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

This study was conducted to determine whether early progesterone treatment plays a role in the regulation of messenger RNA (mRNA) expression for oxytocin-neurophysin, oxytocin receptor, prostaglandin G/H synthase (PGHS)-1 and PGHS-2 in the ovine corpus luteum. The expression of ovarian oxytocin, oxytocin receptor, PGHS-1 and PGHS-2 mRNA was investigated in control, progesterone- or RU486-treated ewes. Fifteen ewes were randomly assigned to three groups to receive intramuscular injections of progesterone (12.5 mg; n = 5), RU486, (2.5 mg kg(-1) bodyweight; n = 4) or corn oil (1 mL; n = 6) twice daily from Day 1 to Day 3 post oestrus. On the morning of Day 4 post oestrus, the corpora lutea were collected and analysed for oxytocin-neurophysin mRNA by Northern blot using a labelled cDNA probe, and for the expressions of the oxytocin receptor, PGHS-1 and PGHS-2 mRNA using the reverse transcription polymerase chain reaction. Administration of progesterone or suppression of progesterone activity with RU486 did not affect expression of oxytocin-neurophysin mRNA (P>0.05). Pretreatment of the ewes with progesterone resulted in the enhancement of luteal oxytocin receptor mRNA expression and suppression of PGHS-1 and PGHS-2 mRNA (P<0.001). These results indicate that early progesterone treatment does not control the expression of oxytocin-neurophysin mRNA in the ovine ovary but may be involved in the regulation of ovarian oxytocin receptor and PGHS expression. It is proposed, on the basis of these results, that progesterone may play a role in premature corpus luteum regression through an intra-ovarian mechanism involving the induction of ovarian oxytocin receptor mRNA expression.
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PMID:Effects of progesterone on expression of messenger RNA encoding oxytocin-neurophysin, oxytocin receptor and prostaglandin G/H synthase-1 and -2 during the early oestrous cycle in the ovine corpus luteum. 1110 Dec 80

Because criteria used for the prediction of preterm labor are poorly effective, many patients receive tocolytic therapy in excess during pregnancy. Beta-mimetic agonists are the reference tocolytic drugs in most countries. Their efficacy in prolonging pregnancy compared to a placebo is proven although no benefit in neonatal morbidity or mortality has been demonstrated. Beta-mimetics have many contraindications, and side-effects are frequent. Serious complications such as pulmonary edema and maternal deaths, though rare, have been reported. Recent research has focused on tocolytic drugs with similar efficacy to beta-mimetics but with less side effects. Calcium-channel-blockers and oxytocin antagonists have been compared with beta-agonists in randomized trials. Both have demonstrated similar efficacy in the prolongation of pregnancy for at least 48 hours. Contrary to beta-mimetics, very few interruptions of treatment have been observed with these treatments. Other tocolytic drugs such as cyclooxygenase inhibitors, although effective in prolonging pregnancy, have unacceptable fetal side effects. Progesterone, antispasmodic drugs and magnesium sulfate have been widely used but their efficacy has not been demonstrated. More recent treatments such as NO-donors and cyclooxygenase-II specific antagonists are not sufficiently evaluated. In conclusion, three main classes may be used as first line tocolytic therapy, beta-adrenergic agonists, calcium-channel-blockers, and oxytocin antagonists. The choice among these treatments may be based on contraindications to beta-mimetics, side-effects of the treatment, or even economic reasons.
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PMID:[Which tocolytic drugs in case of preterm labor?]. 1245 31

We used an animal model to study uterine leiomyoma in the context of pregnancy-associated changes in gene expression and to determine how they might modulate tumor growth. Spontaneous tumors and normal myometrium were collected from Eker rats and compared with myometrial samples from pregnant animals. A leiomyoma-derived cell line was also used to assess pregnancy-related changes in gene expression and to determine the impact of signaling by the oxytocin receptor. Eker rat leiomyomas expressed several pregnancy-related genes, including connexin 43, oxytocin receptor (OTR), and cyclooxygenase (COX)-1; however, the tumors did not express COX-2, which is expressed in the parturient myometrium. The leiomyoma-derived cell lines also expressed OTR, which responds to estrogen, binds to oxytocin, and exhibits a calcium flux when stimulated with oxytocin. The OTR signaling mediated by oxytocin inhibited estrogen-stimulated growth of leiomyoma cells. Leiomyoma cells expressed many genes of the parturient myometrium, including OTRs, but were deficient in COX-2 expression. Signaling via the OTR appears to inhibit estrogen-induced cell proliferation, suggesting that signaling by this receptor might help mediate the protective effect of pregnancy on this disease.
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PMID:Uterine leiomyomas express myometrial contractile-associated proteins involved in pregnancy-related hormone signaling. 1251 88

In ruminants, interferon produced by the trophectoderm (IFN-tau) is recognized as the embryonic signal responsible for maternal recognition of pregnancy. IFN-tau is believed to act by down-regulating estrogen receptors, thus preventing appearance of oxytocin receptors responsible for the release of prostaglandin F(2alpha) (PGF(2alpha)) by the endometrium. The present study was undertaken to determine in vitro the biological activities of different IFN-tau isoforms and document putative alternate luteotrophic mechanisms. Endometrial cells in primary cultures were treated with five different rIFN-tau isoforms: two ovine isoforms (ro-4 and ro-11) and three bovine isoforms (rb-1a, rb-2b and rb-3b). Their effect was quantified by measurement of PGE(2) and PGF(2alpha) production by ELISA and induction of cyclooxygenase (COX-2) by Western and Northern analysis and correlated with antiviral activity previously reported. The overall pattern of response to the IFNs tested suggests that low concentrations (<1 microg/ml) reduced the production of both PGs and higher concentrations (>1 microg/ml) stimulated preferentially PGE(2); however, exceptions were noted. Isoform rb-2b with high antiviral activity inhibited PG production in both cell types at all concentrations tested. IFNs rb-1a and ro-11 had similar antiviral activities, inhibiting PG at low concentrations and stimulating them at high concentrations. Isoform rb-3b stands out relative to the other IFNs tested because it induced a variable non-dose-dependent effect on PG production and low antiviral activity. An increase in COX-2 protein expression and messenger was correlated with increased PG production. The results showing two distinct responses to IFN-tau depending on its concentration and/or isoform and the absence of correlation with antiviral activity suggest that complex transduction mechanisms are involved.
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PMID:Influence of different isoforms of recombinant trophoblastic interferons on prostaglandin production in cultured bovine endometrial cells. 1260 58

In ruminants, the production of prostaglandins by the endometrium is critical for recognition of pregnancy. In the absence of an embryonic signal, luteolytic pulses of PGF(2 alpha) are released by the uterus. In contrast, the presence of a viable conceptus reduces the production of PGF(2 alpha) relative to PGE(2) and prevents luteolysis through the release of trophoblastic interferon (IFN-tau). Initially, it was thought that epithelial and stromal endometrial cells were specialized in the production of a single type of prostaglandin. However, purified cell populations of both types of cell can produce PGF(2 alpha) and PGE(2); therefore, selective production of PGF(2 alpha) and PGE(2) must be regulated within each type of cell. Two distinct prostaglandin synthases, cyclooxygenase 1 and cyclooxygenase 2, are involved in prostaglandin production and each may catalyse the production of a different prostaglandin. This possibility was investigated in cultured epithelial cells from bovine endometrium. Cells were treated with oxytocin or arachidonic acid, and expression of cyclooxygenase 1 and cyclooxygenase 2 proteins was monitored over time and correlated with prostaglandin accumulation. Cells were also treated with increasing doses of inhibitors of cyclooxygenase 1 or cyclooxygenase 2 (non-steroidal anti-inflammatory drugs; NSAIDs) with or without arachidonic acid or oxytocin: flurbiprofen (0-50 micromol l(-1)) was used as a non-selective inhibitor; valeryl salicylate (0-500 micromol l(-1)) was used as a cyclooxygenase 1 inhibitor and NS-398 (0-1 micromol l(-1)) was used as a cyclooxygenase 2 inhibitor. After stimulation with arachidonic acid or oxytocin, prostaglandin production and expression of cyclooxygenase 2 protein were increased. All inhibitors were able to block basal and stimulated prostaglandin production. These results indicate that in endometrium most, if not all, prostaglandin production is probably processed through cyclooxygenase 2.
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PMID:Evaluation of the contribution of cyclooxygenase 1 and cyclooxygenase 2 to the production of PGE2 and PGF2 alpha in epithelial cells from bovine endometrium. 1452 36

Prostaglandins, produced from membrane phospholipids by the action of phospholipase A2, cyclooxygenase, and specific prostaglandin synthases, are important regulators of ovulation, luteolysis, implantation, and parturition in reproductive tissues. Destruction of the corpus luteum at the end of the estrous cycle in nonpregnant animals is brought about by the pulsatile secretion of prostaglandin F(2alpha) (PGF(2alpha)) from the endometrium. It has been known for many years that progesterone, estradiol, and oxytocin are the hormones responsible for luteolysis. To achieve luteolysis, two independent processes have to be coordinated; the first is an increase in the prostaglandin synthetic capability of the endometrium and the second is an increase in oxytocin receptor number. Although progesterone and estradiol can modulate the expression of the enzymes involved in prostaglandin synthesis, the primary reason for the initiation of luteolysis is the increase in oxytocin receptor on the endometrial epithelial cells. Results of many in vivo studies have shown that progesterone and estradiol are required for luteolysis, but it is still not fully understood exactly how these steroid hormones act. The purpose of this article is to review the recent data related to how progesterone and estradiol could regulate (initiate and then turn off) the uterine pulsatile secretion of PGF(2alpha) observed at luteolysis.
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PMID:Steroid hormone modulation of prostaglandin secretion in the ruminant endometrium during the estrous cycle. 1497 58

Polyunsaturated fatty acids derived from the diet are incorporated into cell membranes where they act as precursors for prostaglandin (PG) synthesis. Linoleic acid (LA; 18:2 n-6) is a major constituent of plant oils and its consumption in Westernized populations is increasing. This study investigated the influence of LA on PG production by the uterus and placenta. Pregnant ewes were fed a control or an LA-enriched diet. Oxytocin (OT) was injected on day 45 (early) or day 133 (late) of gestation to measure the release of 13,14-dihydro-15-keto PGF(2alpha) (PGFM). Ewes were killed on day 46 or day 138 for collection of uterine intercaruncular endometrium and fetal allantochorion. Basal and stimulated PG release from explant cultures was assessed before and after in vitro treatment with OT, lipopolysaccharide (LPS), dexamethasone (DEX) or calcium ionophore (CaI). Expression of cyclooxygenase (COX)-1 and COX-2 was determined by Western blot in endometrium of late-gestation ewes. Circulating PGFM levels in vivo did not differ according to diet but there were highly significant differences in the release of PGs in vitro. Basal production of PGF(2alpha)and PGE(2) by the endometrium and of PGE(2) by the allantochorion were all higher in tissues from LA-supplemented ewes. Endometrial tissues produced more PG following OT and CaI treatment, whereas DEX inhibited production of both PGs at both stages of gestation. In allantochorion collected at day 46 LPS did not significantly alter PGE(2) release and DEX increased output, whereas at day 138 LPS was stimulatory but DEX was inhibitory. These data show that a high-LA diet can significantly increase the ability of both endometrium and placental tissues to produce PGs in vitro. This effect of diet may only become apparent after a sustained period of PG release, so was not seen following the brief pulse caused by OT treatment in vivo. As COX protein levels were unaltered, the main influence was likely to be via conversion of LA to arachidonic acid, providing an increased supply of precursor. These results support previous studies which suggest that alterations in dietary polyunsaturated fatty acids may influence the time of labour.
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PMID:The effect of a diet supplemented with the n-6 polyunsaturated fatty acid linoleic acid on prostaglandin production in early- and late-pregnant ewes. 1564 93

Nitric oxide (NO) affects reproductive processes both at the level of the brain and reproductive tract and this review is focused on its role as an essential regulator of the hypothalamic control of reproduction. The data gathered indicate that glutamate stimulates noradrenergic neurons which subsequently activate NO-ergic cells via alpha1-adrenergic receptors. The released NO diffuses into luteinizing hormone-releasing hormone (LHRH) terminals where it triggers LHRH secretion by activation of guanylyl cyclase and cyclooxygenase. The NO released by estrogen-stimulated NO-ergic ventromedial neurons plays a crucial role in the regulation of sexual behavior. Furthermore, an increased expression of inducible nitric oxide synthase in the LHRH and oxytocin neurons underlies the destructive action of NO on the aging of the hypothalamic neuroendocrine pathways. Within the hypothalamo-hypophyseal system, NO exerts an inhibitory effect in the control of oxytocin secretion. This action seems to employ an indirect mechanism by which NO may modulate the release of GABA. This review provides an overview of the role of NO in hypothalamic control of LHRH and oxytocin release, aging of the LHRH and oxytocin neurons and sexual behavior.
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PMID:The role of nitric oxide in the hypothalamic control of LHRH and oxytocin release, sexual behavior and aging of the LHRH and oxytocin neurons. 1658 85

Nitric oxide (NO) was initially described as a mediator of endothelial relaxation, and now its participation is recognized in numerous physiological and pathological processes. It was demonstrated that lipopolysaccharide-stimulated corticotropin-releasing factor release involves NO production. Furthermore, it has been shown that interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, IL-6, and IL-2 can stimulate adrenocorticotropic hormone release from anterior pituitary via NO. Also, we found that NO released from hypothalamic NOergic neurons in response to norepinephrine diffuses to luteinizing hormone-releasing hormone (LHRH) neurons that activate cyclooxygenase and guanylate cyclase. This activation results in an increase in prostaglandin E2 and cyclic guanosine monophosphate, respectively, which leads to the exocytosis of LHRH granules. During pathological conditions, such as manganese intoxication, NO production is increased, leading to an increase in LHRH secretion that can advance puberty. In another study we demonstrated that NO reduces oxytocin as well as vasopressin secretion from the posterior pituitary, suggesting it has a modulatory role during dehydration. An increase in NO synthase (NOS) activity and protein in the hippocampus and cerebellum was found in offspring of rats that were subjected to prenatal stress, and this was correlated with behavioral changes in adults. Also NO participates in signal transduction pathways in peripheral tissue in physiological processes, such as in corticosterone release from the adrenal gland. Pathological conditions, such as tumors of the head and neck, that are treated with radiation are followed by xerostomy. In a rat model, radiation diminished NOS activity in the submandibulary gland, and this was followed by inhibition in salivary secretion. In summary, this review describes the wide participation of NO in the cross-talk between neuroendocrine and neuroimmune systems in physiological and pathological processes.
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PMID:Nitric oxide at the crossroad of immunoneuroendocrine interactions. 1923 26

Scutellariae Radix is one of the well-known tocolytic Chinese herbs. Oroxylin A is isolated from the root of Scutellaria baicalensis. The main syndrome of preterm birth is caused by uterus contractions from excitatory factors. Administration of tocolytic agents is a strategy to prevent the occurrence of preterm births. The aim of this study was to investigate the effects of oroxylin A on contractions of uterine strips isolated from non-pregnant female Wistar rats (250-350 g). Contractions of the uterus were induced with acetylcholine (Ach) (1 microM), PGF2alpha (0.1 microM), oxytocin (10-3 U/ml), KCl (56.3 mM), tetraethylammonium (TEA; 1 and 10 mM), 4-aminopyridine (4-AP; 5 mM), glipizide (30 microM), a nitric oxide synthase (NOS) inhibitor (LNNA; 10-3M), a beta-receptor blocker (propranolol; 10 microM), and a cyclooxygenase inhibitor (indomethacin; 60 microM). The inhibitory effects of the amplitude and frequency of spontaneous contractions by oroxylin A were antagonized with Ach (IC50 22.85 microM), PGF2alpha (IC5027.28 microM), oxytocin (IC50 12.34 microM), TEA; 1 and 10 mM (IC50 52.73 and 76.43 microM), 4-AP (IC50 67.16 microM), and glipizide (IC5027.53 microM), but oroxylin A was not influenced by Ca2+-free medium, LNNA, propranolol, or indomethacin. Otherwise, oroxylin A-mediated relaxation of the rat uterus might occur through opening of uterine calcium-dependent potassium channels or adenosine triphosphate potassium channel activation. This suggests that oroxylin A is the tocolytic principle constituent of Scutellariae Radix, and oroxylin A may provide a lead compound for new tocolytic drug development in the future.
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PMID:In vitro study of the tocolytic effect of oroxylin A from Scutellaria baicalensis root. 1927 27


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