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

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

Caprine uterine epithelial (UE) cells were cultured on Matrigel-coated filters. Transmission electron microscopy revealed polarized UE cells characterized by basally located nuclei, apical microvilli, convoluted lateral membranes, and junctional complexes. Domain-specific secretion of prostaglandins and radiolabeled proteins provide further evidence of functional epithelial cell polarity. Two experiments were conducted to evaluate factors controlling prostaglandin E2 (PGE) and prostaglandin F2alpha (PGF) secretion. In experiment one, steroid-treated (estradiol, progesterone, or estradiol + progesterone) polarized UE cells were treated with interferon tau (IFNtau) and/or oxytocin (OT). Steroid treatment did not influence PGE or PGF secretion. However, analysis of variance revealed an IFNtau by OT interaction (P < .01) for both PGE and PGF This interaction was caused by a reduction in PGE and PGF secretion by cultures receiving only IFNtau and the inability of IFNtau to block OT-induced release of PGE or PGF. In experiment 2, polarized UE cells were cultured in progesterone, with or without IFNtau, and sequentially challenged with estradiol and OT. Oxytocin stimulated the release of both PGE and PGF by polarized cUE cells (P < .01) and resulted in an increased accumulation of PGE (OT*domain; P < .01) in the basal compartment. Interferon tau did not influence PGE (P < .1) secretion. However, further analysis revealed that IFNtau reduced PGF secretion and was unable to block OT-induced PGF secretion (IFNtau*OT; P < .05) by polarized UE cells. Therefore, caprine UE cells form polarized monolayers and retain responsiveness to IFNtau and OT in vitro.
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PMID:Regulation of protein and prostaglandin secretion in polarized primary cultures of caprine uterine epithelial cells. 971 18

The expression of oxytocin receptor (OTR) in the uterine endometrium plays an important role in the initiation of luteolysis. During early pregnancy, the conceptus secretes interferon tau (IFN|gt) which inhibits OTR up-regulation and luteolysis. In this study, uterine horn cross sections were collected on day 16 from 15 pregnant cows (PREG), 9 uninseminated controls and 5 inseminated cows with no embryo present. The latter two groups had similar results and were combined to form a single non-pregnant (NP) group. The animals were given an oxytocin challenge shortly before tissue collection to assess prostaglandin F2alpha (PGF2alpha) release through the measurement of the metabolite 13,14-dihydro-15-keto PGF2alpha (PGFM). The mRNAs for OTR, oestrogen receptor (ER) and progesterone receptor (PR) were localised by in situ hybridisation. The results were quantified by optical density (OD) measurements from autoradiographs using image analysis. OTR protein was measured by autoradiography with iodinated oxytocin antagonist and ER and PR protein was detected by immunocytochemistry. The release of PGFM after the oxytocin challenge was significantly higher in the 14 NP cows (187%+/-15%) compared with the PREG group (131%+/-11%) (P<0.01). Low concentrations of OTR mRNA were localised to the luminal epithelium (LE) in 6 out of the 14 NP cows, of which 2 also expressed OTR protein, while OTR mRNA and protein were undetectable in all the pregnant animals. These results indicated that the sampling time coincided with the onset of the luteolytic mechanism in the NP cows. On day 16 ER mRNA was detectable in both the LE and glands of both PREG and NP animals. There were no differences in either ER mRNA or protein between NP and PREG samples. PR mRNA was moderately expressed in the caruncular stroma, with lower levels in the dense caruncular-like stroma and glands. There were no differences between PREG and NP animals. The expression of PR mRNA and protein in the deep glands was variable between animals. These results suggested that, in cows, the presence of an embryo suppressed the expression of OTR, but had no effect on the expression of the transcriptionally regulated ER on day 16.
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PMID:The effect of pregnancy on the expression of uterine oxytocin, oestrogen and progesterone receptors during early pregnancy in the cow. 985 73

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

Endometrial epithelial cell cultures were established from bovine uterine tissue collected during the oestrous cycle from commercially slaughtered animals. These cells were shown to express moderately high levels of oxytocin receptors (OTR) (up to 30000 per cell) after about one week in culture. These receptors have been characterized at the molecular, pharmacological and functional level and shown to be identical to those expressed in the bovine endometrium in vivo. Preliminary experiments to investigate the regulation of the OTR and its gene using this system, have shown that expression is to a large degree constitutive, the receptors being spontaneously upregulated during culture. Sex steroids at concentrations close to or above the serum limits observed in vivo appeared to have no effect, although the cells were shown to express mRNA for the specific steroid receptors throughout culture. Only the blastocyst product, interferon-tau, showed a significant effect, downregulating both OTR and their gene transcripts in the cultured endometrial epithelial cells. Although more extensive studies are necessary, these results support the view that the OTR gene is controlled in part at least by a combination of constitutive and inhibitory elements.
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PMID:Bovine endometrial epithelial cells as a model system to study oxytocin receptor regulation. 1002 14

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

During early pregnancy the bovine embryo must produce a protein called interferon tau which inhibits the development of the luteolytic mechanism. Failure to inhibit luteolysis is the major cause of pregnancy loss in cows. The embryo must produce sufficient quantities of interferon tau by about day 16 to prevent luteolysis. Its ability to achieve this is largely dependent on the pattern of maternal progesterone production. A late rise in progesterone after ovulation or poor progesterone secretion during the luteal phase results in the development of poor embryos capable of producing little or no interferon tau at the critical time. The embryo inhibits luteolysis by preventing development of oxytocin receptors on the luminal epithelium of the uterine endometrium and thus oxytocin-induced secretion of PGF2 alpha and by the induction of a prostaglandin synthesis inhibitor within the endometrium. In sheep it has been hypothesised that interferon tau acts to inhibit endometrial oestrogen receptors and thus oestrogen-induced up-regulation of oxytocin receptors. In cows, the embryo inhibits the development of oxytocin receptors and the initiation of luteolysis without causing any change in uterine oestrogen receptors. Thus in the cow, the mechanism by which interferon tau inhibits oxytocin receptor development remains to be determined.
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PMID:The regulation of interferon-tau production and uterine hormone receptors during early pregnancy. 1069 64

Early pregnancy is maintained in ruminants through the actions of conceptus-derived interferon (IFN)-tau on the endometrium. IFN-tau alters uterine release of PGF2 alpha' which results in rescue of the corpus luteum and continued release of progesterone. The mechanism of action of IFN-tau includes inhibition of oestradiol receptors, consequent reduction in oxytocin receptors, activation of a cyclooxygenase inhibitor, and a shift in the PGs to favour PGE2 over PGF2 alpha' IFN-tau also induces several endometrial proteins that may be critical for survival of the developing embryo. One endometrial protein induced by pregnancy and IFN-tau has been identified as bovine granulocyte chemotactic protein-2 (bGCP-2). This chemotactic cytokine (chemokine) has been used as a marker to delineate IFN-tau from IFN-alpha responses in the endometrium. A second protein, called ubiquitin cross-reactive protein (UCRP), resembles a tandem ubiquitin repeat. UCRP becomes conjugated to cytosolic endometrial proteins in response to IFN-tau and pregnancy. Proteins conjugated to UCRP are either modulated or targeted for processing through the proteasome. The action of IFN-tau is mediated by induction of signal transducer and activator of transcription 1 (STAT-1), STAT-2 and interferon regulatory factor 1 (IRF-1) transcription factors. Induction of these transcription factors, the alpha chemokines and UCRP is the prelude to maternal recognition of pregnancy in ruminants.
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PMID:Mechanism of action of interferon-tau in the uterus during early pregnancy. 1069 65

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

In this study, the relationship between maternal hormone environment and early embryo development in mature non-lactating Holstein-Friesian cows was investigated. Animals were inseminated at either 72 or 96 h after prostaglandin injection (n = 23) or were left as uninseminated controls (n = 10). Plasma samples were collected once a day from the first day of insemination (day 1) until day 16, when the cows underwent an oxytocin challenge, and were then slaughtered and their reproductive tracts removed. The tracts were flushed to collect embryos and the flushes were measured for interferon tau (IFN-tau) activity. Inseminated cows without an embryo on day 16 (n = 5) underwent both delayed ovulation (indicated by delayed decrease in oestradiol concentrations) and a delayed increase in progesterone concentrations after ovulation compared with cows with an embryo on day 16 (n = 15). Within the group of cows with an embryo, those with poorly developed embryos producing undetectable concentrations of IFN-tau (n = 7) had similar oestradiol profiles but underwent a delayed progesterone increase after ovulation compared with cows with well developed embryos producing measurable quantities of IFN-tau (n = 8). In the cows with an embryo, the plasma concentration of 13,14-dihydro-15-keto PGF2a, the principal metabolite of PGF2a, after injection of oxytocin was lower than that of control cows and cows without an embryo. However, when the cows with an embryo were compared on the basis of production of embryonic IFN-tau, the PGF2a response to oxytocin was attenuated completely in cows that had measurable IFN-tau activity, whereas a response of similar magnitude to that in control cows and cows without an embryo was observed in those with undetectable IFN-tau activities. In conclusion, the successful maternal recognition of pregnancy in cows depends on the presence of a sufficiently well developed embryo producing sufficient quantities of IFN-tau, which is, in turn, dependent on an appropriate pattern of maternal progesterone secretion.
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PMID:Relationship between maternal endocrine environment, early embryo development and inhibition of the luteolytic mechanism in cows. 1122 41


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