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

The oxytocin and the vasopressin V1a, V1b and V2 receptors have recently been cloned and shown to form a sub-family within the large superfamily of G-protein-linked receptors. Renal V2 receptors mediate vasopressin-induced water reabsorption via induction of intracellular cAMP production in collecting duct cells. Most remaining actions of vasopressin on blood vessel constriction, liver glycogenolysis, platelet adhesion, adrenal angiotensin II secretion and certain brain functions are mediated via v1a-type receptors that are coupled to a Gq/11 protein. V1 receptor activation leads to stimulation of phospholipases C, D and A2 and an increase in intracellular calcium. Vasopressin stimulates pituitary corticotrophin release via a third vasopressin receptor type (V1b) which is present on corticotrophs. Oxytocin induces myometrial contraction, endometrial prostaglandin F2 alpha production, mammary gland milk ejection, renal natriuresis and specific sexual, affiliative and maternal behaviours via oxytocin receptors which are also coupled to a Gq/11 protein. Although only one oxytocin receptor type has been cloned so far, recent binding studies indicate that uterine endometrial oxytocin receptors may constitute a distinct receptor subtype. In contrast to most other membrane receptors, the expression of oxytocin receptors undergoes very rapid and physiologically relevant up-and-down-regulation. A > 100-fold up-regulation of uterine oxytocin receptors occurs during gestation and may represent the trigger for parturition. Indeed, oxytocin receptor antagonists are able to counteract preterm labour and may soon be available for clinical use. The presence of oxytocin receptors on breast cancer cells and the growth-inhibitory effects of OT suggest a potential use of oxytocin analogues for breast cancer treatment. Whereas no mutations of the oxytocin or V1a or V1b receptors have been found, over 60 different genetic mutations of the (renal) V2 receptor have been described which represent the cause for congenital nephrogenic diabetes insipidus.
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PMID:Vasopressin and oxytocin receptors. 873 52

In the present work, first we reviewed and completed our previous experiments on the antiproliferative effect of oxytocin (OT) in breast cancer cell lines. In vitro, OT 10 nM and 100 nM inhibited cell proliferation of MDA-MB231 (human breast carcinoma) and TS/A (mouse mammary carcinoma) cell lines. In vivo, OT significantly reduced the growth of TS/A mammary tumors. Both effects are mediated by specific receptors (OTR) distributed on cell surface. Second, using immunohistochemistry and RT-PCR we detected OTR and OTR mRNA in normal and pathological breast tissue. There is no correlation among OTR presence in breast carcinomas and the age of patients, tumor stage, estrogen receptor positivity, oncogene expression and proliferation rate of the same tumor. On the contrary, progesterone and OTR expression are correlated. These data confirm our previous evidence of a role of OT and OTR in normal and neoplastic breast cells.
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PMID:Oxytocin receptor within the breast: biological function and distribution. 970 81

This article focuses on the major hormones and growth factors for which a critical role in normal mammary growth has been clearly defined. Certainly other hormonal systems and growth factors could also affect breast cancer initiation and progression, but their exact contribution to normal and/or malignant breast cell growth is poorly delineated. Examples of such factors include somatostatin, mammostatin, mammary-derived growth inhibitor (MDGI), mammary-derived growth factor-1 (MDGF-1), inhibins, activins, androgens, glucocorticoids, vitamin D, thyroid hormones, ecosinoids, and oxytocin. Clearly, the hormonal regulation of breast cancer cell growth and survival is multifaceted and very complex. In particular, the effects of estrogens and anti-estrogens on breast cells may depend on their interaction with a wide variety of other pathways. In addition, these interactions may vary among individual breast tumors depending on other genetic changes in the tumor cells that have not been discussed here, such as oncogene activation and loss of tumor suppressors. A more detailed understanding of how cells circumvent a dependency on these pathways is greatly needed in order to identify new biological targets and to design novel therapies for breast cancers that are resistant to anti-estrogen therapy. Such agents could be used alone or in combination with anti-estrogens to improve response to a second course of hormonal therapy.
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PMID:The biology of breast cancer. 1036 33

Research suggests that oxytocin acts as a growth modulating agent for breast cancer cells. However, the signaling mechanisms responsible for these modulatory effects have not been fully elucidated. In the physiological setting oxytocin is known to stimulate contraction of myometrial cells in the uterus and myoepithelial cells in the breast by increasing intracellular free calcium ([Ca2+]i). The expression of oxytocin receptor mRNA in T-47D breast cancer cells, and four additional breast cancer cell lines (BT-549, MCF-7, MDA-MB- 231, ZR-75-1), was confirmed by RT-PCR analysis. Oxytocin-induced changes in [Ca2+]i in indo-1 AM loaded T-47D breast cancer cells were monitored using flow cytometric analysis. In this cell line, oxytocin (0, 1, 10, 100, and 1,000 nM) did not induce a dose-dependent increase in the mean 405 nm/485 nm emission ratio. These results indicate that oxytocin signaling in T-47D breast cancer cells does not appear to involve an increase in [Ca2+]i.
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PMID:Oxytocin does not induce a rise in intracellular free calcium in human breast cancer cells. 1046 79

Platelet-activating factor (PAF), a phospholipid mediator of inflammation, is present in breast cancer tissue and correlates with microvessel density. In the present study, we investigated the biological significance of PAF synthesized within breast cancer. In vitro, we observed the production of PAF by two estrogen-dependent (MCF7 and T-47D) and an estrogen-independent (MDA-MB231) breast cancer cell lines after stimulation with vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, tumor necrosis factor, thrombin but not with estrogen, progesterone, and oxytocin. The sensitivity to agonist stimulation and the amount of PAF synthesized as cell-associated or released varied in different cell lines, being higher in MDA-MB231 cells, which are known to be highly invasive. We further demonstrate, by reverse transcriptase-polymerase chain reaction and cytofluorimetry, that all of the breast cancer cells express the PAF receptor and respond to PAF stimulation in terms of proliferation. Moreover, in MDA-MB231 cells PAF elicited cell motility. In vivo, two structurally different PAF receptor antagonists WEB 2170 and CV 3988 significantly reduced the formation of new vessels in a tumor induced by subcutaneous implantation of MDA-MB231 cells into SCID mice. In conclusion, these results suggest that PAF, produced and released by breast cancer cells, can contribute to tumor development by enhancing cell motility and proliferation and by stimulating the angiogenic response.
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PMID:PAF produced by human breast cancer cells promotes migration and proliferation of tumor cells and neo-angiogenesis. 1107 30

Estrogen receptor beta (ERbeta) activates transcription by binding to estrogen response elements (EREs) and coactivator proteins that act as bridging proteins between the receptor and the basal transcription machinery. Although the imperfect vitellogenin B1, pS2, and oxytocin (OT) EREs each differ from the consensus vitellogenin A2 ERE sequence by a single base pair, ERbeta activates transcription of reporter plasmids containing A2, pS2, B1, and OT EREs to different extents. To explain how these differences in transactivation might occur, we have examined the interaction of ERbeta with these EREs and monitored recruitment of the coactivators amplified in breast cancer (AIB1) and transcription intermediary factor 2 (TIF2). Protease sensitivity, antibody interaction, and DNA pull-down assays demonstrated that ERbeta undergoes ERE-dependent changes in conformation resulting in differential recruitment of AIB1 and TIF2 to the DNA-bound receptor. Overexpression of TIF2 or AIB1 in transient transfection assays differentially enhanced ERbeta-mediated transcription of reporter plasmids containing the A2, pS2, B1, and OT EREs. Our studies demonstrate that individual ERE sequences induce changes in conformation of the DNA-bound receptor and influence coactivator recruitment. DNA-induced modulation of receptor conformation may contribute to the ability of ERbeta to differentially activate transcription of genes containing divergent ERE sequences.
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PMID:Estrogen response elements alter coactivator recruitment through allosteric modulation of estrogen receptor beta conformation. 1157 41

Oxytocin (OT) inhibits the proliferation of MCF7 estrogen-dependent human breast cancer cells, via specific OT receptors (OTR). Besides this effect, we report that OT modulates the expression of estrogen receptor alpha (ERalpha) in MCF7 cells, both at mRNA and protein level. Since the first 24 h of OT treatment the ERalpha mRNA levels are down-regulated; in contrast, ERalpha protein expression decreases at a later time. The reduced number of ERalpha goes in parallel to a temporary increase in the binding affinity of these receptors as well as to a significant increase in their estradiol (E2)-induced transcription activity. The increase in both binding affinity and transcriptional activity of ERalpha likely balances the reduction in the number of ERalpha binding sites, ruling out the hypothesis that part of the OT contrasting effect on E2-induced cell proliferation could depend on the reduced E2 binding to MCF7 cells and supporting the hypothesis of an exclusively direct OT-antimitogenic effect. This is the first evidence that OT modulates the expression of ERalpha receptors in human neoplastic cells.
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PMID:Oxytocin modulates estrogen receptor alpha expression and function in MCF7 human breast cancer cells. 1211 34

The endocrine system coordinates development of the mammary gland with reproductive development and the demand of the offspring for milk. Three categories of hormones are involved. The levels of the reproductive hormones, estrogen, progesterone, placental lactogen, prolactin, and oxytocin, change during reproductive development or function and act directly on the mammary gland to bring about developmental changes or coordinate milk delivery to the offspring. Metabolic hormones, whose main role is to regulate metabolic responses to nutrient intake or stress, often have direct effects on the mammary gland as well. The important hormones in this regard are growth hormone, corticosteroids, thyroid hormone, and insulin. A third category of hormones has recently been recognized, mammary hormones. It currently includes growth hormone, prolactin, PTHrP, and leptin. Because a full-term pregnancy in early life is associated with a reduction in breast carcinogenesis, an understanding of the mechanisms by which these hormones bring about secretory differentiation may offer clues to the prevention of breast cancer.
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PMID:Hormonal regulation of mammary differentiation and milk secretion. 1216 86

A 41-year-old woman with breast cancer was referred to the pain management clinic for a course of acupuncture for intense pain following a subcutaneous mastectomy and a latissimus dorsi flap reconstruction. She was treated with a standard course of acupuncture for breast pain, using paravertebral segmental points, trigger points, plus contralateral L14 on the non-lymphoedematous arm. She experienced an episode of galactorrhoea six days following the first treatment and during the second treatment. She had not previously lactated for four years. CT and MRI of the brain revealed no focal abnormality. Acupuncture has been used in to promote lactation in the Traditional Chinese literature using the 'Tianzong' acupoint SI11. This acupoint coincided with a trigger point over infraspinatus that was included in the neurophysiologically based acupuncture treatment. Quantitative analysis has shown an increase in the production of prolactin and oxytocin following acupuncture. These hormones are involved in the synthesis and release of milk from mammary glands respectively. This is the first report of galactorrhoea, in the contralateral normal breast, following acupuncture in a patient with breast cancer.
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PMID:Galactorrhoea following acupuncture. 1221 98

Novel sites of oxytocin receptor expression have recently been detected, including breast cancer cells, bone cells, myoblasts, cardiomyocytes and endothelial cells. These discoveries have greatly expanded the possible spectrum of oxytocin action beyond its classic role as an inducer of uterine contractions and milk ejection. Additional advances in the understanding of oxytocin receptor structure-function relationships, receptor trafficking and novel receptor-linked signaling cascades have made this receptor an attractive model for the study of G-protein-linked receptor function. Finally, the tocolytic efficiency of the oxytocin receptor antagonist atosiban, recently approved for clinical use in Europe, has opened new avenues for the prevention and treatment of preterm labor.
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PMID:The oxytocin receptor. 1282 28


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