Absence Of PGE Research Articles

THE PRINCIPAL GEOLOGICAL FEATURES OF THE MOOIHOEK PLATINIFEROUS DUNITE PIPE, EASTERN LIMB OF THE BUSHVELD COMPLEX, AND SIMILARITIES WITH REPLACED MERENSKY REEF AT THE AMANDELBULT MINE, SOUTH AFRICA

THE PRINCIPAL GEOLOGICAL FEATURES OF THE MOOIHOEK PLATINIFEROUS DUNITE PIPE, EASTERN LIMB OF THE BUSHVELD COMPLEX, AND SIMILARITIES WITH REPLACED MERENSKY REEF AT THE AMANDELBULT MINE, SOUTH AFRICA

Involvement of the constitutive prostaglandin E synthase cPGES/p23 in expression of an initial prostaglandin E 2 inactivating enzyme, 15-PGDH

We previously showed that cytosolic prostaglandin (PG) E synthase (cPGES/p23) which isomerizes PGH 2 to PGE 2, is essential for fetal mouse development. Embryonic fibroblasts derived from cPGES/p23 knockout mice generated higher amounts of PGE 2 in culture supernatants than wild-type-derived cells. In order to elucidate this apparent conflict that absence of PGE 2 synthetic enzyme caused facilitation of PGE 2 biosynthesis, we examined expression of the PGE 2 degrading enzyme in embryonic fibroblasts. We report here that embryonic fibroblasts deficient in cPGES/p23 decreased the expression of the PGE 2 degrading enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which catalyzes the inactivating conversion of the PGE 2 15-OH to a 15-keto group, compared with that of wild-type. In addition, rat fibroblastic 3Y1 cells harboring cPGES/p23 siRNA exhibited lower 15-PGDH expression than mock-transfected cells. Furthermore, forcible expression of cPGES/p23 in 3Y1 cells resulted in facilitation of 15-PGDH promoter activity. These results suggest that the PGE 2-inactivating pathway is controlled by the PGE 2 biosynthetic enzyme, cPGES/p23.

Involvement of the cytoskeleton in the effect of PGE 2 on ion transport in the rat distal colon

This work aimed at studying the effect of PGE 2 on water and chloride absorption from the rat distal colon and at investigating the involvement of the cytoskeleton in the modulation of colonic transporters. PGE 2 increased significantly net water and chloride absorption. It increased also the activity of the Na +K +-ATPase and the expression of the Na +K +2Cl − cotransporter. The increase in pump activity was ascribed to its phosphorylation by PKA or PKC when activated upon binding of PGE 2 to its receptors, and was deemed responsible for the increase in Cl − absorption. Cytochalasin B (CytoB), a disrupter of microfilaments, decreased net water and chloride absorption in presence or absence of PGE 2. Furthermore it down-regulated both pump and cotransporter, and lowered Na +K +-ATPase activity. It was suggested that an intact actin cytoskeleton is required for the basal and the PGE 2-elicited trafficking of both transporters. On the other hand, colchicine, an inhibitor of microtubule polymerization, had no effect on the absorption of water and chloride but abrogated the stimulatory effect of PGE 2. Colchicine exerted a similar effect to that of cytochlasin on the expression of both pump and cotransporter in presence or absence of PGE 2 except for the basal activity of the pump which was not altered by microtubule disruption. It was concluded that both microfilament and microtubular networks are involved in the basal and PGE 2-elicited increase in colonic ion absorption.

Interactions between NO, CO and an endothelium‐derived hyperpolarizing factor (EDHF) in maintaining patency of the ductus arteriosus in the mouse

Prenatal patency of ductus arteriosus is maintained by prostaglandin (PG) E(2), possibly along with nitric oxide (NO) and carbon monoxide (CO), and cyclooxygenase (COX) deletion upregulates NO. Here, we have examined enzyme source and action of NO for ductus patency and whether NO and CO are upregulated by deletion of, respectively, heme oxygenase 2 (HO-2) and COX1 or COX2. Experiments were performed in vitro and in vivo with wild-type and gene-deleted, near-term mouse fetuses. N(G)-nitro-L-arginine methyl ester (L-NAME) contracted the isolated ductus and its effect was reduced by eNOS, but not iNOS, deletion. L-NAME contraction was not modified by HO-2 deletion. Zinc protoporphyrin (ZnPP) also contracted the ductus, an action unaffected by deletion of either COX isoform. Bradykinin (BK) relaxed indomethacin-contracted ductus similarly in wild-type and eNOS-/- or iNOS-/-. BK relaxation was suppressed by either L-NAME or ZnPP. However, it reappeared with combined L-NAME and ZnPP to subside again with K(+) increase or K(+) channel inhibition. In vivo, the ductus was patent in wild-type and NOS-deleted fetuses. Likewise, no genotype-related difference was noted in postnatal closure. NO, formed mainly via eNOS, regulates ductal tone. NO and CO cooperatively mediate BK-induced relaxation in the absence of PGE(2). However, in the absence of PGE(2), NO and CO, BK induces a relaxant substance behaving as an endothelium-derived hyperpolarizing factor. Ductus patency is, therefore, sustained by a cohort of agents with PGE(2) and NO being preferentially coupled for reciprocal compensation.

Below the Speed Limit in the Absence of PGE 2

Prostaglandins had been implicated in early development, and in zebrafish loss of cyclooxygenase 1 (COX-1) caused gastrulation defects. Cha et al. now show that signaling mediated by the production of prostaglandin E 2 (PGE 2 ) is responsible for the embryonic defects. Transcripts for PGE 2 synthase (Ptges in zebrafish) and COX-1 were expressed at the same time and places during gastrulation. Furthermore, PGE 2 was detected by mass spectrometry during gastrulation. Injection of antisense morpholino oligonucleotides against Ptges caused gastrulation defects consistent with aberrant cell movement without affecting patterning or cell fate specification (based on marker analysis). Only exogenous PGE 2 , not PGI 2 or PGF 2α , rescued the Ptges-deficient embryos. Sequence searching revealed two candidate zebrafish PGE 2 receptors, EP2 and EP4, of which only EP4 was present during gastrulation. Injection of antisense morpholino oligonucleotides against EP4 caused gastrulation defects like those observed for loss of COX-1 or Ptges. Time-lapse microscopy revealed that the EP4-deficient cells moved more slowly, but in the proper direction. Finally, analysis of the phosphorylation state of Akt and extracellular signal-regulated kinase (ERK) indicated that EP4 was coupled to a phosphoinositide 3-kinase (PI3K) to Akt pathway. Thus, PGE 2 appears to play an essential permissive role in gastrulation through its effects on cell migration. Y. I. Cha, S.-H. Kim, D. Sepich, F. G. Buchanan, L. Solnica-Krezel, R. N. DuBois, Cyclooxygenase-1-derived PGE 2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation. Genes Dev. 20 , 77-86 (2006). [Abstract] [Full Text]

Immunomodulatory activity of TNF-α during acute liver injury induced by d-galactosamine and its protection by PGE 1 in rats

Tumour necrosis factor-α (TNF-α) mediates hepatocyte cell death by d-galactosamine ( d-GalN) and its protection by prostaglandin E 1 (PGE 1). The activation of immune system plays an important role in the development of liver injury. TNF-α and PGE 1 regulate the activity and cytokine release of different inflammatory cells. The present study was undertaken to determine if the noxious or hepatic protective properties of TNF-α during d-GalN-induced liver injury was related to an alteration by PGE 1 of the immunoregulatory activity of TNF-α. The role of TNF-α was assessed by anti-TNF-α antibodies to d-GalN-treated rats in the presence or absence of PGE 1. d-GalN enhanced the percentage of monocytes and T lymphocytes in the total peripheral blood mononuclear cells (PBMCs). d-GalN enhanced the activation degree of monocytes, but reduced that of T lymphocytes. d-GalN also enhanced TNF-α, IL-1α, IL-6 and IFN-γ concentrations in blood. Anti-TNF-α antibodies abolished all immunological changes and greatly reduced liver damage induced by d-GalN. The protection by PGE 1 against d-GalN liver injury was associated with an increase in TNF-α concentration and a reduction of IL-1α and IL-6. These changes were associated with a reduction of monocyte activation degree and a recovery of that of T lymphocytes. Although anti-TNF-α antibodies abolished the protection by PGE 1 against d-GalN-liver injury, they did not essentially counteract the effect of the prostanoid in all immunological parameters studied. The present study showed that the protection against d-GalN liver damage by PGE 1 or anti-TNF-α was associated with similar effects on the inflammatory parameters studied. Nevertheless, the abolishment of liver protection by PGE 1 with anti-TNF-α in d-GalN-treated rats in the presence of a protective cytokine profile suggests that the release of TNF-α induced by PGE 1 pre-administration was exerting a direct protective effect on hepatocytes against d-GalN injury. Consequently, the effect of PGE 1 on inflammatory parameters studied during liver injury was unrelated to TNF-α.

The role of PGE(2) in the differentiation of dendritic cells: how do dendritic cells influence T-cell polarization and chemokine receptor expression?

The role of prostaglandin E(2) (PGE(2)) in the function of dendritic cells (DCs), T-cell polarization, and expression of chemokine receptors was evaluated in human cells. Immature DCs were generated from peripheral blood CD14(+) cells using a combination of GM-CSF and interleukin-4 (IL-4) with or without PGE(2). On day 6, maturation of DCs was induced by the addition of tumor necrosis factor alpha with or without PGE(2). DCs harvested on day 6 (immature DCs) or day 9 (mature DCs) were examined using functional assays. In the presence of PGE(2), immature and mature DCs showed, phenotypically, a lower expression of CD1a and, functionally, a higher allostimulatory capacity at a high DC/T-cell ratio than control cells cultured in the absence of PGE(2). DCs cultured in the presence of PGE(2) induced the differentiation of naïve T cells toward a helper T-cell type 1 (Th1) response, which was independent of IL-12 secretion in the basal state despite a slightly lower interferon gamma secretion compared with control cells. However, the function of cytotoxicity-stimulating autologous T cells was not augmented by the addition of PGE(2). Immature DCs expressed the inflammatory chemokine receptors, CCR1 and CXCR4, but not CCR6, regardless of the presence or absence of PGE(2). Mature DCs expressed CCR7 equally, measured using a migration test and the measurement of calcium flux with macrophage inflammatory protein-3beta and reverse transcription-polymerase chain reaction assay in all of the groups. All of these findings suggest that PGE(2) affects the DC-promoted differentiation of naïve T cells to a Th1 response in the basal state, without affecting chemokine receptor expression on DCs.

Resolution of inflammation

Acute inflammatory reactions, in contrast to chronic inflammatory reactions, are usually self-limiting and resolve. We have investigated the resolving phase of a number of immune and non-immune inflammatory reactions induced in the pleural cavity of rats. COX-2 is expressed during resolution of these models. Using carrageenan pleurisy, we showed that this enzyme has a proinflammatory role as the reaction develops but an antiinflammatory role as the lesion resolves. This antiinflammatory role is associated with production of cyclopentenone prostaglandins and the absence of PGE 2. Dual COX-1/COX-2 inhibitors or COX-2 inhibitors when given at the peak of the inflammatory response delay resolution, an effect reversed by replacing CyPGs into the pleural space. PGF 2α like the CyPGs appears to have a role in resolving this reaction. Stress proteins are also induced in a variety of acute inflammatory models during resolution. Heme oxygenase-1 (HO-1) is one such protein so too are members of the hsp70 family. An inducer of HO-1 promotes resolution whereas an inhibitor is proinflammatory. In most cases it appears to be the macrophage that is the source of proteins necessary for resolution to occur. Understanding how proinflammatory pathways switch to the antiinflammatory pathways necessary for resolution to take place may eventually allow the exploitation of endogenous antiinflammatory pathways in the treatment of chronic inflammation.

Prostaglandin E 2 activation of VIP secretomotor neurons in the guinea pig ileum

The effect of prostaglandin E 2 (PGE 2) on the activity-related expression of the proto-oncogene c-fos in specific populations of enteric neurons was investigated. Segments of guinea-pig ileum were incubated in vitro in the presence or absence of PGE 2, and whole mounts of the myenteric and submucosal plexus were prepared for immunocytochemical localization of Fos, VIP and NPY. Control tissues exhibited a low number of Fos-immunoreactive (Fos-IR) neurons (7±2% of total). Incubation of the tissues with 10–1000 nM PGE 2 for 30 min caused a concentration-dependent increase in Fos-IR submucosal neurons (maximum at 100 nM; 39±6%), which was not inhibited by TTX. PGE 2 did not evoke an increase in Fos-IR myenteric neurons. In double labeling experiments, Fos colocalized exclusively with VIP in the submucosal plexus, and not with NPY. Exposure of stripped segments of guinea pig ileum in Ussing chambers to 100 nM PGE 2 evoked an increase in short circuit current (20±7 μA/cm 2), of which the initial rapid phase could be abolished by TTX, and not by atropine and hexamethonium. It is concluded that PGE 2 can activate VIP non-cholinergic secretomotor neurons.

The effect of prostaglandin E 2 and indomethacin on the cytotoxic response to mycobacterial antigens

The effect of prostaglandin E 2 and indomethacin on the generation of cytotoxic T-lymphocytes in response to Mycobacterium tuberculosis (MTB) antigens was compared between healthy controls and rheumatoid arthritis patients. Peripheral blood mononuclear cells (PBMC) from 16 healthy individuals and 15 RA patients were stimulated for 7 days with an irradiated, sonicated preparation of MTB in the presence or absence of PGE 2 or indomethacin and assayed for cytotoxic activity on autologous target cells prepulsed with MTB. The mean cytotoxic activity generated was lower in patients than in controls. Exogenous PGE 2 suppressed the cytotoxicity directed against MTB pulsed targets in 12 of 16 controls, but in only 1 of 11 patients. Indomethacin enhanced this cytotoxicity in only 2 of 16 controls but in 6 of 10 RA patients. When effector cells were derived from the synovial fluid, PGE 2 again had no effect and indomethacin enhanced the cytotoxicity. Our data suggest that the depressed cytotoxic response of RA patients to MTB may be due to the production of endogenous PGE 2. Cyclooxygenase inhibitors commonly used in the treatment of RA may influence MTB induced cytotoxicity in patients. In addition to their anti-inflammatory effects within the joint, non-steroidal anti-inflammatory drugs may potentially enhance cytotoxic reactions which are induced by antigens, such as MTB cross-reactive heat shock proteins.

Responsiveness of Murine Lymphokine-Activated Killer Activity to Prostaglandin E<sub>2</sub> at Late Phase of lnterleukin-2 Induction

To elucidate the inhibitory effect of prostaglandin E2 (PGE2) on the generation of recombinant interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) activity, we have examined the association between cellular 3',5'-cyclic adenosine monophosphate (cAMP) and cytolytic activity of 3-day IL-2-cultured murine LAK cells, i.e. at late phase of IL-2 induction, in the presence and absence of PGE2. The results indicate that, at the late phase of IL-2 induction, LAK cells retain their responsiveness to PGE2 inhibition, and the inhibition can be partially suppressed by additional IL-2 in proportion to the decrease in the ratios of stimulated to basal cellular cAMP levels.

Effect of prostaglandin E 2 on cyclic AMP levels in limb cells of mouse mutant Brachypodism

Mouse embryo limb cells carrying either the brachypodism ( bp H/bp H ) mutation or its wild-type (+/+) allele were tested for their ability to accumulate cyclic AMP in response to prostaglandin E 2 (PGE 2) between Embryonic Days E12 and E14. Mutant cells exhibited a precocious increase in cyclic AMP. In the absence of PGE 2 but in the presence of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (MIX), the brachypodism cells accumulated a significantly lower amount of cyclic AMP by Day E14. Limb cells carrying the bp H mutation may provide a useful experimental system to study the PGE 2-cyclic AMP-cartilage differentiation interrelationship.

Inhibition of human NK cell and LAK cell cytotoxicity and differentiation by PGE 2

Activation of natural killer (NK) activity against K562 target cells from nonadherent (NA) lymphocytes by interleukin 2 (IL-2) was inhibited marginally by PGE 2 (30–3000 n M). PGE 2 did not effectively suppress the NK activity of IL-2-activated cells. The NK activation and acquisition of resistance to PGE 2-mediated suppression of NK activity were dependent on protein synthesis. When NA cells were incubated with IL-2 for 3 or more days to generate lymphokineactivated killer (LAK) activity against Raji target cells, PGE 2 only partially inhibited the activation of NK/LAK activity by an optimal dose of IL-2 (10 U/ml). The activation of NK/LAK activity by a suboptimal dose of IL-2 (0.1 U/ml) was inhibited by PGE 2. When the NK/LAK activity of IL-2-activated cells was assessed in the presence or absence of PGE 2, the LAK activity was more sensitive than the NK activity to PGE 2-mediated suppression.

Thermal decomposition behavior of bis‐aminimides and their application to polymerization of epoxide

AbstractBis‐aminimide compounds [bis‐N, N,‐dimethyl‐N,‐(2‐hydroxypropyl)‐amine‐N,′‐adipimide (1) and bis‐trimethylamine adipimide (2)] were found to exhibit different thermal decomposition behavior and polymerization efficiency for an epoxide (phenyl glycidyl ether, PGE). The thermal decomposition rate of 1 was much higher than that of 2. It seemed that hydrogen bonding enhanced the decomposition rate. Compound 1 was thermolyzed to give a diisocyanate and a tertiary aminoalcohol, which subsequently reacted with each other to give a urethane. When 2 was heated, the isocyanate generated from 2 remained unreacted. PGE reacted with thoseaminimides to give different products, depending on their thermolyzed products. Mixtures of diisocyanate, tertiary amine, and PGE were used in the model reactions, and the thermal reaction between the expected decomposition products of aminimides was investigated in the presence and absence of PGE. The amount of high molecular weight fraction in PGE + 2 is greater than that of PGE + 1. In the former, the free isocyanate groups may act as a chain extender to give higher molecular weight fractions.

Thermal decomposition behavior of mono‐aminimides and their application to polymerization of epoxide

AbstractMono‐aminimide compounds [N,N‐dimethyl‐N‐(2‐hydroxypropyl)‐amine‐N′‐propionimide (1), trimethylamine valerimide (2), and trimethylamine benzimide (3)] were found to exhibit different thermal decomposition behaviors and polymerization efficiencies for an epoxide (phenyl glycidyl ether, PGE). The thermal decomposition rate of aminimides at 150°C decreased in the order 1 > 2 > 3. It seemed that hydrogen bonding enchanced the decomposition rate, and the resonance effect induced by the phenyl group suppressed the decomposition. 1 was thermolyzed to give isocyanate and tertiary aminoalcohol, which subsequently reacted with each other to give isocyanate and tertiary aminoalcohol, which subsequently reacted with each other to give urethane. When 2 was heatted, the isocyanurate generated from 2 remained intact. On heating of 3, we observed the formation of triphenyl isocyanurate. PGE reacted with those aminimides and gave different products depending on their thermolyzed products. Equimolar mixtures of isocyanate, tertiary amine, PGE were used in the model reactions, and the thermal reaction between the expected decompostion products of aminimides was investigated in the presence and absence of PGE. The rate of PGE consumption was in the order PGE + 2 > PGE + 1 > PGE + 3. It is clear that the formation of urethanes and oxazolidone derivatives affects the polymerization process.

Collagen synthesis inhibition by PGE 2 within the human follicular wall — One possible mechanism underlying ovulation

Follicular wall specimens were taken from various parts of human preovulatory follicles as well as from less developed follicles. The tunica albuginea was isolated and incubated for 2 h in Krebs Ringer bicarbonate buffer containing 3H-proline in the presence or absence of PGE 2 (0.1 μg/ml). Following incubation the incorporated radioactivity was determined and related to the protein content of each strip. PGE 2 had a specific effect on the incorporation of 3H-proline into protein in the follicular wall. In the apical part of the preovulatory follicle a significantly decreased incorporation was registered, indicating a reduced net synthesis of collagen. However, PGE 2 was without effect on specimens derived from the non-apical parts of the preovulatory follicles as well as from the less developed follicles. It is suggested that the registered biochemical changes induced by PGE 2 are of importance for the process of human ovulation.

Modulation on neuromuscular transmission by endogenous and exogenous prostaglandins in the guinea-pig mesenteric artery.

1. At concentrations of 2.8 x 10(-8)-2.8 x 10(-6) M, prostaglandins (PGs; PGE(1), PGE(2) and PGF(2alpha)) had no effect on membrane potential and resistance of smooth muscles of the guinea-pig mesenteric artery. PGs (2.8 x 10(-8) M) suppressed the contraction evoked by perivascular nerve stimulation, but did not suppress the contraction evoked by direct muscle stimulation.2. PGs (2.8 x 10(-8) M) suppressed the e.j.p.s evoked by repetitive perivascular nerve stimulation but preserved the facilitation process of e.j.p.s evoked by any given stimulus frequency (0.1-1.0 Hz).3. The relationships between e.j.p. amplitudes and [Ca](o) plotted on log scales in the presence or absence of PGE(2) were not parallel. High concentrations of [Ca](o) prevented the inhibitory actions of PGs on the amplitude of e.j.p.s.4. PGE(2) did not suppress the activity of nerve fibres contributing to the generation of e.j.p.5. Indomethacin (10(-6) M) enhanced the amplitude of e.j.p.s and the frequency of miniature e.j.p.s with no change in the membrane potential and resistance of smooth muscles; these actions of indomethacin were suppressed by PGE(2) (2.8 x 10(-8) M).6. Phentolamine (10(-7) M) enlarged and yohimbine (10(-7) M) reduced the amplitude of the first e.j.p. evoked by a train stimulation, but the maximum amplitude of e.j.p., after the facilitation was completed, was in both cases much larger than that observed in the control. The enhancement of the transmission process was also suppressed by PGs (2.8 x 10(-8) M).7. The results indicate that in the guinea-pig mesenteric artery, PGs mainly suppress chemical transmitter release from nerve terminals due to interactions with Ca influx, but not due to interaction with presynaptic alpha-adrenoceptors. Endogenous PG may act as a regulator substance in neuromuscular transmission.

Effect of a prostaglandin antagonist, N-0164, on cAMP generation and hydrolysis in the rat uterus

N-0164 (sodium- p-benzyl-4-[1-oxo-2-(4-chlorobenzyl)-3-phenyl propyl] phenylphosphonate) (20–100 μM), an antagonist of the contractile effect of prostaglandins, reversed the prostaglandin E 2 (PGE 2) inhibition of isoproterenol-induced cAMP accumulation in rat uterus. N-0164, at the same concentrations, was a potent cAMP-phosphodiesterase inhibitor in broken cell preparations and potentiated the cAMP response to isoproterenol in intact tissue. The potency of N-0164 to inhibit cAMP-phosphodiesterase and to reverse the effect of PGE 2 on the cAMP response to isoproterenol were comparable ( ec 50 :50 and 60 μM respectively). In the presence of 10 mM theophylline, N-0164 did not affect the inhibitory effect of PGE 2. Furthermore, N-0164 produced similar proportional increases in the cAMP response to isoproterenol in the presence and absence of PGE 2. These results suggest that the apparent reversal by N-0164 of the PGE 2 effect on the cAMP response to isoproterenol is not due to its prostaglandin antagonistic action but to inhibition of cAMP-phosphodiesterase. N-0164, at concentrations lower than those inhibiting cAMP-phosphodiesterase, selectively inhibited the PGE 2-induced contractions of the rat uterus ( ec 50, 4 μM), while at higher concentrations it also diminished carbachol-induced contractions. These results indicate that in the rat uterus N-0164 has at least two effects, prostaglandin antagonism and cAMP-phosphodiesterase inhibition, and suggest that the contractile effect of PGE 2 is independent of the effect of PGE 2 on the isoproterenol-induced rise in cAMP.

Angina-like pain: An unexpected side-effect following the simultaneous administration of angiotensin II and prostaglandin E 2 in normal adults

Two fit young, non-pregnant adults both experienced marked retrosternal chest pain and chest tightness when receiving 8 ng kg −1 min −1 AII simultaneously with 5 μg min −1 PGE 2. This dose of AII is well within that given experimentally by various workers, and was without such effect when initially given in the absence of PGE 2 infusion. The combination may therefore be a potentially dangerous one.

Prostaglandin E 2-induced lordosis in estrogen-primed female hamsters: Relationship to progesterone action

Intraperitoneal injection of 10, 50, 100 or 250 μg of prostaglandin E 2 (PGE 2) resulted in a dose-dependent facilitation of lordosis in ovariectomized female hamsters given estradiol-17β in silastic capsules 72 hr earlier. The ability of progesterone to facilitate lordosis in the absence of PGE 2 mediation was investigated by injecting ovariectomized, estrogen-primed females with indomethacin, a prostaglandin synthesis inhibitor, at 1.5 hr before and after progesterone administration. Conversely, the ability of PGE 2 to facilitate receptivity independently of progesterone mediation was examined by injecting 100 μg or 250 μg PGE 2 to estrogen-primed, ovariectomized-adrenalectomized females. Because indomethacin did not interfere with progesterone-induced lordosis, and because PGE 2-induced lordosis was not abolished by adrenalectomy, it was concluded that induction of lordosis by progesterone and PGE 2 are mutually independent processes. A final study investigated the ability of PGE 2 to facilitate lordosis during the period of progesterone-induced inhibition of receptivity. When compared to PGE 2-treated controls, the administration of 200 μg progesterone 24 hr prior to 100 μg PGE 2 injection significantly reduced the proportion of ovariectomized estrogen-primed females who exhibited lordosis. These results are consistent with the view that progesterone inhibits lordosis via some general mechanism such as interference with the estrogen priming process.