Prostaglandin Receptor Site: Evidence for an Essential Role in the Action of Luteinizing Hormone

Kuehl, Frederick A.; Humes, John L.; Tarnoff, J.; Cirillo, Vincent J.; Ham, Edward A.

doi:10.1126/science.169.3948.883

Cited by 257 publications

(70 citation statements)

References 12 publications

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“…Thus, it can be argued that inhibition of hormone action may be the actual response to prostaglandins in luteal cells rather than the mediation of LH action in mouse ovarian tissue suggested by Kuehl et al (11). In vlvo, the ovary is constantly exposed to LH and, in the absence of this gonadotropin, luteal progesterone production rapidly wanes (16 (3) and in cultures of porcine, bovine, and human luteinized granulosa cells exposed to PGF2o, for several hours (18 (2,6).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells

Thomas

Dorflinger

Behrman

1978

Proc. Natl. Acad. Sci. U.S.A.

112

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A reproducible method for dissociation and culture of rat luteal cells is described. The concentration of LH required to produce half-maximal stimulation of progesterone secretion was 50 ng/ml. The effects of prostaglandin E2 (PGE2) and prostaglandin F2(PGF2a)on basal and luteinizing hormone (LH) 1344 chorionic gonadotropin (hCG) by corpora lutea in vivo coincident with a decrease in circulating progesterone within 30 min. However, interpretation of these data was confounded by possible effects of PGF2a on blood flow because PGF2a was found to produce a similar effect on luteal accumulation of 15I-labeled prolactin (7).To further examine the interaction between PGF2a and LH on luteal progesterone production, it was deemed important to study the early and direct actions of these agents on luteal cells in vitro. The present studies describe the effect of PGE2 and PGF2c, on LH-dependent progesterone secretion in conjunction with studies on the effect of PGF2. on binding of gonadotropin to isolated luteal cells in culture. In this same model the effect of simultaneous incubation of luteal cells with LH, dibutyryl cyclic AMP [(Bt)2-cAMPJ,' and theophylline in the presence and absence of PGF2a!, in addition to the effect of PGF2 and LH on adenylate cyclase and cAMP accumulation, was examined to provide information on the possible site of action of prostaglandins.MATERIALS AND METHODS Animals. Immature (26-day-old) rats (CD strain, Charles River Laboratories, Wilmington, MA) were given a subcutaneous injection of 50 international units (IU) of pregnant mare serum (Gestyl, Organon) followed, 64 hr later, by a second subcutaneous injection of 25 IU of hCG (A.P.L., Ayerst).Dispersion of Luteal Cells. Ovaries were removed 7 days after hCG injection, and the cells were dispersed in Ca2+-free medium (medium 1) (no. 138, GIBCO, Grand Island, NY) containing 2000 IU of collagenase (Worthington, Freehold, NJ) and 3M00 IU of deoxyribonuclease (Worthington) per g of tissue for 1 hr at 370 under 95% 02/5% CO2. The contents of the flask were filtered through nylon mesh (Nyten, Tetko Inc.) and centrifuged (5 min, 100 X g); the supernatant fraction was discarded and the pellet was washed three times with fresh medium 1. The final cell concentration (106 cells per ml) was made up in minimal essential medium with 25 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonate buffer and Earles's salts (medium 2) (no. 236, GIBCO). Cell numbers were determined with a hemocytometer, and cell viability was tested by the trypan blue dye test (8

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Section: Discussionmentioning

confidence: 99%

Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells

Thomas

Dorflinger

Behrman

1978

Proc. Natl. Acad. Sci. U.S.A.

112

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“…[31][32][33][34] Earlier studies implicated AA as essential for growth and development, 35 but it is now recognized that AA is also extensively involved in brain signaling 36,37 via serotonergic, 38,39 glutamatergic, 40,41 dopaminergic 42,43 and cholinergic 44,45 receptor stimulation. AA and its derivatives are also ligands for several key transcriptional regulators, including peroxisomal proliferator activator receptors, 46 hepatic nuclear factor-4a, 47 prostaglandin receptors 48 and the liver X receptor, 49 collectively mediating numerous effects.…”

Section: Overview Of the Aa Cascadementioning

confidence: 99%

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

et al. 2008

Mol Psychiatry

108

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Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers (lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A 2 gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E 2 . Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease.

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“…1 C and D). Actions of PGs, where studied, have been shown to be mediated via a membranous receptor coupled to adenylate cyclase (20,21). The stimulatory effect of fMet-Leu-Phe on the human PMN is associated with a rapid rise in cyclic AMP levels (8) (Fig.…”

mentioning

confidence: 99%

Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils.

Ham¹,

Soderman²,

Zanetti³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

246

114

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Chemoattractant N-formylmethionylleucylphenylalanine (fMet-Leu-Phe) in the presence of cytochalasin B stimulates the release of leukotriene B4 (LTB4), superoxide (02) The influx and activation of neutrophils [PMN (polymorphonuclear leukocytes)] are essential for induction of inflammatory processes (1, 2). The chemoattractant N-formylmethionylleucylphenylalanine (fMet-Leu-Phe) and products of complement activation such as Ca recruit and activate the PMN to release active oxygen species and undergo degranulation (2,3). Such actions in concert with increased levels of prostaglandin E2 (PGE2) and prostacyclin (PGI2) lead to the cardinal symptoms of acute inflammation (3)(4)(5). Leukotriene B4 (LTB4), a product of the 5-lipoxygenase pathway, is itself a potent chemoattractant for PMN (6) and promotes their accumulation and adherence to the vascular endothelium proximal to the area of inflammation (3,7). Whether these actions of LTB4 supplement or mediate the effects of other chemoattractants remains unknown.Pharmacological levels of PGs inhibit superoxide (02) production induced by fMet-Leu-Phe in the presence of cytochalasin B (2) by an action purported to depend on increased cyclic AMP production (8). A similar cyclic AMP-dependent inhibition of lysosomal enzyme release has been observed by using large amounts of PGs (2, 8). Pharmacological levels of PGI2 (2.8 X 10-6 M) have also been reported to cause a partial inhibition (45%) of LTB4 release from human PMN activated with serum-treated zymosan (9).The studies in this report indicate that fMet- was obtained from J. Rokach (Merck Frosst) (10); MMM-I-135 (10,10-difluoro-13-dehydroprostacyclin) was a gift from J. Fried (University of Chicago) (11).The incubation buffer contained 130 mM NaCl, 5.5 mM KCl, 0.6 mM Na2HPO4, 0.6 mM NaH2PO4, 10 mM glucose, 1.0 mM CaC12, and 25 mM Tris HCl adjusted to pH 7.4 (12). Preparation of Cells. Rat PMN were obtained by peritoneal lavage with 40 ml of 0.9% NaCl/10 mM EDTA, pH 7.0, 16-24 hr after aseptic induction (13). PMN were recovered by centrifugation and the pellet was washed once in calcium-free incubation buffer, subjected to lysis buffer (14) for 5 min, rewashed in incubation buffer, and resuspended at a concentration of 5 x 106 cells per ml.Human peripheral PMN were isolated from fresh citrated human blood as described (15) and lysed as were the rat cells.Both preparations were >95% PMN.Incubation Conditions. Two-milliliter aliquots of PMN suspension were preincubated with calcium for 3 min at 37°C and then PGs or solvent was added for 5 min. Cytochalasin B (5 ,ug/ ml) was next added for 5 min, followed by addition of 10 ,uM fMet-Leu-Phe for 5 min. Dimethyl sulfoxide was at a final concentration of 0.7%. The incubations were terminated by centrifugation at 260 X g for 5 min at 0°C. The supernatants were analyzed for (5S)-5-hydroxy-6,8,11,14-icosatetraenoic acid (5-HETE), LTB4, and enzymes. Cell pellets were assayed for cyclic AMP.

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Prostaglandin Receptor Site: Evidence for an Essential Role in the Action of Luteinizing Hormone

Cited by 257 publications

References 12 publications

Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells

Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils.

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