Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown that early detection of breast cancer saves lives. Recently there has been increasing interest in nipple aspirate fluid as a potential avenue for breast cancer diagnosis. One major challenge regarding studies of nipple aspirate fluid is the ability to obtain adequate samples. Here we describe the use of nasal oxytocin in a group of volunteer women in order to increase the yield of nipple aspirate fluid.
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PMID:The use of oxytocin in nipple fluid aspiration. 1284 57

Previous studies have suggested that upstream stimulatory factors (USFs) regulate genes involved with cell cycle progression. Because of the relationship of USFs to an important oncogene in breast cancer, c-myc, we chose to determine the importance of USF to normal mammary gland development in the mouse. Expression of USF in the mammary gland throughout development demonstrated only modest changes. Mutation of the Usf2 gene was associated with reduced fertility in females, but had no effect on prepartum mammary gland development. However, lactation performance in Usf2-/- females was only half of that observed in Usf2+/+ females, and both lactose and nitrogen were decreased in milk from Usf2-/- dams. This decrease was associated with diminished mammary tissue wet weight and luminal area by d 9 of lactation and with a decreased protein-DNA ratio. This decrease was associated with reduced abundance of the eukaryotic initiation factors eIF4E and eIF4G. Blood oxytocin concentrations on d 9 postpartum were also lower in Usf2-/- mice than Usf2+/+ mice. In contrast, the mutation had no effect on blood prolactin concentrations, mammary cell proliferation or apoptosis, mammary tissue oxytocin receptors, or milk protein gene expression. The mutation had only modest effects on maternal behavior. These data support the idea that USF is important to physiological processes necessary for the establishment and maintenance of normal lactation and suggest that USF-2 may impact lactation through both systemic and mammary cell-specific mechanisms.
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PMID:Diminished milk synthesis in upstream stimulatory factor 2 null mice is associated with decreased circulating oxytocin and decreased mammary gland expression of eukaryotic initiation factors 4E and 4G. 1290 52

The widespread use of the selective serotonin reuptake inhibitors (SSRIs) has been accompanied by numerous reports describing a potential association with hyperprolactinemia. Antipsychotics are commonly known to elevate serum prolactin (PRL) through blockade of dopamine receptors in the pituitary. However, there is little awareness of the mechanisms by which SSRIs stimulate PRL release. Hyperprolactinemia may result in overt symptoms such as galactorrhea, which may be accompanied by impaired fertility. Long-term clinical sequelae include decreased bone density and the possibility of an increased risk of breast cancer. Through literature review, we explore the possible pathways involved in serotonin-induced PRL release. While the classic mechanism of antipsychotic-induced hyperprolactinemia directly involves dopamine cells in the tuberoinfundibular pathway, SSRIs may act on this system indirectly through GABAergic neurons. Alternate pathways involve serotonin stimulation of vasoactive intestinal peptide (VIP) and oxytocin (OT) release. We conclude with a comprehensive review of clinical sequelae associated with hyperprolactinemia, and the potential role of SSRIs in this phenomenon.
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PMID:From galactorrhea to osteopenia: rethinking serotonin-prolactin interactions. 1499 75

Oxytocinase has been reported to hydrolyse the peptide hormone oxytocin (OT). We have previously described changes in oxytocinase activity in human breast cancer, where a highly significant increase occurred in tumoral tissue. In the present work, we analysed oxytocinase activity in serum of rats with breast cancer induced by N-methyl-nitrosourea (NMU). We also correlated these data with the number and size of tumors and the body weight of the animals to evaluate the putative value of this activity as a biological marker of the disease. Our results confirm the involvement of OT in carcinogenesis and suggest a mayor role for oxytocinase activity in the development of breast cancer.
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PMID:Serum oxytocinase activity is related to tumor growth parameters in N-methyl nitrosourea induced rat breast cancer. 1523 94

Oxytocin (OT) plays a crucial role as a mediator of breast myoepithelial cell contraction, the process responsible for the ejection of milk during lactation, and is also involved in myoepithelial cell proliferation and postpartum mammary gland proliferation. Furthermore, although a number of breast cancer cells have oxytocin receptors (OTRs), it has been reported that OT stimulates, inhibits, or has no effect on cell proliferation. As these different effects seem to be mediated by different signaling pathways elicited by OTR stimulation, we here review the regulation of OTR signaling in different cell systems and discuss how understanding the molecular basis of receptor coupling specificity has become extremely important for understanding the role played by OTRs in regulating cell growth.
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PMID:Oxytocin receptor signaling in myoepithelial and cancer cells. 1680 2

Reduced emotional expression has been consistently related to susceptibility or fast progression of breast cancer. Breast cancer development and reduced emotional expression have both been related to rejection- and separation-related conditions. The neuropeptide oxytocin is low in response to rejection or separation. Recent results suggest that oxytocin may protect against the development of breast cancer and slow its progression. In the present study, we investigated if individual differences in emotional expressivity relate to basal or cortisol-stimulated plasma oxytocin. Healthy female subjects were treated with placebo or 35mg of cortisol orally in a double-blind within-subject study. Seventy minutes later, blood was sampled for determination of oxytocin and cortisol levels. We found an interaction between treatment condition and Emotional Expression-out scores: after cortisol treatment, oxytocin levels increased proportional to Emotion Expression-out score. These preliminary findings provide a potential mechanism for associations in the literature between emotional expressive behavior and breast cancer.
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PMID:Individual differences in emotional expressivity predict oxytocin responses to cortisol administration: relevance to breast cancer? 1726 94

Oxytocin receptor (OTR) is a membrane protein known to mediate oxytocin (OT) effects, in both normal and neoplastic cells. We report here that human osteosarcoma (U2OS, MG63, OS15 and SaOS2), breast cancer (MCF7), and primary human fibroblastic cells (HFF) all exhibit OTR not only on the cell membrane, but also in the various nuclear compartments including the nucleolus. Both an OTR-GFP fusion protein and the native OTR appear to be localized to the nucleus as detected by transfection and/or confocal immunofluorescence, respectively. Treatment with oxytocin causes internalization of OTR and the resulting vesicles accumulate in the vicinity of the nucleus and some of the perinuclear OTR enters the nucleus. Western blots indicate that OTR in the nucleus and on the plasma membrane are likely to be the same biochemical and immunological entities. It appears that OTR is first visible in the nucleoli and subsequently disperses within the nucleus into 4-20 spots while some of the OTR diffuses throughout the nucleoplasm. The behaviour and kinetics of OTR-GFP and OTR are different, indicating interference by GFP in both OTR entrance into the nucleus and subsequent relocalization of OTR within the nucleus. There are important differences among the tested cells, such as the requirement of a ligand for transfer of OTR in nuclei. A constitutive internalization of OTR was found only in osteosarcoma cells, while the nuclear localization in all other tested cells was dependent on ligand binding. The amount of OTR-positive material within and in the vicinity of the nucleus increased following a treatment with oxytocin in both constitutive and ligand-dependent type of cells. The evidence of OTR compartmentalization at the cell nucleus (either ligand-dependent or constitutive) in different cell types suggests still unknown biological functions of this protein or its ligand and adds this G-protein-coupled receptor to other heptahelical receptors displaying this atypical and unexpected nuclear localization.
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PMID:Constitutive and ligand-induced nuclear localization of oxytocin receptor. 1736 4

Two synthetic procedures for HYNIC oxytocin labeling were developed: one based on an orthogonal protection approach and the other with prelabeled (Boc)HYNIC-(Fmoc) amino acids. Both procedures were compared and applied to the preparation of several HYNIC-oxytocin derivatives where ligand position and amino acid (lysine and phenylalanine) were varied. Additionally, an oxytocin derivative labeled with HYNIC in the alpha-amino group of the Cys1 residue was also prepared. 99mTc-ethylendiaminediacetic acid (EDDA) labeling efficiencies were examined for all the derivatives, resulting in two candidates which showed affinity for the oxytocin receptor. Further biochemical experiments demonstrated that 99mTc-EDDA/HYNIC-Cys1-OT-CONH2 could be used as a potential radiopharmaceutical for breast cancer diagnosis.
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PMID:Synthesis of oxytocin HYNIC derivatives as potential diagnostic agents for breast cancer. 1766 73

A phenotypic definition of the term estrogen has become increasingly problematic due to the multiple modes of estrogen action which can now be defined by differing nuclear and membrane receptors for the classic ligand, 17beta-estradiol, and by the multiple signalling pathways that are consequently addressed. This has led to the term xenoestrogen being largely determined by whatever assay system is used for its definition. Here we describe a novel and simple matrix for a transfection system using MBA-MD231 and MCF-7 breast cancer cells as hosts. This matrix is able to vary the type of nuclear estrogen receptor used, and by varying the promoter-reporter construct between one using a classic estrogen response element (ERE) enhancer, and one using an enhancer element derived from the bovine oxytocin gene promoter binding an orphan nuclear receptor, direct classical effects can be neatly discriminated from non-classical and non-genomic actions of test substances. This assay matrix has been used to examine a selection of phytoestrogens and xenobiotics, thereby providing new information on the mechanism of action of some of these substances in breast cancer cells.
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PMID:A novel molecular assay to discriminate transcriptional effects caused by xenoestrogens. 1771 12

Oxytocin stimulates proliferation of human osteoblast-like (hOB) cells and human osteosarcoma cells (SaOS-2). In contrast, oxytocin has also been shown to inhibit proliferation of other cell lines such as breast cancer cells. The aim of the present study was to investigate the effects of different concentrations of oxytocin on cell proliferation in osteosarcoma cell lines of different stages of differentiation: SaOS-2, TE-85, and UMR-106. For this purpose cells were incubated with oxytocin (1-1000 pmol/l). Cell proliferation was measured by [(3)H]thymidine incorporation and a commercially available kit (EZ4U). Incubation with oxytocin during 24 h increased proliferation of SaOS-2 cells significantly (100 pmol/l: p<0.01). In contrast, 24 h of incubation with oxytocin decreased proliferation of TE-85 (100 pmol/l: p<0.01) and UMR-106 cells significantly (100 pmol/l: p<0.01). The effects of oxytocin in SaOS-2 and TE-85, but not in UMR-106 cells, were abolished when the cells were incubated with both oxytocin and an oxytocin antagonist (1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin). Instead incubation with the oxytocin antagonist alone decreased proliferation of UMR-106 cells significantly (p<0.001). Thus oxytocin has the capacity to both stimulate and inhibit cell proliferation of osteosarcoma cells. This effect might be dependent on the stage of differentiation of the cancer cells.
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PMID:Opposite effects of oxytocin on proliferation of osteosarcoma cell lines. 1838 94


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