UNIPROT:P01178 - FACTA Search

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

Maintenance of corpus luteum (CL) function is essential for establishment of pregnancy in mammals. Estrogens from pig conceptuses (embryo and associated membranes) initiate events that, with prolactin, redirect secretion of the uterine luteolytic hormone prostaglandin F2 alpha (PGF) from an endocrine (to uterine veins) to an exocrine (to uterine lumen) direction to prevent luteolysis. Ovine conceptuses secrete ovine trophoblast protein-1 (oTP-1), which exhibits high amino acid sequence relatedness with alpha II interferons (IFN alpha II) and inhibits synthesis of endometrial receptors for oxytocin and uterine production of luteolytic pulses of PGF. Estrogens and oTP-1 are local antiluteolytic signals to endometrium, whereas human chorionic gonadotrophin (hCG) appears to have a direct luteotrophic effect on CL. A progestational endometrium secretes proteins that serve as growth factors, transport proteins, regulatory proteins and enzymes, as well as transporting nutrients into the uterine lumen to support conceptus development.
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PMID:Comparative aspects of conceptus signals for maternal recognition of pregnancy. 206 81

The neuroendocrine antidiuretic hormone arginine vasopressin (AVP) was capable of replacing the interleukin 2 (IL 2) requirement for gamma-interferon (IFN gamma) production by Lyt-2+ cells from C57BL/6 mouse spleen cells. The AVP replacement did not stimulate DNA synthesis in the target lymphocytes. This suggested that AVP was capable of replacing an IL 2 function that did not involve stimulation of cellular proliferation or DNA synthesis. This was confirmed by the demonstration that mitomycin C inhibition of IFN gamma production was reversed by IL 2 or AVP without concomitant reversal of blockage of DNA synthesis. Oxytocin, which is structurally related to AVP, was also capable of replacing IL 2 requirement for IFN gamma production, whereas insulin was ineffective. The data show that the neuroendocrine hormones AVP and oxytocin are capable of lymphokine-like activity. This activity may involve the induction of a second messenger such as cyclic GMP.
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PMID:Vasopressin replacement of interleukin 2 requirement in gamma interferon production: lymphokine activity of a neuroendocrine hormone. 618 8

Luteolysis in sheep is associated with uterine secretion of pulses of prostaglandin F2 alpha (PGF2 alpha) due to the action of luteal oxytocin on endometrial oxytocin receptors. For pregnancy to become established inhibition of oxytocin receptors is important as an antiluteolytic mechanism. The maternal recognition of pregnancy in cattle and sheep involves production, by the trophoblast, of a type 1 interferon (IFN-tau) that suppresses uterine development of oxytocin receptors and the generation of luteolytic episodes of PGF2 alpha. The action of IFN-tau in surgically prepared unilaterally pregnant ewes was investigated. Finn-Dorset ewes were anaesthetized on day 6 or 7 of the oestrous cycle and one uterine horn was surgically isolated at the uterine bifurcation from the body of the uterus. Ewes were mated at the subsequent oestrus either by a fertile or by a vasectomized ram and killed on day 13 or 16 after mating. On day 16, in the non-pregnant ewes, there was no measurable uterine IFN-tau but there were high concentrations of oxytocin receptors in both horns. In the pregnant ewes on day 16 after mating, the oxytocin receptor concentration was 45 +/- 11 fmol mg-1 protein in the pregnant horn and 585 +/- 131 fmol mg-1 in the non-pregnant horn. Antiviral activity was 5.8 x 10(7) +/- 5.2 x 10(7) U ml-1 in the pregnant horn and 2.9 x 10(3) +/- 1.2 x 10(3) U ml-1 in the non-pregnant horn. Thus, 16 days after mating, the pregnant horn exhibited high antiviral activity but oxytocin receptors were suppressed, while in the same endocrine environment (characteristic of pregnancy) there were low IFN-tau and high oxytocin receptor concentrations in the isolated horn equivalent to those expected at the onset of luteolysis. In situ hybridization to ovine mRNA encoding the oxytocin receptor and autoradiographic studies using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin both showed that the large amount of oxytocin receptor message and binding sites in the endometrium of the isolated horn were localized in the luminal epithelium. Immunocytochemical studies showed that there was a suppression of oestradiol receptors in the pregnant horn but high concentrations equivalent to those at oestrus were present in the isolated horn. The content of progesterone receptors was low in the stromal tissue only in both horns, a pattern of localization similar to that seen in the late luteal phase and in early pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Local action of trophoblast interferons in suppression of the development of oxytocin and oestradiol receptors in ovine endometrium. 749 Jul 9

Enhanced secretion of PGF2 alpha from endometrial explants in vitro in response to oxytocin is associated with augmented activities of phospholipase A2, phospholipase C and prostaglandin endoperoxide H synthase (PGS). In early pregnancy, maintenance of the corpus luteum is associated with an absence of pulsatile PGF2 alpha secretion; an increase in endometrial inhibitors of phospholipase A2 and PGS contribute to the antiluteolytic alterations of PGF2 alpha secretion. Linoleic acid is a competitive inhibitor of arachidonic acid metabolism by PGS, and microsomal concentrations of free linoleic acid are increased in the endometrium of pregnant cattle. The trophoblast produces large quantities of interferon tau (IFN-tau). Inhibition of increases in endometrial oestradiol receptor mRNA and protein are associated with intrauterine administration of recombinant (r) ovine (o) IFN-tau in sheep. Intrauterine injections of ovine (b) IFN-tau in cattle (days 14-17) altered endometrial function so that secretion of PGF2 alpha from cultured endometrial epithelial cells was reduced. Antiluteolytic effects were not expressed in 20% of cows receiving IFN-tau or rbIFN-alpha I1 indicating that an inadequate endometrial responsiveness may contribute to embryo mortality. IFN-tau may activate a signal transduction system similar to that induced by other type I IFNs; activation of an intracellular tyrosine kinase ultimately leads to activation of an IFN-stimulated response element to induce gene transcription. Biological responses associated with pregnancy and IFN-tau treatment are integrated into a multifactorial antiluteolytic model. Strategies to enhance embryo survival could include supplementation with rIFN-tau and alterations in endometrial responsiveness to this cytokine through dietary manipulation of lipid metabolism.
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PMID:Maternal recognition of pregnancy. 762 10

The effects of bovine interferon tau (IFN tau) and oxytocin on secretion of the prostaglandins PGF2 alpha and PGE2 by epithelial and stromal cells in the endometrium were assessed in two experiments. Endometrial tissues were collected from cyclic cows at Day 15 after oestrus for subsequent isolation of epithelial cells (4 cows) and stromal cells (4 cows). In both experiments, confluent cells were treated with 0, 2, 10 or 50 ng mL-1 natural bovine IFN tau (nbIFN tau) or 0, 0.4, 2, 10, 50 and 250 ng mL-1 recombinant bIFN tau (rbIFN tau). Culture medium was sampled at 24 h. Oxytocin (2.0 x 10(-7) M) or placebo was then added to wells and the medium was sampled 30 and 90 min later. Epithelial cells secreted more PGF2 alpha than stromal cells whereas stromal cells predominantly secreted PGE2. Oxytocin stimulated secretion of PGF2 alpha and PGE2 (P < 0.01) from epithelial cells, but both basal secretion and oxytocin-induced secretion of PGF2 alpha and PGE2 decreased with increasing dose of either nbIFN tau or rbIFN tau (P < 0.01). At comparable doses, rbIFN tau inhibited PGF2 alpha and PGE2 secretion more strongly than did nbIFN tau (either in the absence or the presence of oxytocin). The minimal effective dose of rbIFN tau was 0.4 ng mL-1 and 50% inhibition was obtained with 1 ng mL-1 (0.043 nM). Neither nbIFN tau nor rbIFN tau nor oxytocin altered PGF2 alpha or PGE2 secretion by stromal cells. The results indicate differential prostaglandin responses by the two major endometrial cell types (epithelium and stroma) to regulatory agents such as bIFN tau and oxytocin in cattle. Suppression of prostaglandin secretion by bIFN tau in epithelial cells of endometrial tissue is supportive of an antiluteolytic effect of bIFN tau.
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PMID:Natural and recombinant bovine interferon tau regulate basal and oxytocin-induced secretion of prostaglandins F2 alpha and E2 by epithelial cells and stromal cells in the endometrium. 799 88

The sheep endometrial oxytocin receptor plays a central role in determining the time at which luteolysis occurs during the oestrous cycle, and in the events leading to the establishment of pregnancy (the maternal recognition of pregnancy). Expression of the receptor in the uterus is controlled by ovarian steroid hormones, and by trophoblast interferon (IFN-tau). We report here studies on the second messengers involved in the effect of IFN-tau, and on the structure and expression of the oxytocin receptor. The receptor is expressed in ovine endometrial explants during culture, when the explants are taken during the luteal phase of the cycle; this process is partially blocked by inhibitors of protein kinase C, or by down-regulation of protein kinase C. Therefore it is suggested that protein kinase C, rather than tyrosine kinases, is involved in the effect of IFN-tau on oxytocin receptor expression. Northern blotting shows that in common with uterine oxytocin receptor mRNA in other species, the message is heterogeneous. cDNA sequencing indicates the sheep uterine oxytocin receptor is at least 2 amino acids longer than those of other species, and expression of the receptor in Cos-7 cells induces oxytocin responsiveness in terms of phosphoinositide turnover.
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PMID:The sheep endometrial oxytocin receptor. 871 78

This study determined the effects of intrauterine injections of recombinant ovine interferon-tau; (roIFN-tau; 2 x 10(7) antiviral units/day) or control proteins (6 mg/day) from day 11 to day 14 post-oestrus = day 0) on endometrial expression of receptors fro oestrogen, progesterone and oxytocin in cyclic ewes. Plasma concentrations of progesterone were greater on day 15 in ewes receiving roIFN-tau compared with control proteins (P < 0.02, treatment x day). Ewes injected with roIFN-tau had lower endometrial levels or oestrogen receptor mRNA (P > 0.10) and protein (P < 0.01) on day 15 compared with ewes receiving control proteins. In situ hybridization analysis indicated that oestrogen receptor mRNA was more abundant in the luminal and glandular epithelium of control ewes compared with roIFN-tau-treated ewes. Immunoreactive oestrogen receptor was also present in the luminal and glandular epithelium of control, but not roIFN-tau-treated ewes. Endometrial levels of progesterone receptor mRNA and protein were not different (P > 0.10) between control and roIFN-tau-treated ewes. In situ hybridization analyses indicated that progesterone receptor mRNA abundance was low in endometrial epithelium and stroma of both control and roIFN-tau-injected ewes. Immunoreactive progesterone receptors were present in the endometrial stroma and epithelium of control ewes, but confined to the stroma of roIFN-tau-treated ewes. Oxytocin receptor density was lower (P < 0.01) in the endometrium of ewes injected with roIFN-tau than control proteins; however, oxytocin receptor affinity was not affected (P > 0.10) by treatment. Concentrations of 13,14-dihydro-15-ketoprostaglandin F2a (PGFM) were not increased by exogenous oxytocin administration in control and roIFN-tau-treated ewes on days 10 or 12 post-oestrus. However, on day 14, control ewes responded to oxytocin with increased plasma concentrations of PGFM, whereas ewes receiving roIFN-tau remained unresponsive to oxytocin. These results indicate that the an tiluteolytic effects of IFN-tau are to prevent increases in endometrial oestrogen receptor MRNA and protein and oxytocin receptor density which abrogates uterine release of prostaglandin F2a during maternal recognition of pregnancy. IFN-tau may inhibit the synthesis of oestrogen receptor mRNA by a transcriptional or post-transcriptional regulatory mechanism to suppress oxytocin receptor formation during early pregnancy in ewes.
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PMID:Intrauterine injection of ovine interferon-tau alters oestrogen receptor and oxytocin receptor expression in the endometrium of cyclic ewes. 880 Jun 45

The effects of recombinant ovine interferon-tau (IFN-tau) and progesterone on oestrogen-stimulated expression of endometrial receptors for oestrogen (ER), progesterone (PR) and oxytocin (OTR) were determined in ovariectomized ewes. Cyclic ewes (n = 16) were ovariectomized and fitted with uterine catheters on Day 4 of the oestrous cycle (Day O, oestrous) and assigned randomly in 2 x 2-factorial arrangement to receive daily intrauterine injections of either recombinant ovine IFN-tau (roIFN-tau; 2 x 10(7) anti-viral units) or control proteins from Day 11 to Day 15 and 50 mg progesterone from either Day 4 to Day 10 (E-P) or Day 4 to Day 15 (E+P). All ewes received 50 micrograms oestradiol-17 beta on Days 13, 14 and 15 and were hysterectomized on Day 16. In control ewes, endometrial ER mRNA, PR protein and OTR density were greater in E-P- than E+P- treated ewes. In E-P ewes, roIFN-tau decreased oestrogen-stimulated increases in ER and OTR, but not PR expression compared with control ewes. In E+P ewes, endometrial ER mRNA and protein, PR mRNA and protein, and OTR levels were lower in roIFN-tau-treated ewes than control ewes. Immunoreactive ER and PR were absent in the endometrial luminal and superficial glandular epithelium of roIFN-tau compared with control ewes, but were present in the deep glandular epithelium and stroma regardless of steroid or protein treatment. These results indicate that progesterone affects oestrogen-induced increases in endometrial ER, PR and OTR expression in the PR+ deep glandular epithelium and stroma, whereas IFN-tau suppresses oestrogen-induced increases ER, PR and OTR expression in the PR- luminal and superficial glandular epithelium. These combined actions of IFN-tau and progesterone to suppress oestrogen-induced increases in endometrial OTR formation would prevent pulsatile production of luteolytic prostaglandin F2 alpha by the endometrium during early pregnancy.
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PMID:Effects of interferon-tau and progesterone on oestrogen-stimulated expression of receptors for oestrogen, progesterone and oxytocin in the endometrium of ovariectomized ewes. 887 43

At the time of recognition of pregnancy, the bovine conceptus (embryo and associated membranes) must produce a signal that will prevent luteolysis otherwise induced by pulsatile release of prostaglandin (PG) F2alpha from the uterus in response to oxytocin (OT). In ruminants, trophoblastic interferon tau (IFN-tau) released by the conceptus appears to be the most likely candidate to trigger the establishment of pregnancy. We have compared the effect of recombinant (r) ovine (o) and bovine (b) IFN-tau on PG production, using a fully characterized model of cultured endometrial cells. In uterine epithelial cells, the production of PGF2alpha was stimulated 7.1-fold (p < 0.0001) and that of PGE2 89.0-fold (p < 0.0001) by rbIFN-tau, and 3.6-fold and 29-fold, respectively, by roIFN-tau. The stimulation resulted in a net increase in the PGE2:PGF2alpha ratio of 7.7 with rbIFN-tau and 5.1 with roIFN-tau at the optimal concentration of 1 microg/ml (p < 0.0001). By contrast, addition of OT (100 nM) alone resulted in a decrease of the PGE2:PGF2alpha ratio. The level of stimulation of PGE2 by IFN-tau was reduced in the presence of OT, showing that there was some interaction between OT and IFN-tau at the cellular level in the regulation of PG production. In uterine stromal cells, roIFN-tau and rbIFN-tau stimulated PGE2 and PGF2alpha production 12-fold (p < 0.0001). The ratio of PGE2:PGF2alpha was not affected in a dose-dependent manner, but was increased (p < 0.001) at a single dose of rbIFN-tau (0.001 microg/ml) and roIFN-tau (0.01 microg/ml). The results indicate that 1) bovine endometrial cells are more responsive to rbIFN-tau than to roIFN-tau, 2) rIFN-tau regulates PGs by stimulating PGE2 preferentially, and 3) rIFN-tau transforms the response to OT from stimulation of PGF2alpha to stimulation of PGE2.
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PMID:Recombinant ovine and bovine interferons tau regulate prostaglandin production and oxytocin response in cultured bovine endometrial cells. 911 39

This review considers the potential reduction of embryo mortality in vitro and in vivo in ruminants. Data on cytokines provided by different fields of reproductive immunology and biology were collated. Because of the crucial importance of the local interactions between the embryo and its dam, the expression of growth-factor and cytokine genes was analysed in the embryo proper, trophoblast, oviduct and endometrium by reverse transcriptase polymerase chain reaction in sheep and in cattle during the pre- and periimplantation periods. Many deleterious cytokines, such as tumour necrosis factor-alpha, interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and beneficial cytokines, such as transforming growth factor-beta, leukaemia inhibiting factor, colony-stimulating factor-1 (CSF-1), granulocyte-macrophage CSF, IL-1, IL-3, IL-4, IL-6, IL-10 and IFN-tau appeared to be involved in embryo survival in ruminants and other species. Their administration is efficient in a murine experimental model (CBA/J x DBA/2) of embryonic and fetal mortality. For instance, recombinant ovine IFN-tau (roIFN-tau) injected at the moment of implantation drastically reduces embryonic mortality in this model. In ruminants, roIFN-tau and recombinant bovine IFN-tau are very efficient in maintaining progesterone luteal secretion in cyclic animals. The involvement of IFN-tau in the mechanisms of maternal pregnancy recognition are particularly detailed in relation to inhibition of 13,14 dihydro-15-keto-prostaglandin F2 alpha (PGFM) pulses and oxytocin uterine receptivity. A synthetic model of the anti-luteolytic effects of IFN-tau on the endometrial cell is proposed. Finally, the particular potential of serum pregnancy-specific proteins (PSPs: PSPB, PSP60, pregnancy-associated glycoprotein) for monitoring embryo survival, with examples given for cattle and sheep is underlined.
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PMID:Recent developments and potentialities for reducing embryo mortality in ruminants: the role of IFN-tau and other cytokines in early pregnancy. 926 83

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