Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is an extensive background on the androgen responsiveness of the mouse kidney which can be demonstrated histologically by hypertrophy of the Bowman's capsule and the proximal convoluted tubule. Although androgens increase many renal proteins, beta-glucuronidase and ODC are distinguished by exquisite genetic regulation of the magnitude of the response induced by testosterone. Both the qualitative and quantitative expression of the genes for these enzymes are strain specific, and are dependent upon regulatory alleles. Ornithine decarboxylase is of particular interest since the response of this enzyme is rapid compared to that of beta-glucuronidase. Recent studies using a newly developed androgen receptor assay have demonstrated that the duration of retention of the androgen receptor complex in the nucleus correlates with the magnitude of the androgenic response. Progestins can mimic, inhibit, or potentiate the action of androgens. These responses have been termed the androgenic, antiandrogenic and synandrogenic actions of progestins, respectively. The androgenic and antiandrogenic action of this class of steroids are manifest on many tissues and on many endpoints within a given organ. These effects are believed to involve an early step(s) of androgen action which is common to all sensitive tissues. Results to date suggests that this early step involves the androgen receptor. By contrast, the synandrogenic action of progestins is limited in that it is not observed on all tissues, and not even on all endpoints within a single organ. In the mouse kidney, the synandrogenic actions of progestins have been most extensively studied on beta-glucuronidase. With this enzyme this unusual response to progestins can be demonstrated only in mice which carry the Gus-ra allele. This observation suggests that the potentiating action of progestins on beta-glucuronidase is manifest directly on the Gus gene complex. It is not certain at this time whether a similar mechanism is involved in the potentiation of androgen action on other organs such as the prostate. The androgenic action of progestins is believed to be similar to that of other androgens. Androgenic progestins such as MPA bind to the androgen receptors and translocate them to nuclei. This is followed by a dose dependent increase of proteins similar to what is observed after testosterone administration. In addition, the regulatory genes which modulate androgen action have the same effect on the androgenic effect of progestins. The fact that the potency of progestins such as MPA is less than that of testosterone is believed to relate in part to their lower affinity for the androgen receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Progestins can mimic, inhibit and potentiate the actions of androgens. 637 45

The role of ornithine decarboxylase (ODC) and polyamines in kidney hypertrophy is controversial. Since part of this controversy could be related to differences in the model system used by the different authors, we studied the changes in renal ODC and polyamines in six different models of kidney hypertrophy in mice, including compensatory renal hypertrophy produced by unilateral nephrectomy, experimental diabetes, potassium depletion and treatment with hormones such as testosterone, thyroxine and fluorocortisone. Only in the case of renal hypertrophy produced by testosterone administration was there a significant increase in ODC activity and putrescine content in the kidneys. However, the concomitant treatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, as a 2% solution in the drinking water completely abolished the increase of renal ODC, but the kidney weights increased and other androgenic effects, such as the induction of renal beta-glucuronidase, were not affected. Moreover, DFMO-treatment did not prevent the kidney enlargement produced in other types of hypertrophy, even in the cases associated with hyperplasia. The present results support the premise that, at least in mice, the increase in ODC activity and polyamine biosynthesis is not required for kidney growth, and also that in most cases renal enlargement is not accompanied by any increase in the polyamine content.
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PMID:An evaluation of the role of polyamines in different models of kidney hypertrophy in mice. 747 58

Potassium deficiency produced different effects in the kidney of male or female mice. While in female, potassium deficiency caused a marked renal hypertrophy with no significant changes in testosterone-regulated enzymes, such as ornithine decarboxylase and beta-glucuronidase, in the male the same treatment provoked a marked fall of these enzymes owing to a dramatic decrease in plasma testosterone. Potassium replenishment restored plasma testosterone and renal enzymatic activities. These results show for the first time, that potassium modulates circulating testosterone and suggest that this cation could exert an important regulatory role in controlling androgen actions.
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PMID:Potassium regulates plasma testosterone and renal ornithine decarboxylase in mice. 822 66

The mouse kidney presents marked sexual dimorphism, manifested not only in renal size but also in the subcellular structure and enzyme activity. Ornithine decarboxylase (ODC), a key enzyme in the biosynthetic pathway of polyamines, is induced in the kidney by androgens, and its activity is higher in the kidney of male mice. The renal differences between male and female mice are not manifested during the first weeks of life and start to be expressed after weaning, simultaneously with the increase in plasma testosterone concentration. Treatment of newborn mice before postnatal day 21 with a single dose of testosterone propionate (TP, 200 microg/animal) did not increase renal ODC activity or renal size. From day 21 the same treatment elicited significant increases in renal ODC, especially in females where the basal activity of control animals was much lower than in males. The repeated injection of TP during the first 10 days of life (200 microg/animal, days 1, 4, 7 and 10) promoted an early increase in renal ODC activity but abolished the physiological rise observed in male mice at puberty and adulthood. This treatment dramatically reduced the secretion of the sexual hormones, testosterone, estradiol and progesterone, by the gonads, and diminished renal size as well as ODC and beta-glucuronidase activities in male mice. Stanozolol produced effects similar to those of TP, while the nonsteroidal antiandrogen, flutamide, did not apparently affect the normal development of the male or female kidney. The results indicate that: (a) kidney sexual dimorphism is not congenital; (b) neonatal androgens are not required to induce the sexual dimorphism of the mouse kidney; (c) the neonatal kidney is unresponsive to testosterone; (d) the premature and repeated exposure to supraphysiological levels of testosterone may accelerate the ontogeny of renal ODC but can abolish later testosterone secretion and hence alter the sexual characteristics of the male kidney, and (e) the postnatal treatment with androgens does not affect the response of the adult kidney to exogenous androgens. One can conclude that the postnatal manipulation of androgens may accelerate the development of the mechanisms of androgen responsiveness in some tissues but it may alter neural structures, probably the GnRH pulse generator, that control testosterone secretion.
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PMID:Postnatal exposure to androgens alters renal ornithine decarboxylase ontogeny and abolishes renal sexual dimorphism in mice. 1039 91

Polyamines are small polycations essential for cell growth. Ornithine decarboxylase (ODC), the first enzyme of the polyamine synthesis pathway, is one of the most regulated enzymes of eukaryotes. In the present report, the transcriptional regulation of the gene encoding ODC from the dimorphic fungus Yarrowia lipolytica (YlODC) was analyzed. To this end we made a transcriptional fusion of its promoter with the ORF of the beta-glucuronidase gene from Escherichia coli, and analyzed the effect of polyamines and the dimorphic transition on the rate of transcription. The results obtained show that there exists a weak but reproducible transcriptional regulation of YlODC under the analyzed conditions. Our data suggest that gene transcription is down-regulated by putrescine, and stimulated by spermidine. It is suggested that the simultaneous operation of transcriptional and post-translational regulatory mechanisms endows the cell with a more efficient mechanism to control the physiological processes that depend on polyamines.
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PMID:Analysis of the transcriptional regulation of YlODC gene from the dimorphic fungus Yarrowia lipolytica. 1859 80

While polyamines (PAs) have been suggested to protect cells against Reactive Oxygen Species (ROS), their catabolism is known to generate ROS. We compared the activities of several enzymes and cellular metabolites involved in the ROS scavenging pathways in two isogenic cell lines of poplar (Populus nigraxmaximowiczii) differing in their PA contents. Whereas the control cell line was transformed with beta-glucuronidase (GUS), the other, called HP (High Putrescine), was transformed with a mouse ornithine decarboxylase (mODC) gene. The expression of mODC resulted in several-fold increased production of putrescine as well its enhanced catabolism. The two cell lines followed a similar trend of growth over the seven-day culture cycle, but the HP cells had elevated levels of soluble proteins. Accumulation of H(2)O(2) was higher in the HP cells than the control cells, and so were the activities of glutathione reductase and monodehydroascorbate reductase; the activity of ascorbate peroxidase was lower in the former. The contents of reduced glutathione and glutamate were significantly lower in the HP cells but proline was higher on some days of analysis. There was a small difference in mitochondrial activity between the two cell lines, and the HP cells showed increased membrane damage. In the HP cells, increased accumulation of Ca was concomitant with lower accumulation of K. We conclude that, while increased putrescine accumulation may have a protective role against ROS in plants, enhanced turnover of putrescine actually can make them vulnerable to increased oxidative damage.
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PMID:Putrescine overproduction negatively impacts the oxidative state of poplar cells in culture. 1913 66

The role of dietary factors in prevention of chemically-induced cancer was reviewed on two models: i) the role of high fiber diets in prevention of colon cancer and ii) the role of high fat diets in prevention of mammary gland cancer, i) Experiments in colon cancer showed that 20% cellulose content decreased tumor incidence caused by 1,2-dimethylhydrazine (DMH) to 33% compared with 92% of tumors developed in animals fed a fiber-free diet. The tumor-preventive effect of a cellulose diet was accompanied by increased enzyme concentrations, such as ornithine decarboxylase, thymidine kinase and beta-glucuronidase. Corncob fiber (15%), treated with the fungus Pleurotus os., had a significant protective effect against DMH-induced rat colon cancer. This effect was accompanied by activation of some cellular mechanisms, i.e. apoptosis, proliferating cell nuclear antigen (PCNA) and p53 protein synthesis. A high positive correlation was found between tumor grade and p53 protein in the serum (r=0.97) or in the cell cytoplasm (r=0.77), and between tumor grade and PCNA (r=0.81). An inverse relationship was found between tumor grade and apoptosis (r=-0.63). ii) Experiments in mammary gland cancer showed that a 15% olive-oil diet reduced tumor incidence caused by 9,10-dimethyl-1,2-benzanthracene to 30%, compared with 55% in the control group. The antitumor effect of the olive oil diet was connected to its content of monounsaturated fatty acids, such as oleic and palmitic acids. The promotive tumorigenic effects of other high-fat diets (avocado, soybeans) were associated with high content of some polyunsaturated fatty acids (linoleic and alpha-linolenic). We concluded that different diets have different targets. The effect of the same diet depends on its content of anti-tumor substances.
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PMID:The role of dietary factors in prevention of chemically-induced cancers (review). 2152 16


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