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)

RMI 12,936 (7alpha-methyl-17beta-hydroxy-androst-5-en-one) was tested for androgenic activity in mouse kidney and for antiprogestational activity in guinea-pig uterus. RMI 12,936 stimulated an increase in kidney weight and in the activity of the androgen-responsive renal enzymes, beta-glucuronidase, alcohol dehydrogenase and arginase. RMI 12,936 was bound by the renal androgen receptor with a relative affinity approximately one-third that of testosterone. Although RMI 12,936 did not stimulate glycogen accumulation in guinea-pig endometrium in vivo, it was active in endometrial organ culture. When RMI 12,936 was combined with progesterone, glycogen accumulation in vitro was partly inhibited. RMI 12,936 was bound by the guinea-pig uterine progesterone receptor with a relative affinity of less than 1%. It is concluded that RMI 12,936 is an androgenic steroid with antifertility actions and in-vitro antiglycogenic activity.
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PMID:Androgenic effects of the antiprogestagen RMI 12,936. 63 20

Androgen controls the expression of beta-glucuronidase and several other proteins in the kidney of the standard laboratory mouse, Mus musculus. Other species within the genus Mus exhibit a variety of response patterns for kidney beta-glucuronidase and other markers of androgen action. We have investigated the mechanism of androgen action in M. caroli, a Mus species that does not produce beta-glucuronidase in response to testosterone. The failure of testosterone to induce beta-glucuronidase in M. caroli females cannot be overcome by treatment with dihydrotestosterone, with pharmacological doses of testosterone propionate or dihydrotestosterone propionate, or with a variety of potent androgen analogues. All of these compounds induce kidney beta-glucuronidase in M. musculus females and kidney ornithine decarboxylase, submandibular gland renin, and submandibular gland epidermal growth factor in both M. caroli and M. musculus females. Furthermore, kidney androgen receptor proteins from M. caroli and M. musculus animals have the same sedimentation characteristics on sucrose density gradients. These data indicate that androgen resistance in M. caroli is not due to deficient 5 alpha-reductase or aberrant hormone metabolism producing suboptimal levels of functional androgen and is not caused by a defective androgen receptor. They suggest that the resistance of beta-glucuronidase in M. caroli kidney to induction by androgen occurs at the level of the beta-glucuronidase gene.
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PMID:Specificity of androgen resistance in Mus caroli kidney. 307 98

Basal beta-glucuronidase activity was measured in the cytosol of renal cortex in 10 women and nine men, and its levels were correlated to the concentrations of the main circulating androgens and to the cytoplasmic androgen receptor content. beta-Glucuronidase activity in women was similar to that found in men, despite blood testosterone levels being higher in the latter. The activity of the enzyme does not appear to be related to circulating levels of either testosterone or androstenedione. Only in men the androgen receptor content and dehydroepiandrosterone-sulphate levels were inversely correlated to beta-glucuronidase. In the human kidney cytosol there is no evidence of sexual dimorphism in basal beta-glucuronidase activity; whereas the total testosterone circulating levels do not seem to control the enzyme activity.
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PMID:Androgen environment and beta-glucuronidase activity in the human kidney. 319 Mar 52

A method was developed for measuring in vivo rates of mRNA synthesis in mice by pulse-labeling with the RNA precursor [3H]orotate and then using hybridization to recover specific mRNAs. The efficiency of recovery is determined with synthetic RNAs as internal hybridization standards. The method is particularly applicable to the kidney since this organ shows a strong preferential uptake of the label. Rates of synthesis, expressed as a fraction of total RNA synthesis, were measured for the androgen-inducible mRNAs coding for beta-glucuronidase (GUS), ornithine decarboxylase (ODC), the protein coded by the RP-2 gene, and the so-called kidney androgen-regulated protein (KAP). Control mRNAs coded for beta-actin, phosphoenolpyruvate carboxykinase, and major urinary protein. Testosterone markedly increased the synthesis of the androgen-inducible mRNAs, but not the control mRNAs. Induction was not seen in mutant mice lacking functional androgen receptor protein. For GUS, ODC, and RP-2 mRNAs, the fold induction of synthesis was less than the fold induction of concentration, suggesting that mRNA stabilization also plays a part in the response to androgen. For GUS, ODC, and RP-2 mRNAs, but not KAP mRNA, induction of synthesis was rapidly reversed after testosterone removal. KAP mRNA was also exceptional in that its concentration was disproportionately high compared with its rate of synthesis, implying that it is a particularly stable mRNA.
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PMID:mRNA synthesis rates in vivo for androgen-inducible sequences in mouse kidney. 338 33

To examine the potential of steroid hormones to serve as putative regulators of aortic cell function, we defined hormone receptor content and distribution in intact baboons. Total androgen receptor content in baboon aortic arch, thoracic arch, and abdominal aorta of young mature males was indistinguishable from that of proestrus females. However, 30% to 40% of male aortic androgen receptors were in the nuclear fraction, whereas all aortic androgen receptors of proestrus females were in the cytoplasmic fraction. Cytoplasmic fraction estrogen receptor content of aortic arch and thoracic aorta of intact males was indistinguishable from that of proestrus females. However, cytoplasmic fraction estrogen receptor content of abdominal aorta of proestrus females was significantly greater than that of males. Nuclear fraction estrogen receptors were not detectable in either male or proestrus female baboon aortas. To assess effects of endogenous estrogen on aortic progesterone receptor content, we quantified cytoplasmic fraction progesterone receptors and found that content of proestrus female aortic arch was not significantly different from that of males. However, cytoplasmic fraction progesterone receptor content of thoracic and abdominal aorta of proestrus females was significantly higher than that of males. To determine whether differences in aortic receptor content or distribution were associated with changes in aortic cell function, we quantified the activity of two enzymes of glycosaminoglycan metabolism. Aortic beta-glucuronidase activity was not different in male or proestrus female baboons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gender and baboon aortic steroid hormone receptors. 359 71

The kidneys of androgen stimulated mice exhibit a hypertrophic response but no hyperplasia or concomitant DNA replication. Androgens increase the expression of several genes in mouse kidney. The response of the beta-glucuronidase gene to testosterone in this tissue is characterized by a 1-2 day lag and relatively slow induction kinetics. The gene coding for kidney androgen-regulated protein (KAP) exhibits quite a different response to the hormone when compared on the basis of initial response to a given dose, dose required to produce maximal response, and apparent sensitivity to low levels of androgen-receptor complexes in renal nuclei. The analysis of the accumulation of the mRNAs produced by these two genes suggests that gene-specific differential sensitivity to androgen receptor complexes governs the development of the cellular male phenotype in this tissue.
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PMID:Unique patterns of androgen regulation of the expression of two genes in murine kidney. 369 81

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

When 2-acetylaminofluorene and dimethylnitrosamine mutagenesis rates in the Salmonella/liver in vitro system were studied with C3H/HeJ mouse kidney or liver postmitochondrial supernatant (S-9) fractions, sex differences (male much greater than female) of 10- to 30-fold were found in kidney but not liver. We examined male mice castrated during the neonatal period, the Tfm/Y male, and dihydrotestosterone-treated female mice. The requirement of both testosterone and the androgen receptor is shown to be important in causing the sex difference in 2-acetylaminofluorene and dimethylnitrosamine mutagenesis in the kidney. Swank et al. [J Mol Biol 81:225-243 (1973)] demonstrated that dihydrotestosterone induces beta-glucuronidase activity in the female kidney: 28- to 30-fold in BALB/cJ and SM/J, 12-fold in C3H/HeJ, and 5- to 6-fold in C57BL/6J and RF/J inbred mice. This gene regulation has been characterized and named the Gur locus. 2-Acetylaminofluorene mutagenesis--in kidney but not liver--is markedly enhanced by dihydrotestosterone (P less than 0.01) in the first three, but not the latter three, inbred strains. Covalent binding of 2-acetylaminofluorene metabolites to DNA in the presence of kidney S-9 fractions in vitro is greatly increased in the BALB/cJ but not C57BL/6J female mouse pretreated with dihydrotestosterone. These data suggest that genetic differences at the Gur locus, in combination with the androgen receptor, may play an important role in the sex-specific and tissue-specific conversion of an O-glucuronide of N-hydroxy-2-acetylaminofluorene or N-hydroxy-aminofluorene to active mutagenic intermediates.
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PMID:Androgen receptor-mediated genetic differences in 2-acetylaminofluorene and dimethylnitrosamine mutagenesis in vitro. 665 Dec 31

beta-Glucuronidase mRNA was purified from androgen-induced mouse kidney by immunoadsorption of polysomes to protein A-Sepharose. Cell-free translation of mRNA isolated from the protein A bound RNA followed by immunoprecipitation revealed that beta-glucuronidase mRNA represented approximately 2% of the purified mRNA fraction. This mRNA preparation was used to produce complementary DNA clones by recombination with pBR322. Clones containing sequences that were enriched during the purification procedure were selected by differential colony hybridization. These were further screened for homology with beta-glucuronidase mRNA by hybrid-selected translation. A beta-glucuronidase cDNA clone, designated pGUS7, was identified by these criteria. With this plasmid, the abundance of beta-glucuronidase mRNA in total poly(A) mRNA from androgen-induced mouse kidney was estimated to be less than 0.04%. The beta-glucuronidase cDNA plasmid hybridized to a mRNA of 2.6 kb in length, which was induced in an androgen receptor dependent fashion over a time course of 21 days. Treatment of female mice with a single dose of testosterone (10 mg) revealed that beta-glucuronidase mRNA concentration begins to increase between 12 and 24 h after hormone administration.
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PMID:Detection of early changes in androgen-induced mouse renal beta-glucuronidase messenger ribonucleic acid using cloned complementary deoxyribonucleic acid. 668 71

Relative binding affinities (RBA) for the androgen receptor were estimated for levonorgestrel, progesterone, dihydrotestosterone, cyproterone acetate, 17 alpha-propylmesterolone and 3-keto-desogestrel (13-ethinyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol-3-one) which is the biological active metabolite of desogestrel. Mouse kidney cytosol served as receptor source. In addition, stimulation of mouse kidney beta-glucuronidase by subcutaneous injection of various doses of these compounds was determined. RBA for the androgen receptor of 3-keto-desogestrel was significantly greater (p less than 0.02) than that of levonorgestrel, and 3-keto-desogestrel was registered to enhance beta-glucuronidase activity more than levonorgestrel at the highest dose level (p less than 0.005). Furthermore, cyproterone acetate in the presence of testosterone was found to exert synandrogenic action at the lower dose level but suppressed enzyme activity at the higher doses. On the other hand, 17 alpha-propylmesterolone which had RBA similar to the one noted for cyproterone acetate showed only synandrogenic properties at the dose levels tested. The data combine to suggest that biological activity of a compound cannot be accurately predicted by receptor assays. Desogestrel and levonorgestrel exhibit similar androgenic properties in this model system. These data correlate with clinical experience on oral contraceptives containing levonorgestrel and desogestrel, respectively, which do not differ from each other in their androgen-related side effects.
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PMID:Androgenic action of progestins and possible synandrogenic properties of antiandrogens used in oral contraceptives. 670 45


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