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)

The uterus is a primary target for sex steroid action in vivo during the estrous cycle and pregnancy. Cell cultures have been used to determine the specific function of the different cell types forming the uterus. We used endometrial cell cultures previously characterized in our laboratory to study the effect of estradiol (E) and progesterone (P4) on prostaglandin (PG) production and on regulation of the response of the cells to oxytocin (OT). The studies were performed on confluent cultures of epithelial cells grown as a monolayer either on plastic or on filter inserts to allow basal-apical polarization. As described previously, prostaglandin F2 alpha (PGF 2 alpha) production was greater (3.7-fold, p < 0.0001) than prostaglandin E2 (PGE2) production in epithelial cells, and the opposite was true in stromal cells (PGE2 9.9-fold > PGF2 alpha, p < 0.0001). In epithelial cells, the basal production of PGE2 (-61.6%, p < 0.0001) and PGF2 alpha (-51.7%, p < 0.0001) was reduced significantly by E and increased significantly by P4 (PGE2, + 30.0% [p < 0.002]; PGF2 alpha, + 22.2% [p < 0.006]). No significant effect of sex steroids on the basal production of PGs was detected in stromal cells. OT stimulated the production of PGF2 alpha (6.7-fold, p < 0.0001) and PGE2 (9.1-fold, p < 0.0001) in epithelial but not stromal cells. Treatment of the cells with E significantly (p < 0.001) increased OT-stimulated PGF2 alpha production in both the epithelial and stromal cells and that of PGE2 in epithelial cells only. The effect of steroids and OT was similar in polarized (filter) and nonpolarized (plastic) epithelial cells. Analysis of the vectorial secretion of PGs in epithelial cells grown on filter inserts revealed that PGF2 alpha is preferentially secreted in the basal (p < 0.001) compared to the apical compartment. The direction of secretion was not influenced by steroid or OT treatments. The results suggest that epithelial cells of the endometrium are a preferred target for the regulation of PG synthesis by sex steroids and OT.
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PMID:Influence of sex steroids on the production of prostaglandins F2 alpha and E2 and response to oxytocin in cultured epithelial and stromal cells of the bovine endometrium. 878 88

Endometrial oxytocin receptors and total production of PGF by endometrial epithelial cells were measured in 10 cyclic cows after intrauterine injections of recombinant bovine interferon-tau plus BSA or BSA alone. Cows received twice daily injections (via intrauterine catheters) of 200 micrograms of recombinant bovine interferon-tau plus 1.3 mg of BSA (n = 5) or 1.5 mg of BSA (n = 5) from d 14 to 17 after estrus. On d 17, the reproductive tracts of each cow was removed at slaughter, and endometrial epithelial cells were cultured with 0, 2, or 50 ng/ml of recombinant bovine interferon-tau. After 24 h, oxytocin (2 x 10(-7) M) was added to one-half of the culture wells, and the medium was sampled at 0, 30, and 90 min for analysis of total PGF (PGF plus 13, 14-dihydro-15-keto-PGF2 alpha). In vivo treatment with recombinant bovine interferon-tau + BSA reduced total secretion of PGF in culture (1.49 +/- 0.06 vs. 2.80 +/- 0.07 ng/micrograms of DNA), but did not block the oxytocin-induced stimulation in total secretion of PGF. In vitro treatment of cells with recombinant-bovine interferon-tau did not decrease basal secretion of total PGF. Oxytocin receptor binding at d 17 was low in both treatments but slightly attenuated in the group treated with recombinant bovine interferon-tau.
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PMID:Treatment with recombinant bovine interferon-tau in utero attenuates secretion of prostaglandin F from cultured endometrial epithelial cells. 888 Apr 61

In previous studies in our laboratory, we demonstrated that oxytocin (oxy) augmented prostaglandin F(2alpha) (PGF(2alpha)) synthesis via enhancing the uptake of Ca2+ by uterine tissue. On the other hand, we have shown that oxy enhances PGF(2alpha) synthesis in uterine and ovarian tissues during the corpus luteum (CL) regression in the rat. In the present study we explore the possible relation between endogenous nitric oxide (NO) and oxy on PGs synthesis during the luteolytic phase in the rat. The experiments were done in uterine and ovarian preparations isolated from pseudopregnant (psp) rats during the luteolytic phase. Tissues were incubated "in vitro" with 1)- oxy (50 mU/ml), 2)-NMMA (N(G)-monomethyl-L-arginine), a potent NOs inhibitor (300 uM), and 3)- both reagents (oxy + NMMA). NMMA decreases the synthesis of both PGs (PGE and PGF(2alpha)) and oxy enhances PGF(2alpha) synthesis in uterine and ovarian tissue. When reagents were used in combination (oxy + NMMA), we found different results in uterus and ovaries; i.e., in uterine tissue the NO inhibition did not affect the increase of PGF(2alpha) synthesis by oxy. Meanwhile, in ovaries the oxy effect over the PGF(2alpha) synthesis was not seen when NOs was inhibited. Probably oxy acts via different mechanisms on PGF(2alpha) synthesis in uterine and ovarian tissue. This assumption was confirmed when the NOs activity in both tissues (uterine and ovarian) was measured after oxy treatment. We found that oxy enhanced the NOs activity in ovarian tissues from psp rats but did not modify the enzyme activity in uterine tissue.
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PMID:Role of nitric oxide on uterine and ovarian prostaglandin synthesis during luteolysis in the rat. 915 Mar 71

The primary objective was to examine the effects of estradiol and the progesterone receptor antagonist onapristone on the pulsatile secretion of prostaglandin F(2alpha) (PGF(2alpha)) and ovarian and pituitary oxytocin. A 2 x 2 factorial arrangement of estradiol and onapristone treatments was administered to groups of 5 ewes after destruction of ovarian follicles on Day 8 of the cycle. Estradiol treatments consisted of the administration of a silicone elastomer implant, either containing or not containing estradiol, on Day 8 plus 50 microg of estradiol or corn oil on Days 11 and 12. Onapristone (2 mg/kg) or its vehicle were administered on Day 13, immediately preceding the simultaneous collection of blood samples from the carotid artery, jugular vein, and vena cava at 7.5-min intervals for 7 h. Ewes were immediately killed for measurements of uterine oxytocin receptor concentrations and phosphatidylinositide turnover. More oxytocin pulses were detected in the jugular vein than in the carotid artery (p < 0.01), suggesting that the pituitary is a source of oxytocin. A similar number (p > 0.1) of PGF(2alpha) pulses were correlated with oxytocin pulses as were not. The linked PGF(2alpha) pulses were longer in duration (p = 0.01) with a tendency toward a higher amplitude (p = 0.08). The corresponding vena caval oxytocin pulses had a longer duration (p = 0.02) than those not linked to PGF(2alpha). Estradiol increased oxytocin receptor concentrations and the turnover of phosphatidylinositides (p = 0.02) without affecting PGF(2alpha) pulse characteristics. Onapristone increased (p = 0.03) PGF(2alpha) pulse amplitude. Although a lower than expected temporal correlation between oxytocin and PGF(2alpha) pulses was observed, the distinguishing characteristics of linked pulses may be indicative of their physiological significance.
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PMID:Influence of estradiol and progesterone withdrawal on the secretion of and the temporal correlation between pulses of oxytocin and prostaglandin F2(alpha) in ewes. 916 Jul 23

A microdialysis system (MDS) was surgically implanted into the corpora lutea (CL) of 12 normally cycling Holstein heifers. Heifers were either allowed to undergo spontaneous luteolysis (Spontaneous, n = 6) or received an intramuscular injection of prostaglandin F2 alpha (PGF2 alpha) on Day 12 of the estrous cycle (Induced, n = 6). The MDS was implanted on Day 11 in the induced heifers and on Day 17 in Spontaneous heifers. CL were perfused with Ringer's solution at a flow rate of 3 ml/hr beginning immediately after surgery. Dialysate samples were collected hourly for 3-4 days. Samples were assayed for progesterone (P4), oxytocin (OT), PGF, and leukotrienes B (LTB) and C (LTC). Dialysate OT was undetected in all but one Spontaneous and one induced heifer. Lipoxygenase products of arachidonic acid (AA) metabolism (LTB and LTC) in the dialysate were found to be closely associated with luteal regression. In Spontaneous heifers, the mean interval from the first hormone peak to the onset of P4 decline was similar for PGF, LTB, and LTC, with the first peak occurring at 12.8 +/- 8.1, 22.0 +/- 6.1, and 11.0 +/- 8.9 hr before the onset of P4 decline, respectively. The peak LTC value was greater (P < 0.05) than peak LTB or PGF. The 12-hr sampling interval with the highest LTC peak frequency was highly correlated (r = 1.0; P < 0.01) with the onset of P4 decline, but the highest LTB and PGF peak frequencies were not associated with the onset of P4 decline. Indeed, the mean numbers of PGF and LTB hormone peaks were higher (P < 0.05) after the onset of P4 decline than before. Administration of PGF2 alpha on Day 12 of the estrous cycle stimulated a decline in P4 secretion and an increase in the secretion of PGF, LTB, and LTC from the CL. In induced animals, the peak level of PGF was greater (P < 0.05) than peak LTB. These results suggest that the AA metabolites LTB and, especially, LTC play important roles during normal regression of the bovine CL.
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PMID:Roles of leukotrienes in bovine corpus luteum regression: an in vivo microdialysis study. 931 13

Oxytocin (OT) is the physiological stimulus for pulsatile release of endometrial prostaglandin (PG) F2alpha during luteolysis in domestic ungulates, and the cellular mechanism for this appears to involve phosphoinositide (PI) hydrolysis. To determine which endometrial cell type(s) was responsive to OT during luteolysis in swine, luminal epithelial (LEC), glandular epithelial (GEC), and stromal cells (SC) were isolated from endometrium by differential enzymatic digestion and sieve filtration on Day 16 postestrus and cultured. For PI hydrolysis in experiment 1, SC were most responsive to 100 nM OT (p < 0.001), whereas LEC were least responsive and GEC had an intermediate response (p < 0.001). For PGF secretion in experiment 2, the response to OT was greatest for SC, least for LEC, and intermediate for GEC. In experiment 3, 100 nM OT increased PI hydrolysis in SC within 30 min (p < 0.05) and in GEC within 60 min (p < 0.05) but did not increase PI hydrolysis in LEC. In experiment 4, PI hydrolysis in SC was increased (p < 0.05) by 33-333 nM OT but was not increased by </= 333 nM OT in GEC or LEC after 30 min. However, PGF secretion from SC was increased (p < 0.05) by 10-333 nM OT, and from GEC by 10-333 nM OT, but was not increased from LEC by </= 333 nM OT. Results of this study indicate that 1) there was differential responsiveness to OT among endometrial cell types, and 2) within cell type, there generally was a similar response to OT for both PI hydrolysis and PGF secretion, further implicating PI hydrolysis as the signaling pathway for OT-stimulated PGF2alpha release. The differential response of endometrial cell types may have an important role in the pattern of PGF2alpha secretion during luteolysis in swine.
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PMID:Oxytocin-stimulated phosphoinositide hydrolysis and prostaglandin F secretion by luminal epithelial, glandular epithelial, and stromal cells from pig endometrium. I. Response of cyclic pigs on day 16 postestrus. 978 Mar 35

The objective of these experiments was to determine the role of Ca2+ during oxytocin-stimulated prostaglandin (PG) F2 alpha release from bovine endometrial tissue in vitro. Uteri were collected from dairy cows on the day after spontaneous luteal regression. Caruncular endometrial explants were dissected and incubated in vitro to determine phospholipase C activity or PGF2 alpha release. A23,187 (a calcium ionophore) and maitotoxin (an activator of voltage-gated L-type calcium channels) stimulated release of PGF 2 alpha in a concentration-dependent manner (P < 0.05). Thapsigargin (induces accumulation of Ca2+ in the cytoplasm by inhibiting endoplasmic reticulum Ca2+/ATPase pumps) stimulated release of PGF2 alpha in a concentration-dependent manner as well (P < 0.13). Oxytocin (10(-6) M), AIF4- (a nonspecific activator of G-proteins; 10(-5) M), A23,187 (10(-5) M), and melittin (a stimulator of phospholipase A2; 10(-4) M) stimulated PGF2 alpha release when explants were incubated in Ca(2+)-free medium (P < 0.10); however, oxytocin, A23,187, or melittin were unable to stimulate PGF2 alpha release when explants were incubated in Ca(2+)-free medium containing the calcium chelator EGTA (P < 0.10). This treatment did not prevent oxytocin or AIF4- from stimulating phospholipase C activity (P < 0.08). CoCl2 (a nonspecific Ca2+ channel blocker) and methoxyverapamil (a specific voltage-gated L-type Ca2+ channel blocker) prevented oxytocin from stimulating PGF2 alpha release (P < 0.05). Our results suggest that both extracellular and intracellular Ca2+ may be required for oxytocin to stimulate PGF2 alpha secretion in bovine endometrial tissue.
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PMID:Cellular mechanisms by which oxytocin mediates uterine prostaglandin F2 alpha synthesis in bovine endometrium: role of calcium. 986 39

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

Female mice lacking the receptor for prostaglandin F2 alpha (FP) do not deliver fetuses at term, although these can be successfully rescued by cesarean section. No induction of oxytocin receptor mRNA is found in the uterus of these mice, and they show no uterine contraction on intravenous administration of oxytocin. Furthermore, a decline in serum progesterone levels during the periparturition period is not observed in these animals. Ovariectomy at day 19 of pregnancy restored induction of the oxytocin receptor and caused successful delivery in these animals. These results indicate not only the essential role of luteolytic PGF 2 alpha action in natural parturition but also the importance of oxytocin receptor induction in this process.
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PMID:Female reproduction in mice lacking the prostaglandin F receptor. Roles of prostaglandin and oxytocin receptors in parturition. 1002 19

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