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)

In an attempt to delineate the nature of the immunoreactive neurophysins in oat cell carcinomas of the lung with ectopic vasopressin production, tumor neurophysins were characterized by gel filtration and by electrophoresis. In all of the five tumor tissues, activities of both vasopressin and nicotine-stimulated neurophysin (NSN) determined by radioimmunoassay were demonstrated. A small amount of oxytocin as well as estrogen-stimulated neurophysin was detected in three of the tissues. When tissue extract was subjected to Sephadex G-50 gel filtration in 0.2 N acetic acid, the major portion of immunoreactive NSN emerged in the fractions corresponding to the molecular size of 10,000. The migration pattern of NSN in these fractions on electrophoresis was qualitatively the same as that of NSN extracted from human posterior pituitary glands. In addition to this major neurophysin, immunoreactive NSN with the molecular size of 20,000 was consistently demonstrated in three tumor extracts. This high molecular weight form of neurophysin represented 6.5--8.7% of total NSN immunoactivities in each tumor extract and its elution profile was not changed when analyzed under denaturating conditions in 6 M guanidine hydrochloride. On electrophoresis, it migrated near the gamma globulin region; however, the peak was broad suggesting that it consists of more than two different molecular populations. A substantial portion of the high molecular weight NSN appears to be a glycoprotein judging from its binding to concanavalin A. When the high molecular weight from of neurophysin was incubated with trypsin, essentially all of the activities were converted into NSN with the molecular size of 10,000. Moreover, an equimolar amount of vasopressin was liberated after the treatment, the elution pattern of which closely resembled that of synthetic arginine vasopressin. When a lower concentration of trypsin was used, some of the 20,000-dalton neurophysin exhibited activities of both NSN and vasopressin. Since the antivasopressin serum used in this study appeared to be directed toward the ring portion side of vasopressin, these results suggest that this 20,000-dalton neurophysin is, in all probability, a common precursor to vasopressin and neurophysin, and that vasopressin may be located in the middle of the precursor molecule.
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PMID:Nature of the immunoreactive neurophysins in ectopic vasopressin-producing oat cell carcinomas of the lung. Demonstration of a putative common precursor to vasopressin and neurophysin. 626 3

At diagnosis, 65% of 103 patients with small cell carcinoma of the lung were found to have elevated plasma concentrations of vasopressin-associated human neurophysin (VP-HNP), oxytocin-associated human neurophysin (OT-HNP), or both, which were thought to be related to tumor secretion of these proteins. The remainder of patients were designated as nonsecretors (24%) or possible secretors (11%), depending upon plasma concentration of the neurophysins prior to therapy. There was a significantly higher percentage of secretors among patients with extensive disease (82%) than among those with limited disease (40%) (P = 0.001). However, within each stage group, there was no correlation between secretory status and response to therapy, survival, or histologic subtype. In addition, patients who initially were nonsecretors or possible secretors maintained this status throughout the course of disease remission and subsequent relapse. These findings suggest the possibility of biochemical differences between tumors which present as limited disease and those which present as extensive disease. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was infrequent in limited disease but was present in 33% of patients with extensive disease. SIADH was not seen without VP-HNP elevation; however, with extensive disease, 49% of patients with elevated VP-HNP had SIADH. In contrast, elevated plasma concentrations of the neurophysins were seen in only 19.6% of 56 patients with non-small cell carcinoma of the lung. The levels were in general lower than those in patients with small cell carcinoma and were seen at approximately equal frequencies in each major cellular subtype.
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PMID:Human neurophysins in carcinoma of the lung: relation to histology, disease stage, response rate, survival, and syndrome of inappropriate antidiuretic hormone secretion. 631 32

mRNA from membrane-bound polysomes of bovine hypothalamus was translated in an mRNA-dependent cell-free system from reticulocyte lysate or wheat germ. The translation products were identified by immunoprecipitation with antibodies to either neurophysin II or arginine vasopressin followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. An immunoreactive polypeptide was obtained with an apparent Mr of 21,000. Sequential immunoprecipitation studies indicated that the Mr 21,000 product is a common precursor to neurophysin II and arginine vasopressin. The specificity of the immunoprecipitation was demonstrated by competition with excess amounts of unlabeled neurophysin II or arginine vasopressin; little or no competition was observed with unlabeled neurophysin II or arginine vasopressin; little or no competition was observed with unlabeled neurophysin I or oxytocin. Processing experiments with microsomal membranes from dog pancreas or tunicamycin-treated ascites tumor cells showed that the Mr 21,000 polypeptide is the prepro form. It was converted to a pro form with Mr 19,000 suggesting a pre sequence of approximately 15 amino acids. The Mr 19,000 polypeptide was coreglycosylated to an apparent Mr of 23,000, indicating that the neurophysin II-arginine vasopressin precursor is a glycopolypeptide.
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PMID:Immunological identification of a common precursor to arginine vasopressin and neurophysin II synthesized by in vitro translation of bovine hypothalamic mRNA. 694 Jan 45

Immunohistochemical analysis for products of vasopressin and oxytocin gene expression was performed on acetone-fixed tissues from 19 breast cancers representing a variety of tumor sub-types. Studies employed the avidin-biotin complex (ABC) immunohistochemical procedure and utilized rabbit polyclonal antibodies to arginine vasopressin (VP), provasopressin (ProVP), vasopressin-associated human glycopeptide (VAG), oxytocin (OT), oxytocin-associated human neurophysin (OT-HNP), and a mouse monoclonal antibody to vasopressin-associated human neurophysin (VP-HNP). Western Blot analysis was performed on protein extracts of fresh-frozen tissues from 12 additional breast tumors. While VP gene related proteins were not detected in normal breast tissue, immunohistochemistry revealed the presence of VP, ProVP, and VAG in all neoplastic cells for all of the tumor tissues examined. Vasopressin-associated human neurophysin was evident in only one of 19 acetone-fixed tumor preparations. However, Western blot analysis for all 12 fresh-frozen tumor samples showed the presence of two proteins, 42,000 and 20,000 daltons, that were immunoreactive with antibodies to VP, VP-HNP, and VAG. Oxytocin and OT-HNP, by immunohistochemistry, were found to be common to cells of normal breast tissues. For tumors, positive staining for OT was observed in 8 of 18 tumors, while OT-HNP was not detected in any of the tumors examined. These findings indicate that VP gene expression is a selective feature of all breast cancers, and that products of this expression might therefore be useful as markers for early detection of this disease and as possible targets for immunotherapy.
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PMID:Vasopressin gene related products are markers of human breast cancer. 757 87

Normal and neoplastic growth of epithelial cells depends on mutual interactions between epithelial and stromal cells. As a tool for the study of the underlying molecular mechanisms, we have developed temperature-sensitive, nontransformed cell lines derived from rat uterine epithelium and stroma by transfecting primary cultures with a temperature-sensitive mutant of the SV40 large T antigen. The epithelial and stromal cell lines obtained shared relevant morphological characteristics with the primary cells from which they were derived. Immunocytochemical analysis showed that the epithelial cell lines expressed the intermediate filament cytokeratin, whereas the stromal lines expressed the intermediate filament vimentin. Alkaline phosphatase activity was present in all cell lines examined. All cell lines were anchorage dependent and did not form foci. One epithelial cell line expressed oxytocin mRNA, a gene product recently shown to be highly expressed in vivo in the uterine epithelium at term. If grown on Matrigel, this cell line formed domelike structures, a further characteristic of its differentiated phenotype. In an attempt to reconstitute an endometrium in vitro, epithelial cells were seeded on top of a layer of stromal cells. Paraffin cross sections showed that this in vitro system consisted of a bilayer structure. Four to five cuboidal epithelial cells were typically anchored atop one stromal cell, forming an endometriumlike tissue. The present in vitro system should provide a useful model for further studies on endometrial functions and epithelial/stromal cell interactions at a molecular level.
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PMID:Characterization and co-culture of novel nontransformed cell lines derived from rat endometrial epithelium and stroma. 773 65

Targeted tumorigenesis, using the POMC gene promoter ligated to the simian virus 40 large T antigen, generated transgenic mice with massive tumors of the intermediate lobe (IL) of the pituitary. Inoculation of nude mice with the IL tumor cells resulted in very large secondary tumors. As the IL from several species produces a potent PRL-releasing factor (PRF), it was of interest to determine whether IL tumors from these mice also contain PRF. The objectives were to 1) measure serum PRL levels in mice with IL tumors, 2) determine whether these tumors contain PRF and examine its chromatographic properties, and 3) analyze whether this PRF is related to POMC, its derivatives, or other PRL secretagogues. Serum PRL levels were 5- to 6-fold higher in transgenic than in control mice. Primary and secondary IL tumors were acid extracted and successively fractionated using Sephadex G-100 gel filtration and reverse phase and gel permeation HPLC. PRF activity was determined using short term incubation of tissue extracts or column fractions with GH3 cells. Crude tumor extracts exhibited a strong and dose-dependent PRF activity. Upon chromatography, the PRF activity from either primary or secondary tumors resolved into two classes of compounds: a big PRF with an estimated mol wt of 70-80 kilodaltons and two small, very hydrophobic peptides. The elution profiles of the three PRFs differed from those of beta-endorphin, alpha MSH, beta MSH, ACTH, TRH, oxytocin, angiotensin II, vasoactive intestinal polypeptide, or corticotropin-like intermediate peptide. In summary, we have identified an animal model with IL tumors that has hyperprolactinemia and overproduces PRF. Two classes of PRFs, big and small, were resolved which differ from POMC derivatives and known regulators of PRL release. These data suggest that PRF is produced by melanotrophs, but is not a product of the POMC gene. The IL tumors should provide an excellent source for the purification and structural elucidation of PRFs.
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PMID:Identification of two classes of prolactin-releasing factors in intermediate lobe tumors from transgenic mice. 778 36

Bromocriptine, a dopaminergic agonist, inhibited the growth of human small cell lung cancer (SCLC) implanted as tumor xenografts in athymic nude mice; the effect was dose dependent. In mice bearing a SCLC with ectopic vasopressin production, plasma levels of human vasopressin-associated neurophysin decreased concomitantly. Electron microscopy of tumor tissues revealed marked degenerative changes, including pyknosis, densely aggregated chromatin masses, and vacuolization of cytoplasm after bromocriptine treatment. When a SCLC cell line, NCI-H69, was grown in semisolid medium, bromocriptine inhibited its clonal growth in a dose-related manner. Coincubation with dopamine D2 receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D2 receptor ligand, [125I]iodosulpride, showed high affinity binding sites on the membranes of SCLC cells. These results indicate that SCLC cells are enriched with dopamine D2 receptors, which may mediate the growth-inhibitory effect of bromocriptine on SCLC. Dopaminergic agonists may be useful in the medical treatment of SCLC.
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PMID:Inhibition of growth of human small cell lung cancer by bromocriptine. 801 64

Oxytocin (OT) and arginine vasopressin (AVP) have been reported to release PRL both in vivo and in vitro. The objectives of this study were 1) to compare the potencies of the PRL-releasing activities of OT and TRH using cultured anterior pituitary (AP) cells, and 2) to assess the PRL-releasing activity of naturally occurring neurohypophysial hormones and selected analogs. AP cells were incubated with peptides for 15 min, and medium PRL concentrations were determined by enzyme-linked immunosorbent assay. OT at 25, 100, and 400 nM increased PRL release by 110%, 175%, and 270%, respectively; higher concentrations (1600 and 6400 nM) did not cause a further increase in PRL release. TRH was 5-10 times more potent than OT on a molar basis. GH3 cells, a somatommamotroph tumor cell line, did not respond to OT and related compounds, but showed a similar responsiveness to TRH as AP cells. Twelve neurohypophysial peptides and selected analogs were incubated with AP cells, and their relative PRL-releasing activities were compared. OT and arginine vasotocin (AVT) showed the highest PRL-releasing activity. T4-G7-oxytocin, mesotocin, isotocin, lysine vasotocin, and AVP showed a moderate PRL-releasing activity, whereas, lysine vasopressin, desmopressin, tocinoic acid, pressinoic acid, and oxytocin free acid showed very low or no PRL-releasing activity. Coincubation of OT, AVT, or AVP with a specific OT receptor antagonist abolished their PRL-releasing activity. We conclude that 1) OT and related peptides are capable of stimulating PRL release in vitro, but their potencies are significantly lower than that of TRH; 2) unlike primary AP cells, GH3 cells are unresponsive to OT and related peptides; 3) AVT and AVP probably stimulate PRL release by acting via an OT receptor; and 4) the amino acid residues in positions 3 and 8 in the peptide chain and an amidated C-terminus are critical for the PRL-releasing activity of the neurohypophysial peptides.
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PMID:Prolactin-releasing activity of neurohypophysial hormones: structure-function relationship. 827 25

Production by small-cell carcinoma (SCCL) of neurophysins (HNPs) and neurophysin-related cell-surface antigen (NRSA) was examined for two cell lines, for mouse xenografts, and for a resected human tumor, using polyclonal and monoclonal antibodies to vasopressin-associated human neurophysin (VP-HNP) and polyclonal antibodies to vasopressin (VP). The nature of the mRNA responsible for giving rise to these neurophysin-related products was investigated by performing Northern analysis on preparations of poly A+RNA and cDNA probes complimentary to portions of the exon A, exon B, and exon C regions of the human VP gene. SDS-electrophoresis and Western analysis revealed two prominent proteins of 42,000 and 20,000 Da in acid extracts from all SCCL sources when the monoclonal anti-HNP or one of the two polyclonal anti-HNP preparations were used. These antibodies also disclosed the presence of a minor component of 10,000 Da. A second polyclonal anti-HNP preparation reacted with one prominent protein of 30,000 Da and, for one cell line and mouse xenografts, another protein of 32,000 Da. Both of two anti-VP preparations reacted with proteins of 42,000, 30,000, 25,000, and 20,000 Da in extracts from all SCCL source material. The immunoreactive proteins of 42,000, 30,000, and 20,000 Da were all components of a membrane fraction from SCCL cells and tissues. In Northern analysis, a single RNA of about 900 bases hybridized with exon A and exon B probes, but not with the cDNA probe complimentary to exon C of the VP gene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasopressin mRNA and neurophysin-related cell-surface antigen (NRSA) in small-cell carcinoma. 838 89

The effects of oxytocin (OT) and the OT-analogue F314 were investigated an xenografts of mouse mammary and colon carcinomas (TS/A and C26 tumors) and of rat mammary carcinoma (D-R3230AC). In all cases, proliferation was previously assessed by cell counting in cultured cell lines, whereas tumor growth was checked by serial measures of tumor volume and by evaluation of tumor weight at the end of the experiment. Both cell proliferation and tumor growth were inhibited by OT and F314. These data support previous observations on the inhibitory effect of OT and F314 on the growth of MCF7, T47D and MDA-MB231 human breast cancer cell lines and open new prospects for testing the effect of this hypothalamic hormone and its analogues on the control of breast carcinoma growth.
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PMID:Oxytocin and oxytocin-analogue F314 inhibit cell proliferation and tumor growth of rat and mouse mammary carcinomas. 864 55


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