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

The bovine oxytocin gene is massively up-regulated during the early development of the corpus luteum. Oxytocin transcription is induced in a highly synchronous fashion in the granulosa cells of the dominant follicle at the time of ovulation. The possibility to isolate large numbers of differentiating granulosa-luteal cells from exactly defined stages of development allows the investigation of the factors controlling oxytocin expression in vivo by molecular and cell biology methods. Using primary cultures of bovine granulosa cells the synergistic activation of oxytocin transcription by the cAMP pathway and stimulation of IGF-I or insulin receptors could be established. Analysis of transcription factors isolated from the nuclei of bovine granulosa cells and corpus luteum led to the identification of the tissue-specific orphan receptor SF-1 binding to the promoter of the actively transcribed oxytocin gene. The luteinizing bovine granulosa cells provide the only easily accessible experimental system established so far in which the endogenous oxytocin gene is expressed. Although the link between increased cAMP level and receptor tyrosine kinase activation on the one hand and the induction of oxytocin transcription on the other has not been established yet, these experiments constitute one of the few direct approaches to investigate the complexity of events that regulate oxytocin expression in vivo.
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PMID:Regulation of oxytocin expression in the bovine corpus luteum. Orphan receptors and the oxytocin promoter. 871 54

A physiological role for oxytocin in stimulating uterine contractions during labour is well accepted, but has not yet been well defined. Oxytocin activates phospholipase C to produce inositol 1,4,5-trisphosphate, which releases Ca2+ from intracellular stores. There is considerable evidence that G-proteins are involved in this signalling pathway. The objectives of the present study were to determine the mechanisms of action of oxytocin in human myometrium. We have measured the effect of oxytocin on the formation of inositol phosphates (InsPs) in cultured human myometrial cells labelled with [3H] inositol and on changes in intracellular free Ca2+ concentration ([Ca2+i]) in single cells using a dynamic calcium imaging system. Pertussis toxin was used to obtain information on the G-proteins involved. Oxytocin induced InsPs formation and [Ca2+i] mobilisation in a concentration-dependent manner in human myometrial cells. Our data suggest that two distinct types of G-proteins are involved in the oxytocin response: one most probably a member of the Gq family (pertussis toxin-resistant) and another of the Gi family (pertussis toxin-sensitive). Using Western blotting, we have found that the pertussis toxin-resistant G-proteins alpha(q), alpha(11) and alpha(2), and pertussis toxin-sensitive alpha(i1), alpha(i2), and alpha(i3) are expressed in these cells. We have also detected the phospholipase C isoforms beta(1), beta(2) and beta(3) which are regulated by G-proteins, and phospholipase C isoforms gamma(1) and gamma(2), regulated by receptor tyrosine kinase pathways. However, oxytocin does not stimulate tyrosine phosphorylation in myometrial cells. Extracellular Ca2+ does not play a direct role in the activation of phospholipase C by oxytocin. Protein kinase C causes a strong inhibitory feedback on the oxytocin pathway: protein kinase C activators abolish the response to oxytocin while inhibitors potentiate it. Oxytocin responsiveness is upregulated by incubating the cells in the presence of oestradiol. This effect is reversed by the anti-oestrogen tamoxifen. Oestrogens exert their effects on the oxytocin pathway at a postreceptor level, possibly by affecting the expression of G-proteins and/or phospholipase C isoforms.
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PMID:Oxytocin signalling in human myometrium. 871 98

A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube formation of human umbilical endothelial cells (HUVEC). Its maximum potency at 100muM was stronger than that of vascular endothelial growth factor (VEGF), a positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl-C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT-A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also suggested the angiogenic potency of 2Cl-C.OXT-A.
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PMID:A novel nucleic acid analogue shows strong angiogenic activity. 2069 60