Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Oxytocin receptor (OTR) gene transcription has predominantly been thought to be regulated by estrogen. However, the continuous presence of receptors in certain brain regions after gonadectomy suggests the existence of alternate mechanisms of regulation. We have cloned and sequenced 4 kb of 5'-flanking DNA of the rat OTR gene and identified an internal segment which was absent in the initial publication of this promoter sequence. Sequence analysis of this segment, as well as of a novel upstream region, revealed the presence of a CRE as well as several other potential regulatory elements, including AP-1, AP-2, AP-3, AP-4 sites, an ERE, and a half-SRE (SRE/2). The effects of phorbol 12-myristate 13-acetate (PMA), forskolin, and NGF treatment on this promoter were tested in transfection experiments in MCF7 and SK-N-SH cells. Transcription of the full-length OTR promoter was induced by forskolin and by the phorbol ester PMA, and a synergistic (17-fold) effect was observed in MCF7 cells treated with both agents. Receptor binding studies using the OTR antagonist 125I-labeled ornithine vasotocin, and Western blot analyses of OTRs in MCF7 cells, showed that PMA and forskolin also increased the density of endogenous human oxytocin receptors. Mutational analyses of the CRE and half-SRE sites in this promoter indicated that these elements function as enhancers and support forskolin and NGF effects, respectively, on transcription. These studies have identified a novel region of the rat OTR promoter containing elements which impart cAMP and/or phorbol ester inducibility of OTR gene transcription. A potential role of the PKA and/or PKC pathways in OTR gene regulation is suggested.
...
PMID:NGF, cyclic AMP, and phorbol esters regulate oxytocin receptor gene transcription in SK-N-SH and MCF7 cells. 947 29

Oxytocin stimulates an increase in intracellular calcium in uterine myometrium by several mechanisms. Several lines of evidence indicate that the oxytocin receptor is functionally coupled to GTP-binding proteins of the G alpha q/11 class which stimulate phospholipase C activity. The IP3 generated as a result of phospholipase C activation can trigger release of calcium from intracellular stores. The finding that the oxytocin-stimulated increase in intracellular calcium in myometrial cells is greater in the presence of extracellular calcium than that in its absence indicates that oxytocin also has effects on calcium entry. This action is nifedipine-insensitive but may involve indirect stimulation of calcium entry through release-operated channels. An anti-G alpha q/11 antibody inhibits both oxytocin-stimulated GTPase activity and phospholipase C activity in myometrial membranes. The stimulation by oxytocin of phosphoinositide turnover in COS cells transfected with a plasmid expressing the oxytocin receptor is enhanced by cotransfection of G alpha q. Co-transfection of intracellular domains of the oxytocin receptor causes varying degrees of interference with oxytocin-stimulated phosphoinositide turnover. The data suggest that more than one intracellular domain is involved in oxytocin receptor/G-protein coupling. Oxytocin receptor stimulation of phospholipase C is inhibited by cAMP. This occurs in myometrial cells and in COS cells transfected with a plasmid expressing the receptor. The inhibitory mechanism involves the action of protein kinase A and is probably targeted indirectly at the G alpha q/11 /phospholipase C coupling step.
...
PMID:Molecular mechanisms regulating the effects of oxytocin on myometrial intracellular calcium. 1002 15

Oxytocin receptor (OTR) mRNA expression has previously been demonstrated in human myometrium, decidua, chorion and amnion but the effect of gestational age and the onset of labour has not been determined in these individual tissues. Spatial OTR mRNA expression was examined by in situ hybridization and ligand binding was confirmed using autoradiography with the iodinated oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]-vasotocin (125I-OTA). Tissue was collected at term (>37 weeks of gestation) or preterm (24-36 weeks of gestation) caesarean section and classified as labour (contractions every 5 min associated with cervical dilatation) or non-labour. OTR mRNA expression was measured as optical density units from autoradiographs. There was a highly significant (P<0.001) effect of tissue type on expression of OTR mRNA with expression greatest in myometrium, low in decidua and chorion and not detected in placenta. Similar results were obtained with the 125I-OTA-binding studies, indicating that the message was translated. Amnion had an apparently high level of both hybridization and 125I-OTA binding in some samples, but a lack of specificity prevented quantification of the signal in this tissue type. Term myometrium (labour and non-labour) had significantly higher (P<0.01) OTR mRNA expression than preterm myometrium, but there was no further increase in mRNA concentration associated with labour onset. In contrast, 125I-OTA binding in myometrium was already high at 33 weeks and did not increase further either later in pregnancy or with labour. In decidua there was no effect of gestational age or labour onset on OTR mRNA expression or 125I-OTA binding. In summary, OTR mRNA expression in the myometrium increased in late pregnancy whereas decidual expression was much lower and did not rise at term.
...
PMID:Oxytocin receptor expression in human term and preterm gestational tissues prior to and following the onset of labour. 1019 38

Oxytocin receptors (OTRs) are expressed in endometrial cells and oxytocin (OT) participates in endometrial functions. In cancers derived from other OT target tissues, such as breast and neural tissues, the expression of OTRs and the antiproliferative effect of OT on cancer cells has been previously observed. This study was therefore designed to search for OTR expression and the OT effect in endometrial carcinomas. To demonstrate the presence and the location of OTRs and OTR mRNA immunocytochemical, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) procedures were employed in a series of human adenocarcinomas of the endometrium. Using an anti-OTR monoclonal antibody (IF3), OTRs were demonstrated in the large majority of endometrial carcinomas (82%), with a pattern of positivity varying from diffuse to focal, according to tumour differentiation. The OTR gene was demonstrated in 78% of the cases by RT-PCR and its presence was confirmed in selected cases by ISH. Moreover, in a human endometrial carcinoma cell line (COLO 684) OTR was demonstrated by immunofluorescence and RT-PCR and it was observed that OT treatment (10(-11)-10(-7) M) significantly inhibited cell proliferation. Neither toxic effects nor apoptosis were induced by OT treatment. The addition of an inhibitor of protein kinase A (PKA) to the culture medium abolished the antiproliferative effect of OT, suggesting that cAMP via PKA could be the intracellular mediator of the OT effect, as previously observed in breast and neural tumours. In conclusion, this study presents evidence of OTR expression in human endometrial carcinomas and of an OT antiproliferative effect on human endometrial cancer cells in vitro. It is further suggested that OT and OTR may be involved in the regulation of endometrial cells, not only in physiological conditions but also in a neoplastic context.
...
PMID:Oxytocin receptors in human adenocarcinomas of the endometrium: presence and biological significance. 1069 97

Oestradiol treatment can increase uterine oxytocin receptor expression in vivo. The actions of oestrogen are usually mediated via its receptor, but it also has direct non-genomic effects in some cells. This study investigated the effect of oestradiol and the role of the oestradiol receptor in regulating endometrial oxytocin receptor expression in the bovine uterus. Explant cultures (in triplicate) from late luteal phase non-pregnant endometrium received the following treatments: control (serum-free medium), oestradiol (0. 1 and 0.01 micromol l(-1)), oestradiol (0.1 micromol l(-1)) with the oestradiol receptor antagonist ICI 182780 (0.5 micromol l(-1)), and ICI 182780 (0.5 micromol l(-1)) alone. Explants were collected 12, 24 and 48 h after the start of culture. Oxytocin receptor mRNA expression in the explants was measured by in situ hybridization and oxytocin protein concentrations were measured by autoradiography with the iodinated oxytocin receptor antagonist d(CH(2))(5) [Tyr (Me)(2) Thr(4) Tyr NH(2)(9)]-vasotocin ((125)I-labelled oxytocin receptor antagonist). Oxytocin receptor mRNA and protein expression were initially low but spontaneous upregulation occurred in the luminal epithelium between 24 and 48 h (P < 0.01). Oestradiol increased oxytocin receptor mRNA upregulation in the first 24 h (P < 0.05) but the effect on 125 I-labelled oxytocin receptor antagonist binding was not significant. ICI 182780 inhibited the oestrogenic effect but had no significant effect on oxytocin receptor mRNA expression when given alone. In conclusion, the results showed that oestradiol exerts its effect via the oestradiol receptor. Oestradiol facilitates oxytocin receptor gene transcription by increasing it more rapidly, but spontaneous upregulation of endometrial oxytocin receptor still occurs in the absence of oestradiol.
...
PMID:Oestradiol regulation of oxytocin receptor expression in cyclic bovine endometrium. 1086 41

The increase in uterine oxytocin receptor concentrations over the late luteal phase of the oestrous cycle in sheep is thought to play an important role in the regulation of the duration of the cycle by facilitating the effect of oxytocin on uterine prostaglandin release. Experiments indicated that oxytocin receptor mRNA expression in the endometrium was high at oestrus compared with at days 2, 7 and 12 of the oestrous cycle. The amount of oxytocin receptor mRNA expression in the pituitary gland did not show any significant differences during the oestrous cycle. Oxytocin receptor cDNA was obtained and characterized from ovine uterine endometrium on day 15 of the oestrous cycle, using RT-PCR techniques, to study the mechanisms underlying the resolution of oxytocin receptor expression. The cDNA sequence for the oxytocin receptor gene in sheep was found to be similar to that described previously, except for a difference of seven nucleotides. These nucleotide differences resulted in changes in four of the deduced amino acids in the oxytocin receptor sequence. The heterogeneity of the different sized oxytocin receptor transcripts in sheep is due, at least in part, to the alternative use of polyadenylation sites. Northern hybridization confirmed that the oxytocin receptor gene is expressed in ovine corpus luteum. The investigations on oxytocin receptor gene expression indicate that the patten of oxytocin receptor gene expression in sheep is not only tissue-specific, but also highly function-related. Evidence was obtained of mRNA editing in both the coding and the 3'-untranslated (3'UTR) regions of oxytocin receptor gene transcripts in ovine endometrium; this was the first demonstration of this phenomenon for oxytocin receptor mRNA. The present results indicate that the observed differences in oxytocin receptor mRNA sequences for the different oxytocin receptor populations in endometrium are due to mRNA editing. mRNA editing of oxytocin receptor transcripts may be reflected in changes in the amino acid composition of the carboxyl terminus of the receptor, which would explain the differences in the observed responses to an oxytocin challenge.
...
PMID:Regulation of oxytocin receptor gene expression in sheep: tissue specificity, multiple transcripts and mRNA editing. 1100 61

We investigated the developmental expression of vasopressin and oxytocin receptor and peptide mRNA using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization. Messenger RNAs for both vasopressin receptor subtypes V(1)a and V(2)were present in the telencephalon from embryonic day 12 to day 20. Both V(1)a and V(2)receptor mRNA increased on day 13 and then remained stable from embryonic day 13 to day 20. Messenger RNA for the vasopressin peptide was also detected in the telencephalon from day 12 to day 20, indicating that vasopressin could be synthesized within the rat cerebral cortex during rat embryonic development. Oxytocin receptor mRNA expression was also present in the telencephalon, but expression levels varied considerably from day 12 to day 20. No oxytocin mRNA expression was detected during rat telencephalon development. Temporal patterns of vasopressin receptor and vasopressin peptide mRNA expression along with oxytocin receptor mRNA suggest a temporal role for vasopressin- and oxytocin-mediated actions during rat telencephalon development.
...
PMID:Vasopressin and oxytocin receptor mRNA expression during rat telencephalon development. 1102 77

The effect of progesterone and estradiol on basal and oxytocin-stimulated prostaglandin F(2 alpha) production and on oxytocin receptor concentrations in endometrium from long term ovariectomized cows was investigated using an explant culture system. Uteri were obtained from cows at slaughter and endometrial explants were cultured in triplicate for up to 96 h in either control media, or media containing progesterone or estradiol. Basal prostaglandin F(2 alpha) production was unaffected by progesterone treatment but was stimulated by estradiol treatment in a dose dependent manner. Oxytocin receptor concentrations remained unchanged in control culture and were unaffected by treatment with estradiol while treatment with progesterone caused a dose-dependent inhibition. Responsiveness to oxytocin, in terms of increased prostaglandin F(2 alpha) production, developed "spontaneously" over the first 24 h of culture and was unaffected by treatment with progesterone or estradiol. In summary the results reveal a dose-dependent inhibition of oxytocin receptor concentration by progesterone and a dose-dependent stimulation of basal PGF(2 alpha) release by estradiol. The reason for the "spontaneous" development of responsiveness to oxytocin remains unknown but may result from the removal of tissue from the influence of an, as yet unidentified, inhibitory factor.
...
PMID:Hormone control of prostaglandin F(2 alpha) production and oxytocin receptor concentrations in bovine endometrium in explant culture. 1143 2

This study examined the expression patterns of oxytocin and steroid receptors in the bovine endometrium during the oestrous cycle and early pregnancy to elucidate their respective roles in the regulation of luteolysis and the maternal recognition of pregnancy. In Expt 1, uterine biopsies were collected from four cows throughout three oestrous cycles each, to provide daily samples. In Expt 2, uterine tissue was collected on days 12, 14, 16 and 18 of the oestrous cycle (n = 20) or early pregnancy (n = 16). Oxytocin receptor, oestrogen receptor alpha and progesterone receptor mRNAs were localized by in situ hybridization, and localization of oestrogen receptor and progesterone receptor was confirmed by immunocytochemistry. All three receptors showed time- and cell-specific expression patterns. Oestrogen receptor alpha increased in all regions at oestrus but high concentrations were also found in the luminal epithelium during the mid-luteal phase and in the deep glands throughout the oestrous cycle. Progesterone receptor expression was higher in the stroma than it was in the types of epithelial cell, and increased expression was observed at oestrus and during the early luteal phase. The cyclical upregulation of oxytocin receptors in the luminal epithelium on about day 16 was not related to preceding changes in the endometrial expression of either oestradiol alpha or progesterone receptors. During early pregnancy, oxytocin receptor expression was suppressed. Oestrogen receptor a concentrations increased in the non-pregnant cows and decreased in the pregnant cows between days 16 and 18, but these changes followed rather than preceded the upregulation of oxytocin receptors in the non-pregnant cows. It is concluded that the initial upregulation of oxytocin receptors in the luminal epithelium, which triggers luteolysis, is not associated directly with changes in expression of oestrogen receptor alpha.
...
PMID:Expression of oxytocin, oestrogen and progesterone receptors in uterine biopsy samples throughout the oestrous cycle and early pregnancy in cows. 1173 92

Oxytocin receptors (OTRs) are expressed in numerous tissues, including human normal endothelium. Here we investigated the expression and biological significance of OTRs in Kaposi's sarcoma (KS), an intensely angioproliferative disease of possible vascular origin with a prominent inflammatory component. Immunohistochemistry and in situ hybridization studies showed OTR expression in tumor cells of cutaneous classic and AIDS-related KS lesions. OTR mRNA and protein were also detected on cultured KS-IMM spindle cells by reverse transcription-PCR and immunofluorescence procedures. In these cells, OTR expression was up-regulated by the supernatants of resting CD4+ and CD8+ lymphocytes through a still unidentified factor. Functionality of OTRs was demonstrated because OT treatment of KS-IMM cells led to a significant increase in cell proliferation, coupled to the increase of intracellular calcium, but did not effect cell migration in vitro or angiogenesis in vivo. In addition, we demonstrated that CD4+ and CD8+ cells produce OT themselves, thus constituting an intralesional source of peptide. These results indicate that: (a) functioning OTRs are expressed in KS cells and modulated by the inflammatory counterpart of KS lesions; (b) via OTRs, OT stimulates KS-IMM cell proliferation and could, therefore, be considered a new possible relevant growth factor involved in KS progression; and finally (c) the evidence of OT synthesis by CD4+ and CD8+ lymphocytes strongly suggests the existence of local endocrine-immunological cross-talk in Kaposi's sarcoma.
...
PMID:Oxytocin is a growth factor for Kaposi's sarcoma cells: evidence of endocrine-immunological cross-talk. 1195 4


<< Previous 1 2 3 4 5 6 7 Next >>

---