The measurement of human endometrial prostaglandin production a comparison of two in vitro methods

Two $\text{in vitro}$ methods for measuring human endometrial prostaglandin production were compared. Endometrial samples from eight patients were incubated over eight hours by a perifusion and a superfusion technique. The collected fractions were assayed by radioimmunoassay for PGE₂ and PGF_2α.There was no significant difference between the perifusion and superfusion methods for the pattern and amount of PGE₂ and PGF₂ production with time. Significantly higher production levels of PGE₂ and PGF_2α were found in secretory phase endometria than in proliferative phase endometria. Histological examination of the tissue specimens by light and electron microscopy showed that both methods caused gross tissue damage after eight hours experimentation. The superfusion method produced more morphological damage than the perifusion method. However, no tissue damage could be detected after one hour of incubation with either method.Over an eight hour period neither the perifusion nor the superfusion technique appears to be a good indicator of $\text{in vivo}$ endometrial prostaglandin production. Either reflect the $\text{in vitro}$ situation.     

Prostaglandin secretion by perifused bovine endometrium: secretion towards the myometrial and luminal sides at day 17 post-estrus as altered by pregnancy

Bilateral perifusion devices were utilized to measure prostaglandin secretion towards luminal and myometrial sides of bovine endometria. Tissues were collected at Day 17 post-estrus from cyclic (n = 4), pregnant (n = 5) and bred but subsequently non-pregnant (n = 6) cows. Tissue from each cow was placed into two perifusion devices, perifused with Krebs-Ringer Bicarbonate solution (3 ml/10 min) for 2.5 h and fractions collected every 10 min. Oxytocin (1 IU/ml) was perifused during fractions 7-12 to the luminal side of one device and to the myometrial side of the other device. Regardless of status, prostaglandin secretion rates (PGF and PGE2) were higher (P less than 0.01) from the luminal side than the myometrial side. Secretion rates of PGF were lower (P less than 0.01) for endometria from pregnant cows than for endometria from cyclic or bred/non-pregnant cows, whereas secretion rates of PGE2 were not affected by pregnancy status. Regardless of the side of perifusion, secretion rates of PGF and PGE2 from endometria of cyclic and bred/non-pregnant cows were elevated (P less than 0.01) throughout the period of oxytocin treatment, whereas prostaglandin secretion by endometria from pregnant cows was not stimulated by oxytocin. Decreased secretion of PGF from endometria of pregnant cows suggests that the corpus luteum and pregnancy are maintained because of an inhibition of endometrial prostaglandin synthesis or an inability to respond to stimulators of prostaglandin synthesis (i.e. oxytocin).     

Polyunsaturated fatty acids differentially alter PGF(2alpha) and PGE(2) release from bovine trophoblast and endometrial tissues during short-term culture

Two studies tested the hypothesis that eicosapentaenoic (20:5omega3; EPA), docosahexaenoic acids (22:6omega3; DHA) or linoleic acid (C18:2omega6; LIN) reduced bovine endometrial and trophoblast prostaglandin F(2alpha) (PGF(2alpha)) and prostaglandin E(2) (PGE(2)) release during short-term culture. In Study 1, endometrial tissues were collected from non-lactating, non-pregnant cows and endometrial plus trophoblast tissues from pregnant cows 16 days post-insemination. In Study 2, endometrial and trophoblast tissues were collected on day 17 of pregnancy, from cows synchronised using a double prostaglandin (PG) or Ovagentrade mark synchronisation. Tissues were incubated in medium only (M) or media supplemented with fatty acids: eicosapentaenoic (20:5omega3; EPA), docosahexaenoic acids (22:6omega3; DHA) or linoleic acid (C18:2omega6; LIN). In Study 1, PGE(2) release from 'pregnant' endometria was higher (P=0.094) than from 'non-pregnant' endometria, while PGF(2alpha) concentrations were similar. Fatty acids treatment had no effect on PGF(2alpha) or PGE(2) release from either pregnant or non-pregnant endometria. Individual fatty acid treatments had no effect on the ratio of PGF(2alpha) to PGE(2) from trophoblast tissues, but when the data from the 3 fatty acid treatments were combined (EPA, DHA and LIN treatment groups) the ratio of PGF(2alpha) to PGE(2) was reduced (P=0.026) when compared to medium only. In Study 2, PGE(2) concentrations were higher (P=0.013) from the trophoblast collected from Ovagentrade mark cows as compared to that of the PG synchrony group. When the data from the 3-omega fatty acids were combined (DHA and EPA treatment groups), the 3-omega treatments decreased (P<0.05) PGE(2) biosynthesis from both endometrial and trophoblast tissues from animals synchronised following PG synchrony but not Ovagentrade mark synchrony. Short-term culture with low concentrations of 3-omega fatty acids tended to reduce prostaglandin release from trophoblast collected 16 days after insemination, with the type of synchrony modifying PGE(2) production from the trophoblast tissues collected 17 days after insemination. The ability of exogenous fatty acids to modify embryonic prostaglandin release needs to be examined in the context of supplementing dairy cows with different sources of fats. Synchronisation method altered trophoblast PGE(2) release, highlighting the importance of the hormonal environment in modifying embryonic prostaglandin synthesis and release.     

Separation and culture of ovine endometrial epithelial and stromal cells: evidence of morphological and functional polarity.

Epithelial and stromal cells from endometria of ovariectomized estradiol-treated Corriedale ewes were separated and purified after collagenase digestion. The separation method utilized differences in the speed and ease of detachment of cultured epithelial and stromal cells attached to plastic in response to brief trypsin exposure. Cells were characterized according to morphological, growth, and histochemical criteria. Contamination of each cell type with the other was less than 1%. Separated cells were grown on plastic or on Matrigel-coated Millicell inserts with nitrocellulose membranes. Transmission and scanning electron microscope analyses demonstrated the existence of tight junctions and prominent microvilli in the epithelial cultures on inserts but not on plastic. Asymmetrical secretion of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E (PGE) by epithelial cells provided further evidence of polarization. Epithelial cell secretion of PGF2 alpha was greater than that by stromal cells whereas PGE secretion by stromal cells was greater than that by epithelial cells. Epithelial secretion in the basal direction was approximately 4 and 3 times that of apical secretion for PGF2 alpha and PGE, respectively. The separation protocol provides pure populations of ovine endometrial epithelial and stromal cells and the cultured epithelial cells exhibit characteristics of in vivo morphology and polarized function.     

Prostaglandin F2 alpha output by human endometrium under superfusion and organ culture conditions

Specimens of proliferative and secretory human endometrium were incubated under organ culture or superfusion conditions and the levels of PGF2 alpha in the medium were measured by radioimmunoassay. Basal rates of PGF2 alpha output during short-term superfusions and long-term (1-2 day) batch incubations, performed on the same tissue specimens, were similar. Basal output of PGF2 alpha by proliferative endometrium (230-280 ng/mg protein X d) was significantly higher than that of secretory tissue under both experimental conditions. Estradiol (10(-8) M) increased PGF2 alpha output significantly (4-fold) only in secretory endometrium under organ culture conditions; Progesterone (10(-7) M) decreased it significantly (to 1/2-1/4 of the basal level) in both types of endometria during long-term incubations and in proliferative endometrium during superfusion. Glands isolated from proliferative and secretory endometrium produced PGF2 alpha during superfusion at a rate comparable to that of endometrial tissue under similar conditions. PGF2 alpha output by glands isolated from secretory endometrium increased significantly (3-fold) when estradiol was added to the superfusion medium.     

Effect of pregnancy-specific protein B on prostaglandin F2 alpha and prostaglandin E2 release by day 16-perifused bovine endometrial tissue

Five normal estrous cycling multiparous non-lactating Brahman cows were utilized to determine if pregnancy-specific protein B (PSPB) would alter prostaglandin F2 alpha (PGF) and prostaglandin E2 (PGE) synthesis/release by endometrial tissue. The uterine horn ipsilateral to the corpus luteum was excised on Day 16 of the estrous cycle. Endometrial tissue (200 mg wet wt) was cultured in Nutrient Mixture F-10 medium in a perifusion system. The tissue and medium were aerated with 95% O2: 5% CO2 and temperature was maintained at 39 degrees C. The medium flow rate was 100 microliters/min and fractions were collected at 20 min intervals. After a 120 min settling period, tissue culture continued with: 1) control (medium only); 2) 2 micrograms [Asu1,6]-oxytocin/ml medium for 1 h; 3) 4 or 8 micrograms PSPB/ml medium for 2 h; or 4) 4 or 8 micrograms PSPB/ml medium for 2 h plus 2 micrograms oxytocin/ml medium during the second h. Differences in PGF and PGE secretion rate were not found between 4 and 8 micrograms PSPB. Therefore, groups were combined and data were analyzed according to tissue not receiving PSPB (control); receiving PSPB and receiving PSPB plus oxytocin. A nonsignificant rise (p greater than 0.10) in PGF secretion was observed in response to PSPB and PSPB plus oxytocin above the control by the end of the perifusion period (263.7 +/- 41.7, 220.0 +/- 41.7 and 166.1 +/- 41.7 pg/(100 mg tissue/min), respectively). Treatment with PSPB alone elevated (p less than 0.05) PGE secretion rate above control by 100 and 160 min post-removal of PSPB treatment. Treatment with PSPB plus oxytocin elevated (p less than 0.05) PGE release above control by 20 min after starting oxytocin treatment and continued throughout the duration of the perifusion. Pregnancy-specific protein B plus oxytocin-induced PGE release was greater (p less than 0.05) than PSPB alone after initiating the oxytocin treatment until 20 min after removal of the treatments. However, no further differences between PSPB alone and PSPB plus oxytocin treatments were detected throughout the remainder of the perifusion period. It appears that PSPB tends to elevate PGF release and significantly elevates PGE release from Day 16 endometrial tissue.     

The effect of progesterone and human interferon alpha-2 on the release of PGF2 alpha and PGE from epithelial cells of human proliferative endometrium.

Progesterone and interferon-like trophoblastic proteins modulate prostaglandin (PG) synthesis from endometrium in early ovine and bovine pregnancy. Enriched epithelial cells were prepared from human endometrium removed in the proliferative phase of menstrual cycle (n = 8). Progesterone at a concentration of 1 microM suppressed PGE release from the cells during the first 24 hours in culture. After 48 hours in culture progesterone at a dose of 100 nM and 1 microM suppressed both the release of PGF2 alpha and PGE from the cells and this suppression was maintained for a further two days. Addition of exogenous 30 microM arachidonic acid (AA) abolished this effect of progesterone on both PGF2 alpha and PGE release. Interferon alpha-2 did not suppress the basal release of PGF2 alpha nor PGE. In the presence of progesterone, interferon alpha-2 attenuated the progesterone mediated suppression of PGF2 alpha but not PGE release from endometrial cells. These findings suggest that progesterone suppresses the basal release of PGs from human endometrium, but unlike the sheep, interferon alpha-2 does not exert this action on human endometrium.     

Prostaglandin secretion by perifused bovine endometrium: Secretion towards the myometrial and luminal sides at day 17 post-estrus as altered by pregnancy

Bilateral perifusion devices were utilized to measure prostaglandin secretion towards luminal and myometrial sides of bovine endometria. Tissues were collected at Day 17 post-estrus from cyclic (n=4), pregnant (n=5) and bred but subsequently non-pregnant (n=6) cows. Tissue from each cow was placed into two perifusion devices, perifused with Krebs-Ringer Bicarbonate solution (3 ml/10 min) for 2.5h and fractions collected every 10 min. Oxytocin (1 IU/ml) was perifused during fractions 7–12 to the luminal side of one device and to the myometrial side of the other device. Regardless of stratus, prostaglandin secretion rates (PGF and PGE₂) were higher (P< 0.01) from the luminal side than the myometrial side. Secretion rates of PGF were lower (P< 0.01) for endometria from pregnant cows than for endometria from cyclic or bred/non-pregnant cows, whereas secretion rates of PGE₂ were not affected by pregnancy status. Regardless of the side of perifusion, secretion rates of PGF and PGE₂ from endometria of cyclic and bred/non-pregnant cows were elevated (P< 0.01) throughout the period of oxytocin treatment, whereas prostaglandin secretion by endometria from pregnant cows wasnot stimulated by oxytocin. Decreased secretion of PGF from endometria of pregnant cows suggests that the corpus luteum and pregnancy are maintained because of an inhibition of endometrial prostaglandin synthesis or an inability to responsd to stimulators of prostaglandin synthesis (i.e. oxytocin).     

Increased and intermittent prostaglandin release from amnion detected by a new superfusion technique for full thickness fetal membrane

Prostaglandin E2 (PGE) and F2 alpha (PGF) release by the intact fetal membranes is described using a novel superfusion technique allowing for the independent assessment of prostaglandin release from the amnion and chorio-decidua whilst maintaining the anatomical integrity of the fetal membranes. The effect of labour on prostaglandin release is described. Using this system it was confirmed that the amnion is a major site of prostaglandin release and possibly production. Labour resulted in a significant increase of both PGE and PGF release from the amnion side only (Pre-labour: PGE 918 pg/cm2/3h, PGF 370 pg/cm2/3h; Labour: PGE 2993 pg/cm2/3h, PGF 662 pg/cm2/3h). No change in either PGE or PGF release from the chorio-decidual side was observed in relation to labour. In addition a change in the pattern of prostaglandin release from the amnion was observed in tissues obtained after the onset of labour. In 6 of 8 samples obtained after spontaneous labour an intermittent or pulsatile release of both PGE and PGF was observed from the amnion side as compared to the steady state of prostaglandin release from all 10 samples obtained before labour.     

Oxytocin-induced prostaglandin release from perifused bovine caruncular and intercaruncular endometrial tissue on days 20, 30 and at first estrus postpartum

Twenty-two multiparous Brahman x Hereford F1 cows were utilized to determine the effect of oxytocin (OT) on prostaglandin F2 alpha (PGF) release from caruncular and intercaruncular endometrial tissues and prostaglandin E2 (PGE) release from intercaruncular tissue. The previously gravid uterine horn was removed on d 20 postpartum (n = 7), on d 30 postpartum (n = 7) or the uterine horn ipsilateral to the dominant follicle was removed 12-18 h after onset of first behavioral estrus postpartum (ES; n = 8). Tissues (200 mg wet wt) were cultured in Nutrient Mixture F-10 medium in a perifusion system. The medium and tissues were aerated with 95% O2: 5% CO2 and temperatures were maintained at 39 degrees C. The flow rate was 100 microliters/min and fractions were collected at 20 min intervals for 400 min. After a 2 h settling phase, the tissues were challenged with 1, 2 or 4 micrograms [Asu1,6]-OT/ml of media for 1 h. Basal release of PGE and PGF on d 20 was greater than on d 30 and at ES (P less than .02) which were similar. All doses of OT increased PGE and PGF with both remaining elevated throughout the duration of the perifusion (P less than .008). However, there were no differences among doses. Release of PGE in response to OT on d 20 and 30, was higher than at ES (P less than .008). More PGF was released in response to OT from intercaruncular than caruncular tissue on d 20 (P less than .0001) and at ES (P less than .003). Release of PGF in response to OT on d 20 was higher (P less than .0001) than on d 30 and d 30 was higher than at ES (P less than .007). Basal and OT-induced release of PGE and PGF declined as day postpartum increased. We conclude that intercaruncular tissue released more PGF than caruncular tissue and both intercaruncular and caruncular tissue responded to OT with a sustained release of prostaglandins in a non-dose-dependent manner on d 20, 30 and at ES postpartum.     

Specific production of prostaglandin E by human amnion in vitro

Prostaglandin production by intra-uterine human tissues has been investigated using a method of tissue superfusion. Tissues were obtained at elective Caesarean section and after spontaneous vaginal delivery. It was found that all the tissues studied (amnion, chorion, decidua and placenta) produced more prostaglandin E (PGE) and 13,14-dihydro-15-keto-prostaglandin F (PGFM — the major circulating metabolite of prostaglandin F) than prostaglandin F (PGF). Amnion produced significantly more PGE (but not PGF or PGFM) than any other tissue. Prostaglandin production by each tissue was similar whether it was taken at elective Caesarean section or after spontaneous vaginal delivery.     

Trauma-induced human endometrial prostaglandin concentrations

Controversy still continues concerning the factors controlling endometrial prostaglandin concentrations measured under different circumstances. In this study an attempt was made to remove serial samples of normal human endometrium and standardise 4 different short incubation periods at room temperature before snap-freezing the tissue. No significant difference was found in the concentrations of PGE2 and PGF2 alpha, or PGE2/PGF2 alpha ratio, of the series of specimens with the shortest incubation (42.7 seconds) compared with the longest (93.1 secs). The most likely explanation for this is that trauma-induced prostaglandin production is such a rapid process that it is generally complete within less than 30 seconds at room temperature. As reported in previous studies, a significant correlation was found between PGE2 and PGF2 alpha concentrations in some specimens. Large and significant variations in concentration of prostaglandins were found between individuals which were partly accounted for by variations in stage of the menstrual cycle at the time of collection.     

Endothelin-1 stimulates prostaglandin F2 alpha release from human endometrium

Despite a key role in the pathogenesis of menorrhagia, the factors controlling the uterine vascular bed are poorly understood. This study has assessed the effects of the potent vasoconstrictor endothelin (ET)-1 on prostaglandin (PG) release from human endometrial explants in short-term culture. There was no significant difference between the production of PGF2 alpha in proliferative and secretory tissue (1709 and 2434 pg/mg/h--median values, range 70,3745 and 219,6700 pg/mg/h). Less PGE was released than PGF2 alpha, and the amount did not vary with the phase of the menstrual cycle (308 and 296 pg/mg/h (range 65,387 and 105,429) for proliferative and secretory tissue). ET-1 (10 and 100 nM) and arachidonic acid (AA, 30 microM), stimulated PGF2 alpha release from proliferative, but not secretory endometrium, by 78%, 86% (P less than 0.01) and 80% respectively, compared with control tissue. No effect was seen on PGE release. ET-1 may play a role in the local control of the endometrial vascular bed either directly, or via the release of PGF2 alpha.     

Effect of phorbol ester on prostaglandin regulation of proliferation in rabbit endometrial cells

We have proposed that two of the endogenously synthesized endometrial prostaglandins, prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E1 (PGE1), play a regulatory role in growth control of the endometrium. PGF2 alpha increases DNA synthesis and PGE1 inhibits that effect. Primary cultures of rabbit endometrial cells were used here to examine the effects of the tumor-promoting, diacylglycerol mimicking, phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA), on the prostaglandin control of cell proliferation. TPA treatment of these cultures results in: a decrease in control levels of proliferation and complete inhibition by TPA of PGF2 alpha stimulated DNA synthesis; a reduction in [3H]PGF2 alpha binding with short term treatment but an increase to above control binding level with long term treatment; an inhibition of the normal PGF2 alpha stimulated inositol polyphosphate synthesis; and a small increase in accumulation of PGF2 alpha in the culture media. Furthermore, in this culture system, TPA does not down regulate [3H]PGE1 binding; it does not alter the normal PGE1 stimulation of cAMP synthesis; and it has no effect on the normal endogenous PGE1 synthesis by these cultures. The above results are consistent with our previous observations that PGF2 alpha works through the intracellular messengers inositol polyphosphate/diacylglycerol whereas PGE1 works through cAMP.     

Eicosanoids production in endometriosis

In order to investigate the production of eicosanoids in human endometrium, myometrium, leiomyoma, adenomyosis, normal ovary, non-endometrial cyst and endometrial cyst, slices of each tissue were incubated. 6-Keto-prostaglandin (PG) F1 alpha, thromboxane (TX) B2, PGF2 alpha and PGE2 concentrations in the incubation medium were measured by direct RIA. 6-Keto-PGF1 alpha production of adenomyosis was significantly higher than that of endometrium, myometrium and leiomyoma, especially in the menstrual phase. The production of eicosanoids in endometrial cyst was significantly higher than that of non-endometrial cyst and normal ovary. These results suggest that endometriosis is associated with increased eicosanoid production in vivo.     

The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia

The effects of four medical treatments have been assessed on menstrual blood loss (MBL) and endometrial prostaglandin (PG) concentrations in 30 women with objectively confirmed menorrhagia. Patients were randomly treated with danazol, 200 mg daily (n = 6), mefenamic acid, 500 mg three times daily during menses (n = 8), norethisterone, 5 mg twice daily from day 15-25 of the cycle (n = 8) or a progesterone-impregnated coil releasing 65 micrograms progesterone daily (n = 8). Endometrial biopsies were obtained in the mid-luteal phase before and after treatment in 23 cases, and assayed for PG content using radioimmunoassay. Treatment with norethisterone had no effect on either MBL or the concentration of PGs in the endometrium. MBL was significantly reduced after treatment with mefenamic acid (P = 0.05, n = 6) and the progesterone coil (P less than 0.05, n = 6), and was reduced in each of 4 cases treated with danazol in whom endometrial biopsies were available. Although there was no consistent change in endometrial PG concentrations in either the mefenamic acid or danazol groups, the lower MBL after insertion of the progesterone coil was associated with a reduced endometrial content of PGE, PGF2 alpha and "total" PG (6oxo PGF1 alpha + PGE + PGF2 alpha)-P = 0.05. Whereas the cyclooxygenase inhibitor mefenamic acid is likely to exert its effect on endometrial PGs at the time of menstruation itself, the continuous administration of progesterone throughout the menstrual cycle could result in both an impairment in estrogen receptor generation leading to reduced estrogen-mediated cyclooxygenase activity, and an increase in endometrial PG metabolism.     

The effects of Arcanobacterium pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo

Uterine bacterial infection after parturition causes endometritis, perturbs ovarian function and leads to infertility in cattle. Although endometritis is caused by mixed infections, endometrial pathology is associated with the presence of Arcanobacterium pyogenes. The aims of the present study were to determine the effects of A. pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo. Heat-killed A. pyogenes did not affect the production of prostaglandin F2alpha (PGF) or prostaglandin E(2) (PGE) from endometrial explants, or purified populations of endometrial epithelial or stromal cells. However, the explants produced more PGF and PGE than controls when treated with a bacteria-free filtrate (BFF) cultured from A. pyogenes. Similarly, BFF stimulated PGF and PGE production by epithelial and stromal cells, respectively. So, BFF or control PBS was infused into the uterus of heifers (n=7 per group) for 8 days, starting the day after estrus. Emergence of the follicle wave, dominant follicle or corpus luteum diameter, and peripheral plasma FSH, LH, estradiol, progesterone, PGFM, or acute phase protein concentrations were unaffected by the BFF infusion. In the live animal it is likely that the intact uterine mucosa limits the exposure of the endometrial cells to the exotoxin of A. pyogenes, whereas the cells are readily exposed to the toxin in vitro.     

Ovarian and uterine prostaglandin E2-9-ketoreductase activity in cyclic and pregnant ewes.

The regulation of luteal function in sheep appears to be dependent in part upon relative utero-ovarian concentrations of PGE2 and PGF2 alpha. Prostaglandin E2-9-ketoreductase converts PGE2 (a putative antiluteolysin) to PGF2 alpha. Enzymatic activity was measured in a cytosolic subcellular fraction of luteal and endometrial tissues collected on days 10, 13 and 16 of the estrous cycle or pregnancy. Respective days represented times before, during, and after the critical period for maternal recognition of pregnancy. Preparations of enzyme were incubated in the presence of tritiated PGE2. Radiolabeled PGF2 alpha (ie., product) was separated from PGE2 by gel filtration chromatography and quantified by liquid scintillation spectrometry. There were no significant differences due to time of tissue collection or pregnancy status in enzymatic activity of luteal tissues. Prostaglandin E2-9-ketoreductase activity isolated from endometria of open ewes was greater than their pregnant counterparts on days 13 and 16. Thus, the potential capacity of the ovine uterus to generate luteolytic PGF2 alpha from PGE2 substrate is elevated during an infertile estrous cycle.     

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 in vitro on prostaglandin (PG) output from guinea-pig endometrium, removed on days 7 and 15 of the oestrous cycle and maintained in tissue culture for 3 days, have been investigated. Oestradiol (3.7 to 3700 nM) and oxytocin (2 to 200 pM) did not stimulate endometrial PGF2 alpha output, thus not confirming the findings of a previous report (Leaver & Seawright, 1982), nor did they stimulate the outputs of PGE2 and 6-keto-PGF1 alpha. In fact, oestradiol (3700 nM) inhibited the outputs of PGF2 alpha, PGE2 and, to a lesser extent, 6-keto-PGF1 alpha. Progesterone (3.2 to 3200 nM) inhibited the outputs of PGF2 alpha and PGE2; hydrocortisone (2.8 to 2800 nM) 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-PGF1 alpha output, suggesting that the mechanisms controlling endometrial PGI2 synthesis (as reflected by measuring 6-keto-PGF1 alpha) are different from those controlling endometrial PGF2 alpha and PGE2 synthesis.     

Correlation between dysmenorrheic severity and prostaglandin production in women with endometriosis.

The role of prostaglandins (PGs) in dysmenorrhea of endometriosis is poorly understood. The relationship between dysmenorrheic severity and prostaglandin production was investigated in endometriosis. Slices of normal myometrium, adenomyosis, normal ovary and endometrial cyst were incubated. 6-Keto-PGF1 alpha (a metabolite of PGI2), TXB2 (a metabolite of TXA2), PGF2 alpha, and PGE2 concentrations of the incubation medium were measured by RIA. The results showed that 6-keto-PGF1 alpha production in adenomyosis and endometrial cyst were significantly higher than those in normal myometrium and ovary. A direct relationship between the degree of dysmenorrheic severity and PGs production in tissue in endometriosis was observed.