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

One of the classical biological actions mediated by the posterior pituitary hormone oxytocin (OT) is contraction of the uterus at parturition. Moreover, premature activation of the OT system is thought to contribute to preterm labor, a major clinical problem in obstetrical practice. However, the molecular mechanisms linking activation of the OT receptor (OTR) to myometrial contractions are not fully understood. Here, we describe an in vitro system that should serve as a useful tool to study this question at a cellular level. The system consists of a collagen lattice contraction assay and two different human myometrial cell lines: a cell clone from a telomerase-immortalized human myometrial cell population (hTERT-C3) as well as a cell line derived from a primary culture of human myometrial cells (M11). Using this approach, we observed that 1 nM OT promoted an almost maximal effect on cell contraction in both cell lines tested. Furthermore, this dose-dependent, OT-induced contraction was antagonized by the specific OTR antagonist d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr-NH(2)(9)]OVT as well as the clinically used antagonist atosiban. This cell line-based contraction assay enables the application of molecular tools aimed at suppressing or overexpressing specific genes. It is also amenable to high-throughput testing approaches. Therefore, this system represents a powerful and improved experimental model that should facilitate the study of the molecular signal transduction pathways involved in the uterotonic actions of OT.
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PMID:Novel in vitro system for functional assessment of oxytocin action. 1695 29

The nonapeptide oxytocin (OT) mediates a wide spectrum of biological action, many of them related to reproduction. Recently, we have shown that OT exerts a trophic effect on uterine smooth muscle cells and induces dephosphorylation, and thus activation, of the translation elongation factor eukaryotic elongation factor 2 (eEF2). The present study was designed to elucidate the mechanisms underlying this novel action of OT in the well-characterized human myometrial cell line hTERT-C3. Pathways known to induce eEF2 dephosphorylation are mammalian target of rapamycin (mTOR), and the MAPKs ERK1/2 and p38. Using a panel of chemical inhibitors of specific signaling pathways, we determined that none of these pathways played a role in OT-mediated eEF2 dephosphorylation. Because the OT receptor is a G protein-coupled receptor linked to Galphaq, we tested the possibility that this OT action was mediated via protein kinase C (PKC). PKC activity was blocked by application of the general PKC chemical inhibitor Go6983 or by incubation with the cell-permeable PKC inhibitor peptide myr-psi PKC. With either approach, the effect of OT on eEF2 dephosphorylation was suppressed, indicating that the PKC pathway is essential for this OT action. Consistent with this idea, we also found that direct stimulation of PKC with the phorbol ester phorbol 12-myristate 13-acetate induced eEF2 dephosphorylation. Moreover, we observed that the stimulatory effect of OT on [(35)S]methionine incorporation into nascent proteins was blocked by PKC inhibition. Overall, these results define a novel hormonal signaling pathway that leads to eEF2 dephosphorylation and activation of protein synthesis.
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PMID:Oxytocin-induced activation of eukaryotic elongation factor 2 in myometrial cells is mediated by protein kinase C. 1794 56

Activin is a pleiotropic growth factor with a broad pattern of tissue distribution that includes reproductive tissues. Although direct actions of activin have been described in gonadal and uterine tissues, actions in the myometrium have not been defined. In this study we have characterized the responsiveness of uterine tissue and myometrial cell lines to activin-A. Uterine tissue and two myometrial cell lines, PHM1 (pregnant human myometrial 1) and hTERT HM (telomerase reverse transcriptase-infected human myometrial) respond to activin-A as measured by phosphorylation of Smad-2. Those cell lines express a full complement of activin receptors, as well as activin beta(A) subunit and follistatin. Activin inhibited proliferation of PHM1 and human telomerase reverse transcriptase-infected human myometrial cell line cells, with more extensive growth inhibition observed in PHM1s. In PHM1s, activin-A decreased oxytocin receptor and HoxA-10 mRNA expression but did not alter total progesterone receptor, cyclooxygenase-2 (Cox-2), and connexin 43 mRNA expression levels. Furthermore, treatment of PHM1 myometrial cells with activin-A attenuated oxytocin and thromboxaneA2 induced intracellular Ca(2+) accumulation. In conclusion, myometrial cells are activin sensitive, and activin-A can regulate myometrial cell functions.
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PMID:Activin-A in myometrium: characterization of the actions on myometrial cells. 1823 71

The use of preparations from Bryophyllum pinnatum in tocolysis is supported by both clinical (retrospective comparative studies) and experimental (using uterus strips) evidence. We studied here the effect of B. pinnatum juice on the response of cultured human myometrial cells to stimulation by oxytocin, a hormone known to be involved in the control of uterine contractions by increasing the intracellular free calcium concentration ([Ca2+]i). In this work, [Ca2+]i was measured online during stimulation of human myometrial cells (hTERT-C3 and M11) with oxytocin, which had been pre-incubated in the absence or in the presence of B. pinnatum juice. Since no functional voltage-gated Ca2+ channels could be detected in these myometrial cells, the effect of B. pinnatum juice was as well studied in SH-SY5Y neuroblastoma cells, which are known to have such channels and can be depolarised with KCl. B. pinnatum juice prevented the oxytocin-induced increase in [Ca2+]i in hTERT-C3 human myometrial cells in a dose-dependent manner, achieving a ca. 80% inhibition at a 2% concentration. Comparable results were obtained with M11 human primary myometrial cells. In hTERT-C3 cells, prevention of the oxytocin-induced increase in [Ca2+]i was independent of the extracellular Ca2+ concentration and of voltage-dependent Ca2+-channels. B. pinnatum juice delayed, but did not prevent the depolarization-induced increase in [Ca2+]i in SH-SY5Y cells. Taken together, the data suggest a specific and concentration-dependent effect of B. pinnatum juice on the oxytocin signalling pathway, which seems to corroborate its use in tocolysis. Such a specific mechanism would explain the rare and minor side-effects in tocolysis with B. pinnatum as well as its high therapeutic index.
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PMID:Juice of Bryophyllum pinnatum (Lam.) inhibits oxytocin-induced increase of the intracellular calcium concentration in human myometrial cells. 2038 26