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  • 1
    ISSN: 1534-4681
    Schlagwort(e): Prostate cancer ; UDP-glucuronosyltransferase ; UGT2B15 ; Androgen metabolism. UDP-glucuronosyltransferases (EC 2.4.1.17) (UGTs)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: UDP-glucuronosyltransferase 2B15 (UGT2B15) catalyzes the inactivation of dihydrotestosterone (DHT) by forming the DHT-glucuronide and is expressed in normal and hyperplastic prostate tissue. Alterations in the activity of this enzyme could be a major contributing factor to the bioavailability of androgens in target tissue such as the prostate. Methods: A polymorphism (D85 to Y85) has been identified in the UGT2B15 gene1 that results in a 50% reduction in enzyme activity. Previously, detection of the polymorphic nucleotide has required direct sequencing. We have developed and validated an allele-specific polymerase chain reaction (PCR) assay to identify the polymorphic base pair in the UGT2B15 gene. This assay was used to examine the distribution of the UGT2B15 polymorphism in a small case-control group (64 cases and 64 controls) from a prostate cancer study. Results: The results of this analysis show that prostate cancer patients were significantly more likely to be homozygous for the lower activity D85 UGT2B15 allele than control individuals (41% versus 19%, respectively, odds ratio 5 3.0 (95% confidence intervals 1.3– 6.5)). Conclusions: These results suggest that individuals who are homozygous for the lower activity allele may be at increased risk for developing prostate cancer.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1573-4919
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract We have demonstrated that glucocorticoids induce in DDT1 MF-2 cells by a glucocorticoid mediated mechanism the synthesis of a methionine-cysteine rich protein of 29 000 Mr (p29). Induction of p29 is not observed in DDT1 MF-2 GR glucocorticoid resistant variants which have only 7% of glucocorticoid receptor site per cell compared to wild type cells. Increased synthesis of p29 is specific to glucocorticoids since neither androgens, estrogens, progesterone nor the glucocorticoid antagonist dexamethasone mesylate are effective inducers. Stimulation of p29 synthesis in wild type cells is observed at 10−10 M triamcinolone acetonide, reaching a maximum at a concentration of 1 × 10−8 M. The induction of p29 is not a function of glucocorticoid arrest of DDT1 MF-2 cells since DDT1 MF-2 cells promoted to re-enter the cell cycle by 50 ng/ml platelet derived growth factor (PDGF) continue synthesis of p29. Finally, increased levels of p29 translation products are observed in cell free translation assays carried out utilizing poly A− RNA transcripts isolated from glucocorticoid treated cells. These data suggest that the glucocorticoid stimulation of p29 synthesis is a transcriptional and/or RNA processing event controlled by glucocorticoid receptor complexes.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1573-4919
    Schlagwort(e): glucocorticoid receptor ; β-adrenergic receptor regulation ; smooth muscle ; adenylate cyclase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract We have shown that glucocorticoids induce the appearance of β2-adrenergic receptors in membranes of the ductus deferens smooth muscle cell line (DDT1 MF-2). A concomitant increase in isoproterenol stimulated adenylate cyclase activity in the absence of exogenously applied GTP was observed as was a significantly increased (p 〈 0.05) sensitivity of the adenylate cyclase system to exogenously applied GTP. However, no significant difference in the maximal velocity of adenylate cyclase between control and steroid treatment was measurable in the presence of sodium fluoride. Induction of β2-adrenergic receptors in DDT1 MF-2 cells is correlated with the presence of steroid receptors (androgen and glucocorticoid) in the cells since estrogens and progesterones had no effect on receptor levels. Finally, utilizing dense amino acid labeling of cells to measure old versus newly synthesized receptor sites by a density shift method, we have documented that glucocorticoid induction of β2-adrenergic receptors involves synthesis of new receptor protein.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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