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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the effects of arachidonic acid (AA) and some of its metabolites on progesterone (P4) and oxytocin (OT) release by corpora lutea obtained from Holstein heifers at day 8 of the estrous cycle (Day 0 = estrus). The luteal cells were dispersed with collagenase and small and large cells were separated by unit gravity sedimentation and flow cytometry. After an 18-hr preincubation period, the cells were incubated in the presence of various treatments for 1 hr, followed by a 23-hr incubation period with no treatment. OT was secreted by the large, but not by the small, luteal cells into the incubation medium. AA elicited a significant (P less than 0.05) release of OT from the large cells and P4 from both the large and small cells within 1 hr of incubation, having a specific effect at a concentration of 10 microM. Larger doses (25 and 100 microM) of AA adversely affected the cell viability. Phospholipases A2 (0.5 unit/ml) and C (0.05 unit/ml) and calcium ionophore A23187 (0.1 microM) stimulated OT release from the large cells to the same extent as AA (10 microM). Inhibition of the AA cyclooxygenase metabolic pathway by indomethacin did not affect AA-induced release of OT and P4, although exogenous prostaglandins F2 alpha and I2 (5-25 ng/ml) stimulated the release of OT. Lipoxygenase products of AA (hydroxyeicosatetraenoic acid and leukotrienes; 25 ng/ml) also stimulated OT release. Inhibition of the lipoxygenase metabolic pathway by nordihydroguaiaretic acid abolished AA-induced release of both OT and P4. These results suggest that intracellular accumulation of free AA may modulate secretory functions in the bovine corpora lutea, including OT and P4 release.
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PMID:Role of arachidonic acid and its metabolites in the regulation of progesterone and oxytocin release from the bovine corpus luteum. 152 4

We have recently demonstrated that corticotropin releasing hormone (CRH) potentiates the contractile response to oxytocin of human gestational myometrium, using a high flow microsuperfusion system and electrical field stimulation. We now report this potentiation to be equivalent to that of 1 nM prostaglandin F2 alpha (PGF2 alpha), while 10 nM PGF2 alpha did not potentiate the response to oxytocin. Prostaglandin E2 (PGE2) also showed no augmentation of the contraction force of the myometrium in response to oxytocin. The CRH potentiated response was inhibited by the lipoxygenase and cyclooxygenase inhibitor BW755C (1 microM) and by indomethacin (0.1 microM), but not by the lipoxygenase inhibitor BW4C (1 microM). Measurements of prostaglandins in the superfusate showed no significant trends. It is concluded that the potentiation of contraction force to oxytocin by CRH is dependent on prostaglandins, probably PGF2 alpha and that leukotrienes, generated via the lipoxygenase pathway are not involved.
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PMID:Role of prostaglandins and leukotrienes in the synergistic effect of oxytocin and corticotropin-releasing hormone (CRH) on the contraction force in human gestational myometrium. 177 36

1. Effects of atrial natriuretic peptide (ANP) on tension development, particulate guanylate cyclase activity and guanosine 3':5'-cyclic monophosphate (cyclic GMP) concentrations of uteri from oestrogen-treated, progesterone-treated, ovariectomized and pregnant rats were determined in vitro. 2. ANP inhibited the tension development by myometrial tissues from oestrogen-treated virgin rats and the sterile horn of 10 to 14 day pregnant rats but not of the uterus from pregnant and progesterone-treated rats. 3. Inhibition of cyclo-oxygenase and lipoxygenase activities did not restore the tocolytic activity of ANP on gravid uterus. ANP exerted a tocolytic effect on nongravid uterus submaximally stimulated by prostaglandin F2 alpha (PGF2 alpha), oxytocin, vasopressin, angiotensin II or 5-hydroxytryptamine (5-HT). 4. Ovariectomy decreased the tocolytic effects of ANP, which could be restored by oestrogen treatment. 5. The refractoriness to the tocolytic effect of ANP in pregnant rats was not accompanied by a decrease in its relaxant effects on isolated aortic strips. 6. Tocolytic effects of isoprenaline, isobutylmethyl xanthine and hydroxylamine were not influenced by pregnancy or progesterone treatment. Up to a concentration of 3 mM, sodium nitroprusside did not affect myometrial tension development. 7. Pregnancy and progesterone treatment markedly inhibited ANP-induced increases in myometrial particulate guanylate cyclase activity and cyclic GMP concentrations but did not influence the effects of ANP on aortic cyclic GMP concentrations. 8. It is concluded that exposure of the myometrium to circulating and placentally-produced progesterone is responsible for the pregnancy-induced decrease in the effects of ANP on myometrial particulate guanylate cyclase activity and cyclic GMP concentrations and in turn on myometrial tension development.
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PMID:Refractoriness of the gravid rat uterus to tocolytic and biochemical effects of atrial natriuretic peptide. 197 61

Two experiments were conducted to determine if intrauterine infusion of nordihydroguaiaretic acid, a lipoxygenase pathway inhibitor, would delay luteolysis (Experiment 1) and inhibit oxytocin-induced release of prostaglandin F2 alpha (as measured by the stable prostaglandin F2 alpha metabolite, 15-keto-13,14-dihydroprostaglandin F2 alpha) in plasma on d 16 (d 0 = estrus) of the estrous cycle (Experiment 2). Nordihydroguaiaretic acid (20 mg) or saline was infused twice daily into the uterus on d 14 to 23 (Experiment 1) or d 14 to 20 (Experiment 2) postestrus, respectively. In Experiment 1 and 2, mean concentration of progesterone was higher and luteolysis was delayed in nordihydroguaiaretic acid-infused heifers compared with saline-infused heifers. In Experiment 2, saline or oxytocin (100 IU, i.v.) was injected into each heifer on d 16 postestrus to stimulate the release of prostaglandin F2 alpha from the uterus. Mean concentration of 15-keto-13,14-dihydroprostaglandin F2 alpha increased within 1.5 h postinjection in heifers infused with saline, whereas concentration of 15-keto-13,14-dihydroprostaglandin F2 alpha in nordihydroguaiaretic acid-infused heifers did not increase within the same time period. Thus, nordihydroguaiaretic acid may inhibit both the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism and therefore delay luteolysis.
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PMID:Effect of nordihydroguaiaretic acid on luteal phase length and oxytocin-induced release of prostaglandin F2 alpha in heifers. 225 84

Indomethacin and substance BW-755C in experiments on isolated myometrium striae of pregnant white rats exert an inhibiting effect on the contractile uterus function due to inhibition of cyclooxygenase or lipoxygenase ways of the arachidonic acid transformation. Prostaglandin F2 alpha is sensitive to functioning of the cyclooxygenase and lipoxygenase ways of the arachidonic acid transformation, while oxytocin--only lipoxygenase one. Conclusions rest on results from multiparametric analysis of the contractile uterus function suggested by authors and confirmed by the pattern recognition method--the Karunen-Loev orthogonal decomposition.
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PMID:[Comparative evaluation of the action of prostanoid inhibitors on uterine contractile function]. 250 61

We examined the relation between increased uterine oxytocin receptor concentration and increased in vivo sensitivity of the rabbit uterus to oxytocin at the end of gestation. We determined oxytocin receptor concentrations in myometrium and decidua on different days near term of gestation and postpartum. We also examined the in vitro contractile response to oxytocin on days 30 and 5 days postpartum, when the uterus is unresponsive in vivo, and on day 31 (term), when the uterus is exquisitely sensitive to this hormone in vivo. In addition, we tested the role of endogenous eicosanoids and decidual oxytocin receptors in the myometrial contractile response to oxytocin by examining the contractile response in the presence of the cyclooxygenase/lipoxygenase inhibitor sodium meclofenamate or in muscle strips from which the decidua had been removed by scraping. The concentration of specific binding sites for [3H]oxytocin in myometrial and also decidual membrane preparations was determined. We demonstrate that contractile sensitivity to oxytocin increases at least 4-fold between days 30 and 31 (term) of gestation, and this is accompanied by a nearly 10-fold increase in the concentration of oxytocin-binding sites in both decidua and myometrium. The lesser sensitivity to oxytocin on day 30 was, however, only apparent in the presence of meclofenamate, which suggests that endogenous eicosanoids contribute to the preterm response to oxytocin measured in vitro. The maximal response to oxytocin (integrated area) increased 2-fold between day 30 and term. Thus, an increase in both sensitivity and maximal response to oxytocin could be demonstrated at term in vitro. Five days after parturition, maximal response and uterine sensitivity measured in the presence of meclofenamate had returned to those of the preterm uterus, and the concentration of oxytocin-binding sites had declined. In contrast, sensitivity and maximal response to the cholinergic agonist carbamylcholine declined between day 30 and term. These results support a highly regulated physiological role for oxytocin in parturition which depends primarily on changes in receptor concentration.
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PMID:Rabbit uterine oxytocin receptors and in vitro contractile response: abrupt changes at term and the role of eicosanoids. 301 54

Five new concepts concerning the control of corpus luteum function in the cow have been developed in recent years. Prostacyclin (PGI-2) plays a luteotrophic role. Conversely, products of the lipoxygenase pathway of arachidonic acid metabolism, particularly 5 hydroxyeicosatetraenoic acid (5-HETE), play luteolytic roles. Luteal cells arise from two sources. The small luteal cells are all of theca cell origin; the large cells found early in the cycle (Days 2-6) are mainly of granulosa cell origin. However, a population of large cells found after Day 10 of the cycle are of theca cell origin. Oxytocin of luteal cell origin plays a role in development of the corpus luteum and possibly in its regression. The recently described Ca2+-polyphosphoinositol-protein kinase C second messenger system, as well as the LH-cAMP system, is involved in control of progesterone synthesis in the bovine corpus luteum. Progesterone synthesis in the small theca-derived luteal cells is primarily controlled by the cAMP system. However, elevated intracellular calcium diminishes cAMP-mediated progesterone synthesis in these cells. These findings modify our current concepts of the mechanisms of control of progesterone secretion by the corpus luteum and suggest several new lines of research.
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PMID:Hammond memorial lecture. New concepts of the control of corpus luteum function. 302 24

Oxytocin (50-750 nM) contracted the isolated testicular capsule of the rat. Mepacrine, a phospholipase A2 inhibitor (3 X 10(-5) M) and the lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) M) inhibited this response whereas the cyclooxygenase inhibitor, diclofenac sodium (10(-5) M), and the thromboxane synthetase inhibitor imidazole (10(-5) M) did not. It appears that metabolites of arachidonic acid dependent on lipoxygenase are involved in the contractile response of the rat testicular capsule to oxytocin.
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PMID:Influence of some inhibitors of arachidonic acid metabolism on oxytocin contractions in the isolated testicular capsule of the rat. 310 57

The involvement of arachidonic acid and arachidonic acid metabolites in the control of oxytocin secretion by ovine corpus luteum was investigated, using slices of luteal tissue incubated in vitro. Oxytocin was secreted at steady rates by luteal slices, during 60-min incubations (315.0 +/- 45.3 pg/mg.h). The secretion of oxytocin was stimulated by arachidonic acid, phospholipase A2 (PLA2), and phospholipase C (PLC) in a dose-dependent manner. The highest doses of arachidonic acid, PLA2, and PLC used stimulated oxytocin secretion by 145.8 +/- 23.0% (P less than 0.01; n = 6), 331.5 +/- 42.4% (P less than 0.02; n = 4), and 955.5 +/- 278.6% (P less than 0.01; n = 4), respectively. Oxytocin secretion by luteal slices was not affected by either prostaglandin F2 alpha (PGF2 alpha) or PGE2 over a concentration range from 3-3000 nM. Furthermore, inhibitors of the cyclo-oxygenase pathway of arachidonic acid metabolism did not consistently affect arachidonic acid and PLA2-stimulated oxytocin secretion. Nordihydroguaiaretic acid, which inhibits 5-lipoxygenase, however, totally abolished arachidonic acid- and reduced PLA2-stimulated oxytocin secretion. The presence of CoCl2 in the incubation medium also significantly reduced basal and PLA2- and PLC-stimulated oxytocin secretion [P less than 0.05 (n = 5), P less than 0.05 (n = 5), and P less than 0.01 (n = 6), respectively]. We have shown that oxytocin secretion from slices of ovine corpus luteum incubated in vitro is stimulated by exogenous and endogenously released arachidonic acid. The data show that PGF2 alpha and PGE2 do not have a role in luteal oxytocin secretion in vitro and PG formation does not appear to be involved in the stimulation of oxytocin secretion elicited by arachidonic acid or PLA2. Arachidonic acid may have its effect via the lipoxygenase pathway.
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PMID:Control of oxytocin secretion by ovine corpora lutea: effects of arachidonic acid, phospholipases, and prostaglandins. 312 41

Normal corpus luteum function is determined by function in the follicular as well as the luteal phase. In the follicular phase adequate follicle-stimulating hormone (FSH) and oestrogen stimulation are required for granulosa cell mitosis and luteinizing hormone (LH) receptor synthesis. An increase in LH pulse frequency may also be necessary for adequate oestrogen synthesis and preparation of follicular cells for luteinization and secretion of progesterone. The nature of LH release may also influence luteal function and pre-ovulatory progesterone may increase the responsiveness of the follicle to gonadotrophins. The thecal vascular network becomes extensive around pre-ovulatory follicles and may influence access of gonadotrophins and/or the ability of follicular cells to respond to them. Further vascularization is an early feature of luteinization. Angiogenic factors are found in luteal tissue and prostacyclin increases luteal blood flow. The corpus luteum consists of large cells which secrete most of the progesterone and have prostaglandin F2 alpha receptors and small cells which are responsive to LH. In the luteal phase subnormal luteal function has not been associated with a reduction in LH concentration, pulse frequency or amplitude. The number and occupancy of LH receptors and adenylate cyclase activity do not appear to be altered by a reduction in luteal function. Low density lipoprotein provides the substrate and somatomedin C modulates among other hormones' influences, progesterone production. In addition to the cAMP second messenger system phosphatidyl inositol metabolism may also be associated with LH stimulation. Luteolysis is an active process; prostaglandin F2 alpha or lipoxygenase products and possibly an endogenous GnRH-like ovarian hormone may mediate it as also may oxytocin in some species.
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PMID:The corpus luteum. 328 62


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