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.     

Prostaglandins in fetal tracheal and amniotic fluid from late pregnant sheep

Concentrations of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in fetal tracheal and amniotic fluid from chronically catheterized sheep during late pregnancy. Amniotic fluid contained significantly greater concentrations of these prostaglandins than tracheal fluid (p less than 0.01); there was no correlation between the level of prostaglandins found in each fluid. In tracheal fluid concentrations of PGE and PGFM exceeded those of PGF (P less than 0.01) whereas no significant differences were found in amniotic fluid. The levels of prostaglandins in these fluids were similar in ewes bearing hypophysectomized fetuses.     

Specific changes in the production of prostanoids by the ovine cervix at parturition

A method of tissue superfusion has been used to measure prostanoid production by the ovine cervix during late pregnancy and at parturition. In late pregnancy (105–135 days of gestation) cervical tissue produced relatively large amounts of prostaglandin E (PGE); in comparison, the production rates of prostaglandin F (PGF), 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) and 6-oxo-prostaglandin F_1α were generally low. Thromboxane B₂ (TXB₂) production was minimal and often unmeasurable. There were significant increases in the production rates of PGE and 6-oxo-PGF_1α by cervical tissue taken immediately after delivery, when compared to late pregnancy. Mean production rates of PGE increased from 19.8 ± 4.1 to 43.8 ± 7.4 ng/g. dry wt./min; 6-oxo-PGF_1α production rates increased more than three-fold from 10.0 ± 2.7 to 34.6 ± 9.8 ng/g. dry wt./min (means ± S.E.M.). There were no significant differences in the rates of production of PGF, PGFM and TXB₂ by the two groups.     

Fetal-maternal secretion of prostaglandins in the cow

A study was conducted to measure the blood plasma concentrations of prostaglandin F2 alpha (PGF2 alpha), 13,14-dihydro-15-keto-prostaglandin F (PGFM), 6-keto-prostaglandin F1 alpha (6-keto), prostaglandin uterine artery, uterine vein, umbilical artery and umbilical vein in 24 cows from days 80 to 260 of pregnancy. Blood was collected during surgery and all prostaglandins were measured using specific radioimmunoassay procedures. Results indicate that PGF2 alpha blood levels are higher in the umbilical vessels and uterine vein than in the ovarian vein and uterine artery. PGFM and PGE2 showed a trend towards higher values in the umbilical than in the maternal vessels, but the levels of 6-keto and TBX2 were not different among the vessels studied. No differences across time could be observed in any of the prostaglandins measured, partly due to the great variability in blood levels among animals during the same stage of pregnancy.     

Uterine activity and prostaglandin production following intraamniotic hyperosmolar urea

The relationship between endogenous prostaglandin (PG) production and uterine activity was studied in hyperosmolar urea induced abortion patients. Polygraphic recordings of intraamniotic pressure were obtained at periodic intervals following intraamniotic injection of 80 gm urea. At 0, 0.25, 1, 4 and 8 hours amniotic fluid and blood samples were obtained for PGE, PGF and 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM) analysis by radioimmunoassay. Blood was also sampled at time of absorption. In eight patients studies, uterine tone was elevated by 0.25 hour although no rhythmic contractions were observed by 1 hour. At 4 hours, amniotic fluid PGF concentration increased significantly (P < .01) over the pre-injection value and continued to increase at 8 hours. Amniotic fluid PGE, PGFM and all plasma PG's showed no change during the 8 hour period following urea administration. At time of abortion the plasma PGFM concentration was significantly greater than at the time of injection (238 ± 54.4 vs. 86.7 ± 7.3 pg/ml). There was no significant differences between pre-injection and absorption plasma PGF or PGE concentrations. In the present study, there is no evidence that increased prostaglandin production precedes urea induced contractions. The possible role of PG's in uterine contractions is discussed.     

Maternal and feto-placental prostanoid responses to a single course of antenatal betamethasone

We tested the hypothesis that antenatal betamethasone alters prostanoid levels in the maternal and feto-placental compartments. Forty-three singleton pregnancies were studied. Group I were women treated with a single course of antenatal betamethasone and who delivered <37 weeks gestation; Group II were untreated women who delivered <37 weeks; and Group III were untreated women who delivered >38 weeks. Maternal and mixed cord blood; and placental samples were collected at delivery and analyzed for PGE2, PGF(2alpha), 6-ketoPGF(1alpha), and TxB2 levels. Antenatal betamethasone decreased maternal PGE2 levels with concomitant increases in the feto-placental compartment. Umbilical cord TxB2 levels in the treated group were significantly lower than the non-treated pre-term and term groups resulting in a higher 6-ketoPGF(1alpha):TxB2 ratio. Considering the regulatory role of PGE2 and PGI2 in fetal lung development and neonatal transition homeostasis, these results suggest a mechanism, at least in part, for the beneficial effects of antenatal steroids on fetal lung maturation and neonatal cardio-pulmonary homeostasis at birth.     

Effects of prostaglandins on the cerebral circulation in the goat

The role of prostaglandins in producing cerebrovasodilation during hypercapnia was tested in goats. Cerebral blood flow (CBF) changes with increasing arterial PCO2 were measured before and after prostaglandin synthesis inhibition with indomethacin or ibuprofen. Both drugs produced significant decreases in CBF under control anesthetized conditions but had no significant effect on the cerebrovascular response to increased arterial PCO2. The effects of direct intracerebrovascular infusion of prostaglandin E₂ (PGE2), prostaglandin F2α (PGF2α) and prostacyclin were also measured. In the dose range tested (0.1–1 ug/min) PGF2α had no significant effect on cerebral blood flow (CBF). Both PGE2 and PGI2 produced an increase in CBF and the increase produced by PGI2 was significantly greater than that produced by PGE2. The effectiveness of each compound in producing cerebrovascular changes is consistent with the endogenous distribution of prostaglandins within the brain. These results suggest that prostaglandins, particularly PGI1, may be important in modulating cerebrovascular tone but have no role in increasing CBF during hypercapnia.     

Uterine prostaglandin concentrations following fetal death in sheep

Concentrations of prostaglandin E (PGE), PGF and 6-oxo-PGF_1α (the hydrolytic product of PGI₂) were measured by radioimmunoassay (RIA) in myometrium, endometrium, cotyledons, amnion and chorioallantois taken from different uterine areas from chronically catheterized sheep bearing fetuses which had died 12–26 h previously (n=4) or 34–72 h previously (n=4). These two groups of animals were designated fetuses dead <30 h and >30 h respectively. The time of fetal death was assessed on the basis of fetal heart rate and blood gases. At the time of the tissue collection the ewes were between 123 and 130 days after mating. For comparative purposes, tissues also were collected from four sheep bearing live chronically catheterized fetuses at 130 days of gestation.For myometrium, concentration of PGF, PGE and 6-oxo-PGF_1α were significantly higher in sheep bearing dead fetuses, compared to those bearing live fetuses. Analysis of variance also showed a significant effect of uterine area on myometrial PGE concentrations, concentrations being higher in tubal areas than elsewhere. Concentrations of PGE, PGF and 6-oxo-PGF_1α were higher in endometrium taken from uteri containing dead fetuses. In cotyledons, concentrations of PGF and 6-oxo-PGF_1α but not PGE, were significant elevated following fetal death. Concentrations of 6-oxo-PGF_1α, but not PGE or PGF, were elevated in both chorioallantois and amnion of sheep bearing dead fetuses, compared to those bearing live fetuses. In association with elevated PG concentrations, there was a progressive increase in the frequency and maximum amplitude of uterine contractions. These results show that PG concetrations are elevated following fetal death in sheep, and suggest an association between elevated PG concentrations and delivery of the dead fetus.     

Improvement of radioimmunoassays for prostaglandins in bovine blood plasma and their application to monitor reproductive functions

Efficient RIA procedures are required for determination of prostaglandins (PGF(2alpha), PGE(2), PGI(2) and their metabolites) in bovine blood plasma to elucidate their significance in reproductive endocrinology. A new rapid efficient prepurification was developed using commercial octadecyl silicagel cartridges. Prepurification is especially necessary for the determination of 13,14-dihydro-15-keto-PGE(2) (PGEM). After prepurification, PGEM was first converted into the more stable 13,14-dihydro-15-keto-PGA(2) (PGAM) and measured in a RIA-system for PGAM. For PGF(2alpha), 13,14-dihydro-15-keto-PGF(2alpha) (PGFM), PGE(2) and 6-keto-PGF(1alpha) direct tests using 50 mul plasma per tube were elaborated. The validity of the tests was monitored by high performance liquid chromatography radioimmunoassay (HPLC RIA ). Infusion studies using PGF(2alpha) and PGE(2) showed that about 10% of these hormones remained unmetabolized after the first passage through the lungs. The biological half life of the metabolites PGFM and PGEM in bovines was estimated to be 4 min. Thus, PGFM and PGEM measurements in the peripheral circulation reflect even short-term secretory changes of PGF(2alpha) and PGE(2). During the infusion of PGF(2alpha) the levels of progesterone decreased but were not affected by PGE(2). Both prostaglandins caused increased oxytocin secretion. In the cow peripartum first PGEM elevations were measured 5 to 8 d ante partum, whereas PGFM increased 1 to 2 d ante partum. Then both prostaglandins increased simultaneously until parturition. In the postpartal phase PGFM was higher than PGEM, and both prostaglandins remained elevated for several days. Prostacyclin levels remained unchanged during the peripartal period.     

Prostaglandin F2 alpha as the luteolysin in swine: VI. Hormonal regulation of the movement of exogenous PGF2 alpha from the uterine lumen into the vasculature

To test the endocrine-exocrine theory of maternal recognition of pregnancy in the pig 16 gilts were assigned randomly to a 2 X 2 factorial involving pretreatment with sesame oil (SO) or estradiol valerate (5 mg; EV) injected on Days 11 through 14 of the estrous cycle and an intrauterine injection of saline (5 ml; SA) or prostaglandin F2 alpha (50 micrograms; PGF) on Day 14. Peripheral blood samples were collected for 120 min postinjection and analyzed for 15-keto-13,14-dihydro-PGF2 alpha (PGFM). PGFM concentrations were lower in EV than SO gilts (438 vs. 844 pg/ml; p less than 0.05). There was heterogeneity of regression between EV and SO gilts (p less than 0.01), with EV gilts having a slower release of PGF from the uterine lumen into the vasculature. Prostaglandin F2 alpha did not increase mean PGFM concentrations (p greater than 0.10), but resulted in an altered temporal pattern of PGFM (p less than 0.05) compared to SA gilts. There was an interaction between the two treatments over time, with EV-PGF gilts demonstrating a slower, more gradual release of PGFM than SO-PGF gilts. To test whether prostaglandins of the E series were involved in this mechanism, gilts were assigned to two 4 X 4 latin squares balanced for residual effects and treated with saline or flunixen meglumine (Banamine). Each gilt was treated with four PGE:PGF infusion sequences (SEQ) in each uterine horn: phosphate-buffered saline (PBS; PBS-SEQ), PGE1 (50 micrograms), PGE2 (50 micrograms), and PGE1 (25 micrograms) + PGE2 (25 micrograms) (PGE-SEQ), with each infusion followed 15 min later by PGF (25 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandin concentrations in intra-uterine tissues from late-pregnant sheep before and after labour

Prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in cotyledons and myometrium from sheep before and after labour. Fetal cotyledons contained more PGE than maternal cotyledons which in turn contained more than myometriu. The maternal cotyledon contained the highest concentrations of PGF, but the fetal cotyledon was the only tissue exhibiting a statistically significant rise in the concentration of PGF following labour. Concentrations of PGFM were closely correlated with (although usually lower than) those of PGF.     

Prostaglandin concentrations in peripheral plasma and ovarian and uterine plasma and tissue in relation to oviposition in hens

An increase in the plasma concentrations of prostaglandins (PGs) is associated with uterine contractile activity and with oviposition in the hen. In order to assess the contribution of potential sources of prostaglandins to the increase in prostaglandin levels observed at oviposition, prostaglandins E2, F2 alpha, and 13,14-dihydro-15-keto PGF2 alpha (PGFM, the stable but biologically less active metabolite of PGF2 alpha) were measured in plasma from the brachial vein, ovarian follicular vein and uterine vein, and in tissues from ovarian follicles and the uterus 12 h before and at midsequence oviposition or a terminal oviposition. These two ovipositions differ in that a midsequence oviposition is followed within 0.25-1.0 h by the next ovulation of the sequence, whereas the terminal oviposition is followed by an ovulation 14 h later. The concentration of PGFM in plasma from the brachial vein increased at midsequence oviposition, while the levels of PGE2 were unchanged. Prostaglandin E2, F2 alpha, and FM levels were each similar in the plasma from the brachial and uterine veins at the time of midsequence oviposition. In plasma from the largest preovulatory follicle, the concentration of PGF2 alpha and PGFM increased 19- and 7-fold, respectively, from 12 h before midsequence oviposition to midsequence oviposition, although no changes were observed in the concentrations of PGE2 during this interval. The levels of PGF2 alpha increased in the tissues of the two largest preovulatory follicles and the two most recently ruptured follicles during the 12-h period before a midsequence oviposition, while there was no change or a decrease in PGE2 levels in these tissues during the same interval. In contrast, the concentration of PGF2 alpha did not increase during the 12-h period preceding the terminal oviposition of the sequence in plasma from the brachial, uterine, or follicular veins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pre-ovulatory changes in cyclic AMP and prostaglandin concentrations in follicular fluid of gilts

The concentrations of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) and prostaglandins E and F (PGE and PGF) were determined in follicular fluid collected from follicles of prepubertal gilts at various times after treatment with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to induce ovulation. The concentrations of cyclic AMP, PGE and PGF in the follicular fluid after PMSG treatment but prior to hCG injection were about 1 pmol/ml, 1 ng/ml and 0.2 ng/ml, respectively. After hCG administration, the follicular fluid levels of cyclic AMP increased markedly, reaching a peak (400-fold increase) about 4 h after injection and then declined gradually to pre-hCG levels. A second rise (2.5- to 5-fold increase) occurred about 30 h after hCG with the levels being sustained up to the expected time of ovulation. In contrast, the levels of PGE and PGF remained relatively constant until 28–30 h after hCG treatment. Thereafter, the concentrations of both prostaglandins began to rise with the increases becoming more pronounced and reaching maximal values as the expected time of ovulation approached. These data provide further evidence for a physiological role of follicular prostaglandins in the process of ovulation but do not support an obligatory role for prostaglandins in the acute gonadotropin stimulation of cyclic AMP formation.     

Alterations in uterine and placental prostaglandin F and E with gestational age in the rat

Experiments were designed to determine the chronological alterations in placental and uterine prostaglandin F and E (PGF and PGE) during pregnancy in the rat. Pregnant rats (sperm in the vagina = day 0) were sacrified at days 15, 18,19, 20, 21 and delivery (day 21 ) and placental and uterine tissues assayed (RIA) for PGF and PGE immediately (“ ”) or after 1 hour incubation (“ ”). Uterine content of PGF and PGE (ng PG/mg DNA) was increased significantly by day 19 and further increases were seen through delivery. Incubation of uterine tissue resulted in enhanced net production of PGF and PGE (p <.05) per mg DNA (as judged by tissue content and release into the incubation medium) by day 18 of pregnancy vs. day 15. Net production peaked around the time of delivery thus paralleling the alterations in tissue content .By contrast, no differences with gestational age were found in placental content of PGF and PGE , the concentrations throughout late gestation remaining in the range of uterine PGs at day 15. However, production of PGs per mg placental DNA increased markedly during incubation with significant enhancement detected by day 19 vs. 15, achieving levels even greater than the uterus .The and findings for the uterus are consistent with the hypothesis that increases in uterine PGs levels at the end of pregnancy may play an important role in parturition. The experiences with placental tissue suggest that the potential for PG production per placental cell may also increase in late gestation and thereby contribute to the augmented intrauterine availability of PGs at that time.     

Inhibitory effects of dispersed human amnion cells on production rates of prostaglandin E and F by endometrial cells

Dispersed cells were prepared from amniotic membranes obtained either by caesarian section near term before labos (CS) or after spontaneous vaginal delivery (SL) and from human endometrial curettings. The cells were maintained separately in primary culture for about 18 h. Production rates (PR) of PGE and PGF during incubation for 1 h in defined medium were determined whent the cell-types were separate (n=60) or combined (n=27) and when endometrial cells were incubated in medium conditioned by CS amnion cells (n=13) or SL amnion cells (n=12). The PR of PGE by CS amnion cells was five times greater than that of PGF and there was a two-fold increase (p <0.01) in PGE but not PGF by SL cells. Co-incubation was associated with a 25–32% fall in PR of both PGE and PGF (p <0.01) compared to the sum from separately incubated cells when CS cells were used whereas values for co-incubated SL cells did not differ from controls. Conditioned medium from CS but not SL cells inhibited PGE and PGF output by 30% and 40% (p <0.01) respectively. These findings suggest that human amnion cells release an inhibitor of prostaglandin synthesis in endometrial cells.     

Prostaglandin production in the umbilical and uterine circulations in pregnant sheep at 129-136 days gestation.

Prostaglandins circulating in the maternal and foetal blood have been implicated in important physiological systems. These functions include foetal adrenal function, maintenance of patency of the ductus arteriosus, regulation of uterine and umbilical circulations, and labor and delivery type myometrial contractions. The placenta is a major site of prostaglandin production in pregnancy. Limited data are available which combine measurements of veno-arterial differences across the uterine and umbilical circulations with blood flow in these circulations to enable calculation of umbilical-placental and utero-placental production rates for the prostaglandins. In chronically instrumented pregnant ewes, between 129 and 136 days of gestation, prostaglandin F2 alpha(PGF2 alpha), 13, 14 dihydro-15-keto prostaglandin F2 alpha (PGFM), prostaglandin E2 (PGE2) were measured in the maternal carotid artery and uterine vein. Foetal PGE2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (the major metabolite of prostacyclin) were measured in umbilical venous and foetal descending aorta arterial plasma. Umbilical and uterine blood flow were measured using the diffusion-equilibrium technique. Uterine blood flow was 1693 +/- 137 ml.min-1 (mean +/- SEM); uterine production rates were 480 +/- 88 ng.min-1 for PGF2 alpha, 517 +/- 144 ng.min-1 for PGFM, and 165 +/- 27 ng.min-1 for PGE2. Umbilical blood flow was 147 +/- 17 ml.min-1.kg-1 foetal body weight. Umbilical production rates into the foetal circulation were 11 +/- 2 ng.min-1.kg-1 for PGE2 and 6 +/- 2 ng. ng.min-1.kg-1 foetal body weight for PGI2.     

Changes in the plasma prostaglandin F2 alpha metabolite before and during spontaneous labor and labor induced by amniotomy, oxytocin and prostaglandin E2

To elucidate the role of endogenous prostaglandin F2 alpha in spontaneous and induced labor, plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were determined before the onset of labor, at onset of labor, during active labor, at the crowning of the fetal head, and 1 and 2 hours after delivery. Patients in spontaneous labor and labor induced by amniotomy, oxytocin, and prostaglandin E2 were studied. The levels of plasma PGFM in patients who entered spontaneous labor fell 2 to 3 weeks before delivery, whereas those in the induced labor group did not change until the time of induction. Although the levels of PGFM rose gradually with the progress of labor in all cases, the levels in the spontaneous labor were significantly lower in each stage than in the corresponding stage of induced labor. These results suggest that endogenous prostaglandin F2 alpha (PGF2 alpha) production decreases 2-3 weeks prior to the spontaneous onset of labor and is increased again as labor progresses, that the patterns of PGF2 alpha production are similar to each other during spontaneous labor and labor induced by various methods. Therefore, it is felt that endogenous PGF2 alpha may participate in the progress of all kinds of labor.     

Effect of exogenous melatonin on in vivo and in vitro prostaglandin secretion in Rasa Aragonesa ewes

The effect of exogenous melatonin on prostaglandin secretion was measured on Rasa Aragonesa ewes. Fourteen ewes received an 18 mg melatonin implant (M+) on 10 April and were compared with 13 control animals (without implants M-). Twenty days later, intravaginal pessaries were inserted in all animals to induce a synchronized oestrus (day 0). On day 14, ewes were injected, i.v., with 0.5 IU oxytocin. Plasma 15-ketodihydro-PGF(2alpha) (PGFM) concentrations were measured to assess uterine secretory responsiveness to oxytocin. After euthanasia, pieces of endometrium were collected to determine progesterone content and PGE(2) and PGF(2alpha) secretion in vitro, in the presence or absence of either 20 microg/ml recombinant ovine interferon-tau (roIFNt) or 1 nmol/l oxytocin in the medium. Endometrial progesterone content was similar in the two treatments (M+: 50.25+/-17.34 ng/mg tissue, M-: 43.08+/-11.21 ng/mg tissue). M+ ewes that responded to oxytocin had significantly higher plasma PGFM concentrations between 10 and 80 min after oxytocin administration, a higher mean PGFM peak (P<0.001), higher plasma PGFM levels after the challenge (P<0.05) and higher plasma progesterone concentrations (P<0.01) than control ewes. In the in vitro experiment, M+ and M- control samples secreted similar amounts of PGE(2). The presence of roIFNtau and oxytocin only stimulated PGE(2) production (P<0.05) in M- tissues. Control M+ tissues secreted higher amounts of PGF(2alpha) (P=0.07) and PGF(2alpha) secretion was significantly (P<0.01) stimulated by roIFNtau. Oxytocin produced this effect only in M- samples (P<0.01). In conclusion, although previous studies have demonstrated a positive effect of melatonin on lamb production, PGF(2alpha) secretion is higher in vitro and the PGE(2):PGF(2alpha) ratio is unfavourable in response to IFNtau, which could affect embryo survival. Whether or not these mechanisms are similar in pregnant ewes remains to be elucidated.     

Specific changes in the in vitro production of prostanoids by the ovine cervix at parturition

A method of tissue superfusion has been used to measure $\text{in vitro}$ prostanoid production by the ovine cervix during late pregnancy and at parturition. In late pregnancy (105–135 days of gestation) cervical tissue produced relatively large amounts of prostaglandin E (PGE); in comparison, the production rates of prostaglandin F (PGF), 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) and 6-oxo-prostaglandin F_1α were generally low. Thromboxane B₂ (TXB₂) production was minimal and often unmeasurable. There were significant increases in the production rates of PGE and 6-oxo-PGF_1α by cervical tissue taken immediately after delivery, when compared to late pregnancy. Mean production rates of PGE increased from 19.8 ± 4.1 to 43.8 ± 7.4 ng/g. dry wt./min; 6-oxo-PGF_1α production rates increased more than three-fold from 10.0 ± 2.7 to 34.6 ± 9.8 ng/g. dry wt./min (means ± S.E.M.). There were no significant differences in the rates of production of PGF, PGFM and TXB₂ by the two groups.     

Periovulatory changes in ovarian prostaglandin formation and their hormonal control in the rat

The concentration of prostaglandins of the E-group (PGE) and F-group (PGF) and the activity of prostaglandin-synthetase in rat ovaries increased on the evening of the day of proestrus and reached a peak at 5.00 h on the following morning, i.e. about the time of ovulation. Enzyme activity and PG concentrations receded to basal levels by 10.00 h on the day of estrus. These changes were prevented when the proestrous gonadotropin surge was blocked by administration of nembutal, and could be restored by administration of either LH or of FSH freed of LH contamination. The spontaneous preovulatory rise in prostaglandin concentration was about 6-fold for PGF and 30-fold for PGE, compared with values observed during the remainder of the cycle, whereas the rise in prostaglandin synthetase activity was only about 1.7-fold. The LH effect on PG accumulation had a latency of 2–4 h, which argues for enzyme synthesis rather than activation of preformed enzyme as the mechanism responsible. The small magnitude of the change in enzymic activity suggests that LH may, in addition, augment the availability of PG precursors. The results are compatible with the concept that prostaglandins play a physiological role in the gonadotropin-induced process of follicular rupture.