Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon tau (IFN tau) is the conceptus-produced antiluteolytic signal in ruminants. Three experiments examined the effects of s.c. administration of recombinant ovine (ro)IFN tau on interestrous interval (IEI), oxytocin (OT)-induced uterine prostaglandin F2alpha metabolite (PGFM) production, rectal temperature (RT), respiration rate (RR), and plasma concentrations of progesterone, cortisol, LH, and antiviral activity (AVA) in plasma and uterine flushings. In experiment I, 20 ewes were treated s.c. with either 0, 1, 2, or 4 mg/day roIFN tau (0.7 x 10(8) U/mg; 5 ewes/dosage) from Days 11 to 15 of the estrous cycle (estrus = Day 0) and were challenged with OT (30 IU) on Day 15. Jugular blood samples were collected at -10, 0, 10, 20, 30, 40, 50, and 60 min relative to the OT challenge and assayed for PGFM. Recombinant oIFN tau increased IEI (16.7, 18.7, and 22.6 +/- 0.6 days for 0, 2, and 4 mg roIFN tau, respectively, p < 0.01). Recombinant oIFN tau did not affect peak PGFM response to OT (2309 +/- 172 pg/ml; p > 0.1). However, the 4 mg/day dosage delayed the time to peak PGFM (32.4 vs. 47.5 +/- 3.4 min; p < 0.01, 0 vs. 4 mg) and resulted in approximately 200% higher concentrations of PGFM at 60 min post-OT (0 vs. 4 mg/day, p < 0.07). Experiment II was similar to experiment I, except that only the 0- and 4-mg/day dosages of roIFN tau were administered. Ewes were hysterectomized on Day 16, and assay of uterine flushes detected no AVA from ewes treated with either 0 or 4 mg/day roIFN tau. In experiment III, 20 ewes were treated s.c. with either 0, 2, 4, or 6 mg roIFN tau on Day 12. Blood samples, RT, and RR were obtained at frequent intervals for 24 h, and plasma was assayed for progesterone, cortisol, LH, and AVA. Plasma AVA, which increased in a dose-dependent manner, was detectable within 60 min and remained elevated at 24 h compared to control values. RT (elevated 0.5-1.0 degrees C), RR, and cortisol increased in response to all dosages of roIFN tau, with peak values occurring 150-180 min postinjection. For all dosages of roIFN tau, plasma progesterone declined from 120 to 360 min posttreatment and then returned to pretreatment values by 24 h (p < 0.01) as compared to controls. Overall, exogenous roIFN tau altered uterine PGFM response to OT from a pulse to a gradual and sustained elevation and extended IEI with only a transient decline in progesterone and mild hyperthermia, effects that are not expected to compromise pregnancy.
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PMID:Effects of exogenous recombinant ovine interferon tau on circulating concentrations of progesterone, cortisol, luteinizing hormone, and antiviral activity; interestrous interval; rectal temperature; and uterine response to oxytocin in cyclic ewes. 928

Caruncules are differentiated sites of the endometrium in which placentation occurs in ruminants. We investigated whether the response to agents involved at the time of recognition of pregnancy differed in the caruncular (CAR) and inter-caruncular (ICAR) areas of the endometrium in vitro. The specialization in prostaglandin (PG) production previously described in cells from whole endometrium was reproduced in the CAR and ICAR areas: PGF2alpha and PGE2 were produced in greater proportions, respectively, in epithelial and stromal cells. The relative production of PGE2 was equivalent in epithelial cells from CAR and ICAR regions, but the production of PGF2alpha was higher (p < 0.05) in the ICAR region (2.2 +/- 0.5 vs. 4.0 +/- 0.2 ng/ microg DNA, respectively). In stromal cells, the ICAR area produced more PGE2 than did the CAR area (3.4 +/- 0.4 vs. 2.1 +/- 0.4 ng/ microg DNA, p < 0.05), and the respective PGE2:PGF2alpha ratio was significantly higher in the ICAR area (p < 0.05). The production of PGs was measured first in response to oxytocin (OT, 10(-9) to 10(-5) M) and then to recombinant ovine interferon-tau (roIFN-tau, 0.02 to 20 microg/ml) in a separate set of experiments. In epithelial cells, OT stimulated the production of PGF2alpha 6.3-fold in the CAR area and more than 33.0-fold in the ICAR area (7.1 +/- 3.2 vs. 36.3 +/- 9.8 ng/ microg DNA, respectively, p < 0.05). Production of PGE2 was also increased in both regions and reached a plateau at 4.1 +/- 0.4 ng/ microg DNA. In epithelial cells from the ICAR but not the CAR region, the PGE2:PGF2alpha ratio was decreased in the presence of OT (p < 0.05). In separate experiments, addition of roIFN-tau stimulated PGE2 production significantly (p < 0.05), and no difference (p > 0.8) was observed between CAR and ICAR regions. An increase in PGE2:PGF2alpha ratio was observed in epithelial cells from both CAR and ICAR regions, but it was significant only in the CAR region (p < 0.05). In stromal cells, roIFN-tau stimulated PGE2 production significantly in cells from the CAR and ICAR regions (35.6 +/- 2.9 vs. 24.1 +/- 3.8 ng/ microg DNA, respectively, p < 0.05). In summary, the ICAR region seems to be the privileged site for regulation of PGF2alpha production by OT, but the caruncules may be a preferred site for recognition of the embryonic IFN-tau signal. Endometrial cells from the CAR and ICAR areas appear to exhibit specialized responses, with cells from the ICAR region more responsive to OT and those from the CAR region more sensitive to roIFN-tau.
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PMID:In vitro response to oxytocin and interferon-Tau in bovine endometrial cells from caruncular and inter-caruncular areas. 968 91

IFN-tau (IFN-tau) constitutes a new class of type I IFN which is not virus-inducible, unlike IFN-alpha and IFN-beta, but is constitutively produced by the trophectoderm of the ruminant conceptus during a very short period in early pregnancy. It plays a pivotal role in the mechanisms of maternal recognition of pregnancy in ruminants and it displays high antiviral and antiproliferative activities across species with a prominent lack of cytotoxicity at high concentrations in vitro in cell culture and possibly in vivo. It exhibits high antiretroviral activity against HIV and exhibits immunosuppressive activity in a multiple sclerosis model and reduces embryo and fetal mortality by stimulation of IL-10 production. In this review all the biochemical and para-hormonal properties of this novel IFN-tau are described in detail: structural characteristics of proteins and genes, trophoblast expression, regulation of its expression, structure of its gene promoter, its absence in human species and in non-ruminant animals, the evolution of the IFN-tau genes, its structure-function relationships with its three-dimensional structure, structural localization of biological activities, its lack of cytotoxicity and its receptor. Surprisingly, for an IFN, IFN-tau is also a pregnancy-embryonic signal with paracrine antiluteolytic activity. In order to maintain luteal progesterone secretion, IFN-tau inhibits PGF-2alpha pulsatile secretion and oxytocin uterine receptivity in early pregnancy. It is believed to suppress pulsatile release of endometrial PGF-2alpha by preventing oxytocin and estrogen receptor expression. Additionally, it directly regulates prostaglandin metabolism and possibly the PGE:PGF-2alpha ratio.
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PMID:IFN-tau: a novel subtype I IFN1. Structural characteristics, non-ubiquitous expression, structure-function relationships, a pregnancy hormonal embryonic signal and cross-species therapeutic potentialities. 986 98

Oxytocin (OT) is responsible for the episodic release of luteolytic prostaglandin (PG) F2alpha from the uterus in ruminants. The attenuation of OT-stimulated uterine PGF2alpha secretion by interferon-tau (IFN-tau) is essential for prevention of luteolysis during pregnancy in cows. To better understand the mechanisms involved, the effect of recombinant bovine IFN-tau (rbIFN-tau) on OT-induced PG production and cyclooxygenase-2 (COX-2) and PGF synthase (PGFS) expression in cultured endometrial epithelial cells was investigated. Cells were obtained from cows at Days 1-3 of the estrous cycle and cultured to confluence in RPMI medium supplemented with 5% steroid-free fetal calf serum. The cells were then incubated in the presence or absence of either 100 ng/ml OT or OT+100 ng/ml rbIFN-tau for 3, 6, 12, and 24 h. OT significantly increased PGF2alpha and PGE2 secretion at all time points (p < 0.01), while rbIFN-tau inhibited the OT-induced PG production and reduced OT receptor binding in a time-dependent manner. OT increased the steady-state level of COX-2 mRNA, measured by Northern blot, which was maximal at 3 h (9-fold increase) and then decreased with time (p < 0.01). OT also caused an increase in COX-2 protein, which peaked at 12 h (11-fold increase), as measured by Western blot. Addition of rbIFN-tau suppressed the induction of COX-2 mRNA (89%, p < 0.01) and COX-2 protein (50%, p < 0.01) by OT. OT also increased PGFS mRNA, and this stimulation was attenuated by rbIFN-tau (p < 0.01). To ensure that the decrease in COX-2 was not solely due to down-regulation of the OT receptor, cells were stimulated with a phorbol ester (phorbol 12-myristate 13-acetate; PMA) in the presence and absence of rbIFN-tau. The results showed that rbIFN-tau also decreased PMA-stimulated PG production and COX-2 protein. It can be concluded that rbIFN-tau inhibition of OT-stimulated PG production is due to down-regulation of OT receptor, COX-2, and PGFS.
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PMID:Down-regulation of oxytocin-induced cyclooxygenase-2 and prostaglandin F synthase expression by interferon-tau in bovine endometrial cells. 1002 13

Pulsatile release of uterine prostaglandin F2alpha (PGF2alpha) induces luteolysis in ruminants. However, the mechanism(s) that initiates and maintains luteolysis has not been defined. The present study tested the hypothesis that the endogenous PGF2alpha pulse generator is uterine-derived platelet-activating factor (PAF). Ovariectomized ewes were given exogenous progesterone (P), estradiol (E), or both (P+E, mimicking the normal luteal phase). Only ewes treated with steroids released PAF into the uterine lumen and had increased PAF:acetylhydrolase activity in the uterine lumen. Steroid treatment also influenced the capacity of the uterus to release PGF2alpha in response to exogenous PAF. PAF infusion did not affect plasma PGF2alpha metabolite (PGFM) levels in control (no steroid treatment) ewes but increased plasma PGFM levels in P+E ewes (P < 0.001) and ewes treated with P or E alone (P < 0.05). Infusion of PAF followed by or coincident with oxytocin (OT) acted in a synergistic manner to increase plasma PGFM levels. Repeated infusion of PAF into the uterus at 1-h intervals induced tachyphylaxis of the PGFM response to PAF; however, sensitivity of the uterus to PAF returned spontaneously by the 6th h. Interferon-tau (IFN-tau) inhibits pulsatile release of PGF2alpha during pregnancy to prevent luteolysis. Exogenous recombinant ovine IFN-tau (50 microgram) inhibited the uterine response to PAF alone or the combined effects of PAF and OT. These results indicate that uterine PAF fulfills many of the criteria for an endogenous PGF2alpha pulse-generator: steroid induction of PAF production and uterine responsiveness to PAF-induced release of PGF; synergistic stimulation of PAF-induced PGF release by OT; inhibition of PAF effects by IFN-tau; and PAF's ability to induce pulses of PGF with a periodicity during a period of chronic exposure of the uterus to PAF.
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PMID:Platelet-activating factor may act as an endogenous pulse generator for sheep of luteolytic PGF2alpha release. 1019 17

Interferon tau (IFNtau) is the antiluteolytic signal produced by the conceptus of ruminants. Intrauterine administration of recombinant ovine IFNtau suppresses expression of endometrial estrogen receptor (ER) and oxytocin receptor (OTR) in the luminal and superficial glandular epithelia to abrogate the production of luteolytic prostaglandin F(2alpha) (PGF(2alpha)) pulses. Subcutaneous (s.c.) injections of recombinant ovine (o) IFNtau appear to extend the interestrous interval by altering uterine PGF(2alpha) response to oxytocin. The present study tested the hypothesis that antiluteolytic effects of roIFNtau injected into the uterine lumen (paracrine) or s.c. (endocrine) are equivalent in suppressing expression of endometrial ER and OTR and inducing uterine expression of type I IFN-regulated Mx and ubiquitin cross-reactive proteins (UCRP). Sixteen cyclic ewes were fitted with uterine catheters on Day 5 (Day 0 = estrus), were assigned randomly to receive treatment with control proteins or roIFNtau (2 x 10(7) antiviral units/day) by either intrauterine or s.c. injections from Days 11 to 15, and were ovariohysterectomized on Day 16. Results indicated that expression of ER and OTR mRNAs in endometrial epithelium was suppressed by intrauterine but not by s.c. injections of roIFNtau. Intrauterine injections of roIFNtau increased expression of Mx and UCRP mRNA in the endometrium. Subcutaneous injections of roIFNtau increased endometrial Mx mRNA levels but not UCRP mRNA. Unexpectedly, intrauterine and s.c. injections of roIFNtau were equally effective in inducing expression of Mx and UCRP mRNA in the corpus luteum. Although s.c. injections of roIFNtau induced Mx mRNA in the endometrial epithelium, s.c. injections of roIFNtau did not abrogate activation of the uterine luteolytic mechanism by suppressing epithelial ER and OTR expression. Therefore, results of this study failed to support the assumption that endocrine roIFNtau mimics antiluteolytic effects of paracrine IFNtau to improve pregnancy rates in sheep.
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PMID:Differential effects of intrauterine and subcutaneous administration of recombinant ovine interferon tau on the endometrium of cyclic ewes. 1041 28

During reproductive processes, prostaglandin (PG) E(2) (PGE(2)) and PGF(2alpha) play important roles in which they often exert opposite effects. At the time of recognition of pregnancy in vivo, PGF(2alpha) is recognized as the luteolytic factor in ruminants and in most species including human, whereas PGE(2) may exert a luteoprotective action. We have previously demonstrated that recombinant interferon-tau (rIFN-tau), the embryonic signal responsible for recognition of pregnancy in ruminants, stimulated in vitro the production of PGE(2) and prostaglandin-endoperoxide synthase 2 (Ptgs2; also called cyclooxygenase-2) gene expression in both epithelial and stromal endometrial cells. Since PGE(2) is the major prostaglandin produced by stromal cells, the effect on Ptgs2 could explain the increase in PGE(2) output. At high concentrations, however, recombinant ovine (ro) IFN-tau acts on epithelial cells by changing the primary PG produced from PGF(2alpha) to PGE(2). This change in the primary PG produced could be explained by a decrease in PGF synthase (PGFS) activity or an increase in PGE synthase activity, or by modulation of a putative PGE(2)-9-ketoreductase, which converts PGE(2) into PGF(2alpha). Therefore, we have investigated the regulation of the mRNAs for PGFS and PGE(2)-9-ketoreductase (9K-PGR), two enzymes that lead to the production of PGF(2alpha). Others have described 9K-PGR activity in uterus, ovaries, kidney, and liver of different species and have established that this enzyme could possess both 9K-PGR and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) activity. Some have concluded that 9K-PGR and 20alpha-HSD are identical enzymes. Using primers sequences chosen from homologous nucleotide sequences of published rabbit 20alpha-HSD/9K-PGR and rat 20alpha-HSD cDNAs, a 317-base pair (bp) fragment was amplified by reverse transcription-polymerase chain reaction (RT-PCR), cloned, and sequenced. Homologies of 83% and 78% were found with rabbit and rat 20alpha-HSD, respectively. The presence of 20alpha-HSD/9K-PGR and prostaglandin F synthase (PGFS) mRNA expression was studied semiquantitatively in cultured epithelial cells using RT-PCR. Stimulation of cells with roIFN-t resulted in a biphasic response, an inhibition of PGF(2alpha) production at low dose (1 ng/ml) and a stimulation of PGE(2) at high dose (10 microg/ml). The increase of PGE(2) was accompanied by reduced 9K-PGR and PGFS mRNA gene expression. The effect of oxytocin (OT) was also studied, and the presence of OT had no effect on either 9K-PGR or PGFS gene expression. The 20alpha-HSD/9K-PGR transcript was also detected in other bovine tissues at different intensity (liver > kidney > testis > ovaries). We believe that the 9K-PGR and PGFS can be key enzymes in the regulation of specific PGs in the endometrium during the periimplantation period.
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PMID:Detection and regulation of the messenger for a putative bovine endometrial 9-keto-prostaglandin E(2) reductase: effect of oxytocin and interferon-tau. 1061 Oct 76

Six conceptuses were collected from red deer hinds on day 22 after synchronization of oestrus with intravaginal progesterone-releasing devices (removal of device = day 0). Within 24 h of culture in vitro, the supernatant from five of six conceptuses showed detectable antiviral activity. Interferon alpha (IFN-alpha) receptors were identified by immunohistochemistry on the luminal surface of the endometrium, in the neurohypophysis and paraventricular hypothalamus, but not in the ovaries of the hinds from which the conceptuses were collected. Another 16 intact hinds were synchronized as above. Injection of 4 mg IFN i.m. twice a day on days 13-15 had no effect on cloprostenol-induced oxytocin secretion on day 15 and did not prevent cloprostenol-induced luteal regression. Sixteen ovariectomized hinds received a protocol of steroid treatment to mimic ovarian hormone secretion during the normal oestrous cycle. On day 16, hinds showed undulant oxytocin secretion that showed a degree of temporal association with uterine PGF2 alpha release. Treatment with 4 mg IFN-alpha I 1 twice a day on days 13-16 had no effect on this spontaneous oxytocin secretion, but reduced the magnitude of cloprostenol-induced oxytocin secretion on day 17 (P < 0.05). These results indicate that red deer conceptuses secrete an anti-luteolytic IFN to which the endometrium expresses a receptor during early pregnancy. The presence of IFN receptors in the hypothalamus and posterior pituitary and the IFN-induced suppression of extra-ovarian oxytocin secretion provides tentative evidence of an involvement of the central nervous system in maternal recognition of pregnancy in deer.
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PMID:Source and site of action of anti-luteolytic interferon in red deer (Cervus elaphus): possible involvement of extra-ovarian oxytocin secretion in maternal recognition of pregnancy. 1061 55

Objectives were to examine how the conceptus and recombinant bovine interferon-tau (rbIFN-tau) regulate intracellular components of the PGF(2a) synthetic pathway and to determine if arachidonic acid (AA) is limiting in endometrial tissue of pregnant cows. In Experiment 1, uteri were collected from either cyclic or pregnant dairy cows on Day 17 post-estrus. Intercaruncular explants were dissected and incubated for 60 min to quantify PGF(2a) production in response to oxytocin (10(-6) M), A23187 (10(-5) M), melittin (10(-5) M), and phorbol 12, 13 dibutyrate (PDBu, 10(-6) M). Additional explants from the same cows were incubated for 24 h with and without AA. Oxytocin and A23187 did not stimulate PGF(2a) in explants from either cyclic or pregnant cows. Both PDBu, melittin, and A23187 + melittin stimulated PGF(2a) production in explants of cyclic cows, but not in explants of pregnant cows. The addition of AA to explant cultures for 24 hr did not increase PGF(2a) production during a subsequent 60-min incubation. In Experiment 2, explants were collected from cows that received intrauterine infusions of either BSA (1.9 mg/1.2 ml) or rbIFN-tau (0.2 mg rbIFN-tau + 1.7 mg BSA/1.2 ml) twice a day from Days 14 to 17 of the estrous cycle. Treatments of rbIFN-tau attenuated PGF(2a) secretion induced by in vitro PDBu and A23187 treatments. However, rbIFN-tau treatment in vivo had no effect on the in vitro induction of PGF(2a) secretion by melittin. IFN-tau may regulate the PGF(2a) synthetic pathway by reducing activity of PKC or PKC mediated events.
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PMID:Intracellular regulation of endometrial PGF(2a) and PGE(2) production in dairy cows during early pregnancy and following treatment with recombinant interferon-tau. 1076 76

The maternal recognition of pregnancy in ruminants requires the production of interferons by the preimplantation blastocyst. These proteins, the trophoblast interferons (IFN-tau), are the products of a number of similar genes, the expression of which is controlled by characteristic promoter regions. They are expressed for a short period in high concentrations, and have antiluteolytic, antiviral, antiproliferative and immunomodulatory effects, through receptors on the endometrial epithelium. The antiluteolytic effects of IFN-tau result from inhibition of endometrial expression of the oxytocin receptor, through which circulating oxytocin stimulates episodic prostaglandin F2a production. Some of the properties of IFN-tau differ from those of other type I interferons, and they may have novel therapeutic effects. Because of their central role in early gestation, these proteins have excited the interest of reproductive physiologists. However, their other properties, and the fact that their expression is controlled so precisely, have made them of interest to a wide range of biologists.
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PMID:Trophoblast interferon and pregnancy. 1122 28


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