by high performance liquid chromatography

White cells were collected from the wash of rat pleural cavity after exsanguination. The incubation mixture of the pleural cells with 1 μM phorbol myristate acetate (PMA) was extracted with acidified ethanol and purified with a Sep-pak C18. The resultant fraction containing prostaglandins (PG) and thromboxane (TX) was allowed to react with 9-anthryldiazomethane (ADAM). After removing contaminants and degraded reagent by silica gel Sep-pak, samples were applied to reversed phase high performance liquid chromatography of octadecylsilyl silica gel and monitored by a fluorescent detector. ADAM derivatives of the authentic PGD₂, PGE₂, PGF_2α, 6-keto-PGF_1α, 6-keto-PGE₁, TXB₂, 15-keo-PGE₂, 13, 14-dihydro-15-keto-PGF_2α and 13, 14-dihydro-15-keto-PGE₂ showed linear regression lines of peak heights within a range of 0.5–25 ng.By using this method PGD₂, 6-keto-PGF_1α and TXB₂ were detected in the incubation mixture of the rat pleural cells with PMA. The result clarified the origin of these PGs and TX found in the exudate of rat pleurisy induced by PMA.ADAM method for HPLC with a help of clean-up by Sep-pak could be a useful tool for detection of a series of arachidonate metabolites in biological materials.     

Relationship between prostaglandin in peritoneal fluid and pelvic venous congestion after sterilization

Pelvic congestion may cause chronic pelvic pain in women. The aim of the study is to elucidate a possible role in this condition for prostaglandin. Prostaglandin levels in peritoneal fluid were measured in 18 women with pelvic pain caused by pelvic congestion following sterilization, 10 women without pain following sterilization, and 10 normal healthy women. Peritoneal fluid was aspirated by a silastic catheter from the cul-de-sac under laparoscopic direct vision. Concentration of 6-keto-PGF_1α, TXB₂, PGF_2α and PGE₂ were measured with the standard radioimmunoassay method in all samples. Results showed that 6-keto-PGF,. levels in peritoneal fluid from patients with pelvic congestion were markedly higher than those from two control women (P < 0.05); 6-keto-PGF_1α/TXB₂ in pelvic congestion and control groups were markedly different (P < 0.05); the total amounts of peritoneal fluid was higher in pelvic congestion than that in two control groups (P < 0.001). These data suggested that 6-ketoPGF_1α is increased in peritoneal fluid of women with pelvic congestion and the change might play an important role in attack of this disease.     

Effects of oestradiol, progesterone, hydrocortisone and oxytocin on prostaglandin output from the guinea-pig endometrium maintained in tissue culture

The effects of oestradiol, oxytocin, progesterone and hydrocortisone on prostaglandin (PG) output from guinea-pig endomerium, removed on days 7 and 15 of the oestrous cycle and maintained in tissue culture for 3 days, have been investigated. Oetradiol (3.7 to 3700nM) and oxytocin ( 2 to 200pM) did not stimulate endometrial PGF_2α output, thus not confirming the findings of a previous report (Leaver & Seawright, 1928), nor did they stimulate the outputs of PGE₂ and 6-keto-PGF_1α. In fact, oestradiol (3700nM) inhibited the outputs of PGF_2α, PGE₂ and, to a lesser extent, 6-keto-PGF_1α. Progesterone (3.2 to 3200nM) inhibited the outputsof PGF_2α and PGE₂; hydrocortisone (2.8 to 2800nM) had no effect on endometrial PG output. These findings indicate that the inhibitory effect of progesterone on endometrial PG synthesis and release in the guinea-pig is not due to progesterone having a glucocorticoid-like action. Furthermore, progesterone had no effect on 6-keto-PGF_1α output, suggesting that the mechanisms controlling endometrial PGI₂ synthesis (as reflected by measuring 6-keto-PGF_1α) are different from those controlling endometrial PGF_2α and PGE₂ synthesis.     

Effects of experimental diabetes on spontaneous contractions, on the output of prostaglandins and on the metabolism of labelled arachidonic acid, in uteri isolated from ovariectomized rats. Influences of estradiol

Spontaneous changes in isometric developed tension (IDT) as a function of time after isolation (contractile constancy) in uteri from control-castrated and castrated chronic streptozotocin-diabetic rats, were explored. The effects of injecting 17-beta estradiol (E₀) were also studied. No differences in the minor changes of contractile constancy, between control and diabetic preparations, during a period of 60 min, were detected, whereas uteri from non-diabetic E_O injected animals (0.5+1.0 ug, prior to sacrifice), exhibited a profound reduction of IDT, significantly greater than in tissues obtained from E₀ injected-diabetic rats. Moreover, basal generation and outputs into the suspending solution of prostaglandins (PGs) E₁, E₂ and F_2α, were explored in the same groups, at 60 min following tissue isolation. The basal outputs of these three PGs were similar in castrated control rats, but preparations from castrated-diabetics released significantly more PGE₁. The administration of E₀ to castrated-diabetics, failed to alter the releases of the three PGs explored. In addition, the metabolism of labelled arachidonic acid (AA) into different prostanoids (6-keto-PGF₁, PGF₂, PGE₂ and thromboxane B₂-TXB₂), was also investigated. The non-diabetic spayed rat uterus converted AA into these four prostanoids, the transformation into 6-keto-PGF₁α (as an index of PGI₂ formation) being the most prominent. In preparations from diabetic rats the formation) being the most prominent. In preparations from diabetic rats the formation of 6-keto-PGF₁α, PGF₂α and PGE₂, was significantly smaller than in controls, whereas a greater % of TXB₂ formation (as an index of TXA₂), was detected. On the other hand uterine preparations from non-diabetic spayed rats injected with E₀ formed less 6-

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amounts of PGF₂α or of TXB₂ from AA, than E₀ injected controls, whereas uteri from castrated diabetic animals injected with E₀, formed a similar % of 6-keto-PGF₁α, PGF₂α and PGE₂ from AA, than tissue preparations from non-estrogenized controls. However, the enhanced transformation of the labelled fatty acid precursor (AA) into TXB₂ in the diabetic group, was significantly reduced by the steroid. The role of the augmented generation and release of PGE₁ in uteri from diabetic rats is discussed in terms of precedents indicating the relevance of PGs type E supporting rat uterine motility. In addition the influence of E₀ is attractive, because its reducing effect on TX production, in diabetes, a disease known to be accompanied by enhanced synthesis of vasoconstrictor and platelet aggregation TXA₂, and by frequent obstructive circulatory problems.