UNIPROT:P01178 - FACTA Search

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)

We describe a novel neuroendocrine test which reflects a central response to activation of oestrogen receptors. This is achieved by measurement of plasma levels of oestrogen-stimulated neurophysin (ESN) following an oestrogen challenge. In normal women the ESN response to ethinyl oestradiol is dose-dependent. This response is attenuated in normal women during the first postpartum month, although it is unchanged in patients with anorexia nervosa, in spite of their similar concurrent hypo-oestrogenic state. The altered puerperal response may result from the acute oestrogen withdrawal which occurs at delivery. The time course of the altered ESN response coincides with the period of maximum risk for puerperal psychosis. The ESN response to oestrogen provides a novel neuroendocrine measure to test the relevance of changes in central oestrogen receptor responsiveness in the pathogenesis of puerperal psychosis.
...
PMID:Changes in a proposed new neuroendocrine marker of oestrogen receptor function in postpartum women. 228 86

The non-steroidal antioestrogen tamoxifen (trans-1-(4-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut- 1-ene), widely used in the treatment of breast cancer, and its oestrogenic cis-isomer rapidly inhibited contractile responses of isolated rat myometrium to supramaximal concentrations of oxytocin (1.28 X 10(-6) mol/l). Both compounds were effective at concentrations comparable with the plasma concentrations of tamoxifen reached in therapy (i.e. 5 X 10(-7) to 5 X 10(-6) mol/l). Inhibition was too rapid in onset (less than 3 min) to involve changes in RNA transcription and protein synthesis, and was not prevented or reversed by the addition of oestradiol to the bath. We conclude that the inhibition did not involve the classical oestrogen receptor pathway. Oestradiol-17 beta at concentrations above 10(-6) mol/l also inhibited the myometrium and potentiated the effects of the anti-oestrogens. Our experiments suggest that the anti-oestrogens and oestradiol act via a similar route with tamoxifen having an equilibrium affinity approximately tenfold greater than that of oestradiol.
...
PMID:Acute inhibition of rat myometrial responses to oxytocin by tamoxifen stereoisomers and oestradiol. 650 64

The mechanisms by which oestrogen modulates the biosynthetic and secretory activity of magnocellular oxytocin neurones are poorly understood. Using an antibody directed against the oestrogen receptor (ER), the distribution of ER-immunoreactive (-IR) cells in relation to the supraoptic nucleus (SON) was examined. Although no ER-IR cells were detected within the SON, a small population of immunoreactive cells separate from those in the preoptic area was identified in the perinuclear zone of the SON. Double-labelling experiments with an antibody specific for glutamic acid decarboxylase (GAD), the neuronal enzyme producing gamma aminobutyric acid (GABA), revealed that approximately 60% of perinuclear zone ER-IR cells contained GAD. A further set of immunocytochemistry experiments using an antibody raised against the beta 2 and beta 3 sub-units of the GABAA receptor revealed immunoreactivity in the SON. Double-labelling experiments demonstrated that both oxytocin-IR and non-oxytocin-IR neurones in the SON were immunoreactive for beta 2 and/or beta 3 sub-units of the GABAA receptor. These studies have identified ERs within a GABAergic neural population in the perinuclear zone of the SON and shown that magnocellular oxytocin neurones in the SON possess GABAA receptors comprised of beta 2 and/or beta 3 sub-units. In conjunction with previous evidence that the perinuclear zone GABA neurones are an important source of GABA terminals in the SON, these results provide a morphological basis for the hypothesis that perinuclear zone GABA neurones may be part of a steroid-sensitive neural circuitry transmitting oestrogen input to oxytocin neurones in the SON.
...
PMID:Immunocytochemical evidence for oestrogen receptors within GABA neurones located in the perinuclear zone of the supraoptic nucleus and GABAA receptor beta 2/beta 3 subunits on supraoptic oxytocin neurones. 802 69

This study determined whether twice-daily intrauterine injections of ovine conceptus secretory proteins (oCSP) containing type-I trophoblast interferon (25 micrograms/uterine horn) from day 11 to day 15 post-oestrus (oestrus = day 0) could alter the binding capacities of endometrial receptors for oxytocin, progesterone and oestrogen in cyclic ewes when compared with control ewes receiving serum protein (SP) injections. Injections of oCSP on days 11-15 post-oestrus decreased concentrations of oestrogen receptors (P < 0.06), oestrogen receptor mRNA (P < 0.05) and progesterone receptors (P < 0.08) in endometrium on day 16 when compared with SP-infused control ewes, which were undergoing corpus luteum regression on days 14-16. Injection of oCSP also decreased the number (P < 0.10) and affinity (P < 0.06) of oxytocin receptors. Inositol phosphate formation induced in the endometrium on day 16 by 100 nM oxytocin in vitro was highly correlated with the concentration (r > or = 0.93, P < 0.001) and Kd (r = -0.91, P < 0.01) of oxytocin receptors in SP-infused ewes, but was not as highly correlated with concentration (r < or = 0.83, P < 0.06) and Kd (r < or = 0.40, P > 0.40) of oxytocin receptors in oCSP-infused ewes. This indicates that oCSP disrupted the relationship between oxytocin receptor binding and oxytocin-induced activation of its second messenger system. These results indicate that antiluteolytic type-I trophoblast interferon may prevent oxytocin-induced luteolytic pulsatile secretion of prostaglandin F2 alpha during maternal recognition of pregnancy in sheep, by reducing the synthesis and affinity of endometrial oxytocin receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Changes in progesterone and oestrogen receptor mRNA and protein and oxytocin receptors in endometrium of ewes after intrauterine injection of ovine trophoblast interferon. 838 10

Oestrogen influences both oxytocin mRNA and peptide immunoreactivity in the preoptic area and the rat oxytocin gene contains functional oestrogen response elements. However, using combinations of immunocytochemistry and in situ hybridization for oxytocin and oestrogen receptor, we found that preoptic oxytocin neurons do not possess oestrogen receptors. This finding implies oestrogen actions on oxytocin synthesis in preoptic neurones are unlikely to be mediated directly.
...
PMID:Differential cellular localization of oestrogen receptor immunoreactivity and oxytocin mRNA and immunoreactivity in the rat preoptic area. 861 70

This study determined the effects of intrauterine injections of recombinant ovine interferon-tau; (roIFN-tau; 2 x 10(7) antiviral units/day) or control proteins (6 mg/day) from day 11 to day 14 post-oestrus = day 0) on endometrial expression of receptors fro oestrogen, progesterone and oxytocin in cyclic ewes. Plasma concentrations of progesterone were greater on day 15 in ewes receiving roIFN-tau compared with control proteins (P < 0.02, treatment x day). Ewes injected with roIFN-tau had lower endometrial levels or oestrogen receptor mRNA (P > 0.10) and protein (P < 0.01) on day 15 compared with ewes receiving control proteins. In situ hybridization analysis indicated that oestrogen receptor mRNA was more abundant in the luminal and glandular epithelium of control ewes compared with roIFN-tau-treated ewes. Immunoreactive oestrogen receptor was also present in the luminal and glandular epithelium of control, but not roIFN-tau-treated ewes. Endometrial levels of progesterone receptor mRNA and protein were not different (P > 0.10) between control and roIFN-tau-treated ewes. In situ hybridization analyses indicated that progesterone receptor mRNA abundance was low in endometrial epithelium and stroma of both control and roIFN-tau-injected ewes. Immunoreactive progesterone receptors were present in the endometrial stroma and epithelium of control ewes, but confined to the stroma of roIFN-tau-treated ewes. Oxytocin receptor density was lower (P < 0.01) in the endometrium of ewes injected with roIFN-tau than control proteins; however, oxytocin receptor affinity was not affected (P > 0.10) by treatment. Concentrations of 13,14-dihydro-15-ketoprostaglandin F2a (PGFM) were not increased by exogenous oxytocin administration in control and roIFN-tau-treated ewes on days 10 or 12 post-oestrus. However, on day 14, control ewes responded to oxytocin with increased plasma concentrations of PGFM, whereas ewes receiving roIFN-tau remained unresponsive to oxytocin. These results indicate that the an tiluteolytic effects of IFN-tau are to prevent increases in endometrial oestrogen receptor MRNA and protein and oxytocin receptor density which abrogates uterine release of prostaglandin F2a during maternal recognition of pregnancy. IFN-tau may inhibit the synthesis of oestrogen receptor mRNA by a transcriptional or post-transcriptional regulatory mechanism to suppress oxytocin receptor formation during early pregnancy in ewes.
...
PMID:Intrauterine injection of ovine interferon-tau alters oestrogen receptor and oxytocin receptor expression in the endometrium of cyclic ewes. 880 Jun 45

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.
...
PMID:The effect of pregnancy on the expression of uterine oxytocin, oestrogen and progesterone receptors during early pregnancy in the cow. 985 73

1. Intracellular current clamp recordings were performed from identified oxytocin (OT) neurones in acute hypothalamic slices taken from lactating Wistar rats at early (5th day: LD-5) and late (21st day: LD-21) lactation. 2. The basic electrophysiological properties of LD-21 OT neurones differed from those of LD-5 OT neurones: their resting membrane potential was more depolarised (-51.5 versus -54.9 mV); their action potential duration was longer (1.6 versus 1.2 ms); their hyperpolarising after-potential (HAP) following single spikes and after-hyperpolarisation (AHP) following a burst of action potentials had smaller amplitudes (-46 and -67 %, respectively); and they lacked spike frequency adaptation during a burst. 3. In LD-21 neurones bath application of 17beta-oestradiol (10-7 M, 6-14 min) reversibly restored all these properties to values observed in LD-5 cells. This treatment had no effect on LD-5 neurones. 4. LD-21 neurones were less sensitive to kainate than LD-5 neurones. 17beta-Oestradiol significantly potentiated the kainate-induced response in LD-21, but not in LD-5 neurones. 5. The effects of 17beta-oestradiol were presumably mediated through a non-genomic mechanism since they occurred within a few minutes of administration, and disappeared within 30-40 min of washout. They were not inhibited by tamoxifen, an antagonist of the nuclear oestrogen receptor ER-alpha. Lastly, cholesterol, a non-active lipophilic molecule, had no effect. 6. Our observations demonstrate that, in the absence of 17beta-oestradiol, the basic electrical properties and sensitivity to kainate of OT neurones become altered between early and late lactation. However, the rise in circulating levels of oestrogens during the late phase of lactation may contribute to maintain OT neurone reactivity as long as suckling continues.
...
PMID:17-Oestradiol modulates in vitro electrical properties and responses to kainate of oxytocin neurones in lactating rats. 1076 12

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

In vivo there appears to be a marked association between oestrogen levels and the expression of the oxytocin (OT) gene in most tissues. Transfection and DNA-protein binding experiments using high levels of either oestrogen receptor (ER)alpha or ERbeta imply a direct interaction of these transcription factors with the multiple hormone response element (HRE) at approximately -160 from the transcription start site of the OT gene in most species. In an extensive set of experiments, we show, using both transfection and protein-DNA binding, that low to moderate amounts of either oestrogen receptor, while being able to interact directly with a classic oestrogen response element (ERE) fail to interact with the human OT -160 HRE. Instead, this element, similar to its bovine counterpart, has a high affinity for the orphan receptors steroidogenic factor 1 and chicken ovalbumin upstream promoter transcription factor. Second, the human and bovine OT promoter can be made artificially responsive towards oestrogen in a cotransfection system over-expressing ERalpha or ERbeta, but not in cells expressing natural levels of these steroid receptors. Interestingly, nuclear extracts from both ERalpha-positive MCF7 cells and ERalpha-negative MDA-MB231 cells both contain a transcription factor which binds specifically to both the hOT-HRE element and to a classic ERE, and which has orphan receptor-like binding properties rather than those of an oestrogen receptor. Together, these and other results suggest that oestrogen action in vivo on the OT gene in all species is more likely to involve a DNA-independent mechanism than classic direct interactions with dimeric oestrogen receptors.
...
PMID:The affinity and activity of the multiple hormone response element in the proximal promoter of the human oxytocin gene. 1204 22

1 2 3 Next >>