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

A prospective study was carried out at a tertiary care hospital on 100 pregnant women admitted for induction of labour to compare the effect of misoprostol and dinoprostone on the induction of labour. The patients were divided randomly into two groups of 50 each. Group I received 25 microg misoprostol intravaginally every 3 h (maximum dose 200 microg), and Group II received 0.5 mg PGE(2) gel (dinoprostonev) intracervically every 6 h (maximum three doses in 24 h) until good uterine contractions started. The primary outcome measure was vaginal delivery occurring within 24 h of administration of the first dose of either study drug (successful induction). Statistical analysis were conducted using chi(2) test, Fisher exact test, Student's t-test and relative risk (RR) with 95% confidence interval (CI). In the misoprostol group, more patients achieved successful inductions as compared with the dinoprostone group, 80% vs. 62% (P = 0.0473, RR 1.63, 95% CI 0.95-2.81). The mean induction to delivery interval (IDI) was shorter in the misoprostol group, 13.30+/-8.74 (3-40.15) hours, as compared with the dinoprostone group, 18.53+/-11.33 (2-48.07) hours (P = 0.011). Misoprostol was associated with significantly less oxytocin use (18% vs. 50%) as compared with dinoprostone (P = 0.001 RR 0.36, 95% CI 0.19-0.69). In conclusion, although both misoprostol and dinoprostone appear to be effective agents for labour induction, misoprostol is cheaper, stable at room temperature, has shorter IDI and requires less oxytocin. These results make misoprostol superior to dinoprostone for induction of labour especially in developing and tropical countries.
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PMID:Induction of labour with intravaginal misoprostol and prostaglandin E2 gel: a comparative study. 1732 81

It has been earlier proposed that oxytocin could play a facilitatory role in the preovulatory LH surge in both rats and humans. We here provide evidence that oxytocin also facilitates sexual maturation in female rats. The administration of an oxytocin antagonist for 6 d to immature female rats decreased GnRH pulse frequency ex vivo and delayed the age at vaginal opening and first estrus. The in vitro reduction in GnRH pulse frequency required chronic blockade of oxytocin receptors, because it was not acutely observed after a single injection of the antagonist. Hypothalamic explants exposed to the antagonist in vitro showed a reduced GnRH pulse frequency and failed to respond to oxytocin with GnRH release. Prostaglandin E(2) (PGE(2)) mimicked the stimulatory effect of oxytocin on GnRH pulse frequency, and inhibition of PG synthesis blocked the effect of oxytocin, suggesting that oxytocin accelerates pulsatile GnRH release via PGE(2). The source of PGE(2) appears to be astrocytes, because oxytocin stimulates PGE(2) release from cultured hypothalamic astrocytes. Moreover, astrocytes express oxytocin receptors, whereas GnRH neurons do not. These results suggest that oxytocin facilitates female sexual development and that this effect is mediated by a mechanism involving glial production of PGE(2).
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PMID:Oxytocin facilitates female sexual maturation through a glia-to-neuron signaling pathway. 1803 81

Several factors participate in regulation of growth and development as well as angiogenesis of the uterus during pregnancy, and hence little is known about the role of hormonal regulation of vascular endothelial growth factor (VEGF)-receptor system expression. This study has examined the effect of insulin-like growth factor-I (IGF-I), relaxin (RLX), oxytocin (OT) and prostaglandin (PG) E(2), on VEGF secretion and VEGF-receptor system mRNA expression in the porcine endometrial stromal cells. IGF-I and RLX were identified as the most effective inducers of VEGF secretion and mRNA expression. Although PGE(2) stimulated VEGF secretion and VEGF164 mRNA expression, OT inhibited both secretion and mRNA expression of VEGF. When tested for VEGF receptors (R), all factors failed to affect their mRNA expression. Media conditioned by stromal cells collected after IGF-I and RLX treatment significantly increased endothelial cell proliferation and this effect was blocked by soluble VEGFR-1. These data suggest that during early pregnancy IGF-I, RLX and PGE(2) can affect VEGF expression in the endometrium and therefore may support uterine and embryo development, implantation and pregnancy.
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PMID:Assessment of VEGF-receptor system expression in the porcine endometrial stromal cells in response to insulin-like growth factor-I, relaxin, oxytocin and prostaglandin E2. 1856 87

The aim of our in vitro experiments was to examine the role of transcription factor p53 in controlling the basic functions of ovarian cells and their response to hormonal treatments. Porcine ovarian granulosa cells, transfected and non-transfected with a gene construct encoding p53, were cultured with ghrelin and FSH (all at concentrations of 0, 1, 10, or 100 ng/ml). Accumulation of p53, of apoptosis-related (MAP3K5) and proliferation-related (cyclin B1) substances was evaluated by immunocytochemistry. The secretion of progesterone (P(4)), oxytocin (OT), prostaglandin F (PGF), and E (PGE) was measured by RIA. Transfection with the p53 gene construct promoted accumulation of this transcription factor within cells. It also stimulated the expression of a marker of apoptosis (MAP3K5). Over-expression of p53 resulted in reduced accumulation of a marker of proliferation (cyclin B1), P(4), and PGF secretion and increased OT and PGE secretion. Ghrelin, when added alone, did not affect p53 or P(4), but reduced MAP3K5 and increased PGF and PGE secretion. Over-expression of p53 reversed the effect of ghrelin on OT, caused it to be inhibitory to P(4) secretion, but did not modify its action on MAP3K5, PGF, or PGE. FSH promoted the accumulation of p53, MAP3K5, and cyclin B1; these effects were unaffected by p53 transfection. These multiple effects of the p53 gene construct on luteinizing granulosa cells, cultured with and without hormones 1) demonstrate the effects of ghrelin and FSH on porcine ovarian cell apoptosis and secretory activity, 2) confirm the involvement of p53 in promoting apoptosis and inhibiting P(4) secretion in these cells, 3) provide the first evidence that p53 suppress proliferation of ovarian cells, 4) provide the first evidence that p53 is involved in the control of ovarian peptide hormone (OT) and prostaglandin (PGF and PGE) secretion, and 5) suggest that p53 can modulate, but probably not mediate, the effects of ghrelin and FSH on the ovary.
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PMID:Transcription factor p53 can regulate proliferation, apoptosis and secretory activity of luteinizing porcine ovarian granulosa cell cultured with and without ghrelin and FSH. 1870 74

Interferon-tau (IFNtau) is the embryonic signal responsible for pregnancy recognition in ruminants. The primary action of IFNtau is believed to be mediated through inhibition of prostaglandin F(2alpha) (PGF(2alpha)) released from the endometrial epithelial cells in response to oxytocin (OT). Our working hypothesis was that the antiluteolytic effect of IFNtau also involved modulation of PG production downstream of OT receptor (OTR) and/or cyclooxygenase 2 (COX2). There is currently no OT-sensitive endometrial cell line to study the molecular mechanisms underlying our hypotheses. Therefore, we established an immortalized bovine endometrial epithelial cell line (bEEL) exhibiting OT response. These cells were cytokeratin positive, expressed steroid receptors, and exhibited preferential accumulation of PGF(2alpha) over PGE(2). The bEEL cells were highly sensitive to OT, showing time- and concentration-dependent increase in COX2 transcript and protein and PGF(2alpha) accumulation. Interestingly, IFNtau (20 ng/ml) significantly reduced OT-induced PGF(2alpha) accumulation, but surprisingly, the effect was not mediated through down-regulation of either OTR or COX2. Rather, IFNtau up-regulated COX2 in a time- and concentration-dependent manner while decreasing OT-induced PG accumulation. This suggests that COX2 is not a primary target for the antiluteolytic effect of IFNtau. Because IFNtau reduced OT-stimulated PGF(2alpha) accumulation within 3 h, the mechanism likely involves a direct interference at the level of the OT signaling or transcription in addition to the down-regulation of OTR observed in vivo. In summary, bEEL cells offer a unique in vitro model for investigating the cellular and molecular mechanisms underlying OT and IFNtau response in relation with luteolysis and recognition of pregnancy in the bovine.
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PMID:Oxytocin receptor down-regulation is not necessary for reducing oxytocin-induced prostaglandin F(2alpha) accumulation by interferon-tau in a bovine endometrial epithelial cell line. 1883

Escherichia coli infection of the endometrium causes uterine disease after parturition and is associated with prolonged luteal phases of the ovarian cycle in cattle. Termination of the luteal phase is initiated by prostaglandin F(2alpha) (PGF) from oxytocin-stimulated endometrial epithelial cells. Compared with normal animals, the peripheral plasma of animals with E. coli infection of the endometrium had higher concentrations of lipopolysaccharide (LPS) and prostaglandin E(2) (PGE) but not PGF. Endometrial explants accumulated predominantly PGE in the culture medium in response to LPS, and this effect was not reversed by oxytocin. Endometrial cells expressed the Toll-like receptor 4/CD14/MD-2 receptor complex necessary to detect LPS. Epithelial and stromal cells treated with LPS had higher steady-state media concentrations of PGE rather than PGF. Arachadonic acid is liberated from cell membranes by phospholipase 2 (PLA2) enzymes and converted to prostaglandins by synthase enzymes. Treatment of epithelial and stromal cells with LPS did not change the levels of PGE or PGF synthase enzymes. However, LPS stimulated increased levels of PLA2 group VI but not PLA2 group IV C immunoreactive protein in epithelial cells. Endometrial cells expressed the E prostanoid 2 and E prostanoid 4 receptors necessary to respond to PGE, which regulates inflammation as well as being luteotropic. In conclusion, LPS detection by endometrial cells stimulated the accumulation of PGE rather than PGF, providing a mechanism to explain prolonged luteal phases in animals with uterine disease, and this PGE may also be important for regulating inflammatory responses in the endometrium.
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PMID:Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F2alpha to prostaglandin E2 in bovine endometrium. 1905 17

In the pig, the periimplantation period is critical for successful establishment of pregnancy. We studied the influence of embryos on oxytocin (OT) and progesterone (P(4)) regulated endometrial and myometrial secretion of 1) luteotrophic prostaglandin E(2) (PGE(2)) and 2) luteolytic prostaglandin F(2alpha) and its metabolite (PGFM) on days 12-14 of pregnancy in pigs. We used unilaterally pregnant pigs created by a surgical procedure in which one uterine horn remained intact and the second horn was cut transversely so that part of the horn was detached from the uterine body. The animals were divided into two groups, inseminated gilts (days 12-14 of pregnancy, n=6) and uninseminated cyclic gilts, which were used as controls (days 12-14 of estrous cycle, n=5). Embryos developed only in the patent part of the uterus and not in the occluded horn. The abundance of OTR mRNA was increased in the endometrium and decreased in the myometrium of the gravid uterine horn in the pregnant pigs compared with the non-gravid uterine horn or either uterine horn in the cyclic pigs, indicative of a local effect of the conceptus. The presence of embryos in the uterine horn during the periimplantation period determines endometrial metabolism of PGF(2alpha) and the local response of the endometrium to OT and P(4). OT stimulates PGF(2alpha) secretion and PGFM accumulation in endometrial cultures only from the non-gravid uterine horn and controls PGE(2) secretion from the endometrium and myometrium in the pregnant gilts. The results indicate a more systemic affect of pregnancy on the uterine response to OT and a possibly the local effect of the conceptus in promoting progesterone's inhibition of OT-stimulated PGE(2) secretion and uterine metabolism of PGF(2alpha).
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PMID:Local and systemic effects of embryos on uterine tissues during early pregnancy in pigs. 1929 62

Oxytocin (OXT) is a potent stimulator of prostaglandin E(2) (PGE(2)) synthesis by rabbit amnion cells obtained near the end of pregnancy. Coincident with a marked increase in sensitivity of PGE(2) synthesis to OXT, the concentration of OXT receptors (OXTRs) is abruptly upregulated about 200-fold at term. This increase can be mimicked in preterm amnion cells in primary culture by the synergistic action of agents that increase cAMP synthesis and by glucocorticoids. To elucidate the mechanism of cAMP action, we cloned the rabbit OXTR gene and isolated a 200-base pair (bp) forskolin-responsive region about 4.7 kilobase upstream from the transcriptional start site using transient transfection assays. This region corresponds to a DNase I-hypersensitive site that appears in amnion tissue only near the end of pregnancy, when OXTRs are upregulated. The effects of forskolin were mediated in part by cAMP response element binding protein (CREB), as coexpression of reporter constructs with dominant negative CREB inhibited reporter expression. In addition, CREB was cross-linked to sites in the 200-bp region only in chromatin isolated from cells near the end of pregnancy, as demonstrated by chromatin immunoprecipitation (ChIP). Because the transient transfection results are consistent with work using tissue extracts (DNase I hypersensitivity and ChIP), we conclude that cAMP, acting through a specific upstream CREB binding site, is critical for the physiological upregulation of OXTRs in the amnion at the end of gestation.
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PMID:Characterization of the cyclic adenosine monophosphate target site in the oxytocin receptor gene in rabbit amnion. 1943 25

The antiprogestin mifepristone (RU 486) is used for termination of pregnancy, as RU 486 blocks the quiescent action of progesterone, increases uterine contractility, sensitizes the myometrium to prostaglandins, and elicits cervical ripening. Since RU 486 represents a class of compound that is structurally related to steroid hormones, some of which possess a nongenomic uterine relaxing effect, we investigated the potential nongenomic relaxing action of RU 486 on the human pregnant myometrium. Myometrial tissues were obtained from pregnant women undergoing elective cesarean section at term and were isometrically recorded. RU 486 caused relaxation on spontaneous contractility and high potassium-induced contractions with lower relaxing efficacy than progesterone. The progesterone receptor-blocking activity of RU 486 did not antagonize the uterine relaxation of progesterone. Moreover, contractions induced by oxytocin or different prostaglandins (PGF(2alpha), PGE(2), and a prostaglandin analogue, misoprostol) were inhibited rather than increased by RU 486. RU 486 induced a rapid and reversible relaxing effect, which was unaffected by inhibitors of protein synthesis and transcription, implying that RU 486 acts through a nongenomic mechanism. This study reveals that RU 486: (i) reduced high potassium-induced contraction and prevented calcium-induced contraction in depolarized tissue; and (ii) relaxed the oxytocin- and prostaglandin-induced contractions, indicating a blockade of voltage- and receptor-operated calcium channels by RU 486. These data show that this antiprogestin may induce a rapid nongenomic antiuterotonic effect prior to its antiprogesterone action.
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PMID:Nongenomic uterine relaxing effect of RU 486 (mifepristone) prior to its antiprogesterone activity in the human pregnancy. 1946 6

Lysophosphatidic acid (LPA) has been shown to be a potent modulator of prostaglandin (PG) secretion during the luteal phase of the estrous cycle in the bovine endometrium in vivo. The aims of the present study were to determine the cell types of the bovine endometrium (epithelial or stromal cells) responsible for the secretion of PGs in response to LPA, the cellular, receptor, intracellular, and enzymatic mechanisms of LPA action. Cultured bovine epithelial and stromal cells were exposed to LPA (10(-5)-10(-9) M), tumor necrosis factor alpha (TNFalpha; 10 ng/mL) or oxytocin (OT; 10(-7) M) for 24 h. LPA treatment resulted in a dose-dependent increase of PGE(2) production in stromal cells, but not in epithelial cells. LPA did not influence PGF(2alpha) production in stromal or epithelial cells. To examine which type of LPA G-protein-coupled receptor (LP-GPCR; LPA1, LPA2, or LPA3) is responsible for LPA action, stromal cells were preincubated with three selected blockers of LPA receptors: NAEPA, DGPP, and Ki16425 for 0.5 h, and then stimulated with LPA. Only Ki16425 inhibited the stimulatory effect of LPA on PGE(2) production and cell proliferation in the stromal cells. LPA-induced intracellular calcium ion mobilization was also inhibited only by Ki16425. Finally, we examined whether LPA-induced PGE(2) synthesis in stromal cells is via the influence on mRNA expression for the enzymes responsible for PGE(2) synthesis-PGE(2) synthase (PGES) and PG-endoperoxide synthase 2 (PTGS2). We demonstrated that the stimulatory effect of LPA on PGE(2) production in stromal cells is via the stimulation of PTGS2 and PGES mRNA expression in the cells. The overall results indicate that LPA stimulates PGE(2) production, cell viability, and intracellular calcium ion mobilization in cultured stromal endometrial cells via Ki16425-sensitive LPA1 receptors. Moreover, LPA exerts a stimulatory effect on PGE(2) production in stromal cells via the induction of PTGS2 and PGES mRNA expression.
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PMID:Lysophosphatidic acid stimulates prostaglandin E2 production in cultured stromal endometrial cells through LPA1 receptor. 1949 66


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