Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA polymerase activity was measured in vitro in soluble cytoplasmic and nuclear fractions of chick oviduct, after in vivo hormone stimulation. By twelve hours after a subcutaneous injection of oestradiol, cytosolic and nuclear DNA polymerase activity had increased 2 to 5 fold over control levels ane continued to increase until 24 hours after the injection. Progesterone induced a slight rise in DNA polymerase activity and dihydrotestosterone had no effect. When oestradiol + progesterone were given together, the stimulating effect of oestradiol was cancelled for approximately 14 hours, contrasting with their synergist-c effect on transcription in this system. Various quantities and various sequences of hormone administration were studied, and some of the physico chemical parameters of the enzymes were determined after the different hormone stimulations. The demonstration of a sex steriod dependent regulation of chick oviduct DNA polymerases and the opposite effects of the oestradiol + progesterone combination on replication and on transcription can represent a new approach in the study of the mechanism of action of steroid sex hormones.
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PMID:[Regulation of chick oviduct DNA polymerases by steroid hormones (author's transl)]. 100 13

Cytosols of human breast tumours have been assayed for DNA dependent DNA polymerase alpha activity. DNA polymerase alpha activity in benign tumours was found to be significantly lower than in untreated malignant tumours. Biopsy samples removed surgically before and after endocrine therapy showed reduced DNA polymerase alpha activity in 6 out of 9 patients treated with 4-hydroxyandrostenedione, and in 6 out of 7 patients treated with MPA. DNA polymerase alpha activity in malignant breast tumours was higher in oestrogen receptor negative than oestrogen receptor positive tumours.
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PMID:Analysis by DNA polymerase alpha activity of human breast tumour proliferation and the effect of endocrine therapy. 214 78

The effects of the antiprogestin RU 486 on the human endometrium were investigated. Seventeen postmenopausal women were injected with estradiol (E2) benzoate (0.625 mg/day) for 15 days. Progesterone (P) (25 mg/day) and/or RU 486 (100 or 200 mg/day) were given to groups of 2-3 women during the last 6 days of E2 benzoate treatment. Serial blood samples were drawn for the measurement of plasma E2, P, and LH and FSH. An endometrial biopsy was performed on the last day of treatment, and processed for histology or for assays of DNA polymerase alpha, E2-dehydrogenase (E2DH), and P receptor (PR). Treatment with E2 benzoate alone resulted in a marked decrease of plasma gonadotropins; in those patients who received either P, RU 486, or both, in addition to E2 benzoate, the concentrations of plasma LH and FSH were further decreased to premenopausal levels. In absence of glycerol, the affinity of RU 486 for the endometrial PR (Kd = 0.8 nM) was higher than that of P (Kd = 1.2 nM). Glycerol decreased markedly the affinity of RU 486, whereas the affinity of P for the PR was unchanged. RU 486 had negligible affinity for plasma transcortin. Either P or RU 486, but not both together, induced secretory changes in the endometrium as determined from histologic sections of tissue biopsies. Either P or RU 486 decreased DNA polymerase alpha and increased E2-DH activities in the endometrium. Unexpectedly, when P and RU 486 were given together. E2-DH activity remained at the level found in E2-treated women. In vitro cultures of proliferative endometrium treated with the synthetic progestagen R 5020 or with RU 486 also had increased E2-DH activity; RU 486 counteracted R 5020 effects. We conclude that, contrary to previous results with experimental animals, the anti-P RU 486 has some progestomimetic activity in humans under specific conditions. Paradoxically, when given together with P, RU 486 lost most of its progestomimetic activity in the endometrium and behaved as a pure antagonist.
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PMID:Endometrial and pituitary responses to the steroidal antiprogestin RU 486 in postmenopausal women. 396 88

After a single injection of oestradiol benzoate (1.5 mg/kg) to oestrogen-withdrawn chickens, there was an increase in magnum wet weight, DNA polymerase alpha activity, adenosine-3',5'-monophosphate-dependent protein-kinase activity and estrogen-receptor concentration, as measured over 36 h. Besides these intracellular proteins, the secretory proteins ovalbumin and conalbumin were also augmented, and detailed time-course studies were performed. Early induction kinetics for ovalbumin and conalbumin synthesis, which differed for each protein, were independent of the dose of oestradiol benzoate injected if it exceeded 0.1 mg/kg. After 6 h for ovalbumin and 2 h for conalbumin, the induction curves diverged according to the dose of hormone administered and in correlation with the persistence of elevated nuclear oestrogen-receptor concentrations, a result confirmed with 11 beta-methoxy-17 alpha-ethynyloestradiol (R 2858), a powerful synthetic oestrogen. When oestradiol benzoate (1 mg/kg) and progesterone (3 mg/kg) were injected simultaneously, the rate of conalbumin sythesis, during the first 6-8 h, was lower than that observed in animals injected with oestradiol benzoate alone. However at later times conalbumin synthesis was greater in animals receiving both hormones than with oestradiol alone. In contrast, the rate of ovalbumin synthesis after the combined injection was higher than that induced by either hormone alone throughout the entire experimental period. In order to study further the synergistic and antagonistic activities of these two hormones, a single injection of progesterone (3 mg/kg) was administered 6, 12 or 18 h after 1.5 mg/kg oestradiol benzoate. Progesterone administration resulted in a reduction in cytoplasmic, nuclear and total oestrogen receptor concentration for at least 6 h when compared with the values in birds treated with oestrogen alone. DNA polymerase and protein kinase activities were also reduced during this period. Subsequently, all parameters increased, and by 18-24 h after progesterone treatment, reached values higher than those observed in animals receiving oestrogen alone.
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PMID:Steroid receptors and effects of oestradiol and progesterone on chick oviduct proteins. 624 83

MPA [the active metabolite of the immuno-suppressive agent CellCept] and ribavirin markedly potentiate the anti-HBV activity of the guanine-based nucleoside analogue entecavir (ETV) against both wild-type HBV and a lamivudine-resistant variant. Ribavirin (in its 5'-monophosphate form) and MPA are inhibitors of IMP-dehydrogenase and cause depletion of intracellular dGTP pools. The active triphosphorylated form of ETV may inhibit more efficiently the priming reaction, reverse transcription and DNA-dependent DNA polymerase activity of the HBV polymerase in the presence of reduced levels of dGTP. The potential for enhanced ETV activity is supported by the observation that exogenously added deoxyguanosine reversed the potentiating effect of ribavirin and MPA. Our observations may have important implications for those (liver) transplant recipients that receive MMF as part of their immunosuppressive regimen and who, because of a de novo or a persistent infection with HBV need antiviral therapy such as ETV. Further studies will need to be conducted to determine if combining ribavirin (a compound used for the treatment of HCV infections) with ETV could have an advantage for the treatment of HBV infections, in particular in patients co-infected with HCV.
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PMID:Ribavirin and mycophenolic acid markedly potentiate the anti-hepatitis B virus activity of entecavir. 1709 96