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

Metabolism of tamoxifen by rat hepatocytes and hydrolysis of the resulting polar metabolites corresponding to conjugates with beta-glucuronidase gave a major component which was identified as 1-[4-(2-hydroxyethoxy)phenyl]-1-(4-hydroxyphenyl)-2-phenyl-1-butene by comparison of mass spectral properties with those of synthetic material. This compound, which was not observed as a phase I metabolite, is believed to have been found previously in rat bile and in human faeces (metabolite F) but its structure had been incorrectly assigned. Its binding affinity for the estrogen receptor was greater than that of tamoxifen but less than that of 4-hydroxytamoxifen, and it possessed a corresponding degree of antitumour activity against the MCF-7 breast cancer cell line. By carrying out the hepatocyte incubation separately under oxygen and air, it has been shown that the N-oxidation of tamoxifen is favoured by a high concentration of oxygen during in vitro metabolism but that the rate of 4-hydroxylation is not dependent on oxygen availability.
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PMID:Metabolism of tamoxifen by isolated rat hepatocytes. Identification of 1-[4-(2-hydroxyethoxy)phenyl]-1-(4-hydroxyphenyl)-2-phenyl-1-butene and the dependence of N-oxidation on oxygen availability. 357 87

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

BRCA1 and BRCA2 mRNA expression in sporadic breast cancers was quantified by a real-time reverse transcriptase-polymerase chain reaction (RT-PCR), and the relationship of their expression with various clinicopathological factors was studied. BRCA2 mRNA levels (0.993 +/- 1.395, mean +/- SD (BRCA2 / beta-glucuronidase mRNA ratios)) were significantly (P < 0.01) higher than BRCA1 mRNA levels (0.519 +/- 0.570 (BRCA1 / beta-glucuronidase mRNA ratios)), and a weak but significant (r = 0.390, P < 0.01) correlation was observed between BRCA1 and BRCA2 mRNA expression levels. There was no significant association between BRCA1 mRNA expression and clinicopathological factors such as menstrual status, tumor size, lymph node status, estrogen and progesterone receptor status, and histological grade. On the other hand, there was a significant association between higher BRCA2 mRNA expression and estrogen receptor (ER) negativity (P < 0.01) or progesterone receptor (PR) negativity (P < 0.01) or high histological grade (P < 0.01). These results suggest a differential contribution of BRCA1 and BRCA2 in the pathogenesis of sporadic breast cancers. BRCA2 mRNA is speculated to be up-regulated in response to proliferation and genomic instability in high histological grade tumors.
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PMID:Quantitative analysis of BRCA1 and BRCA2 mRNA expression in sporadic breast carcinomas and its relationship with clinicopathological characteristics. 1142 50

Although estrogens are excreted as biologically inactive conjugates, they can be reconverted to an active form, possibly by bacteria. A simple method was developed to deconjugate estrogen metabolites present in human urine and fish bile back to active estrogens by enzymatic hydrolysis with beta-glucuronidase or live Escherichia coli cells. Deconjugated extracts were tested for estrogenic activity in the in vitro stable estrogen receptor-mediated chemical-activated luciferase gene expression (ER-CALUX) assay. Estrogen glucuronides in urine obtained from human males and females were effectively converted to active forms after incubation with beta-glucuronidase or E. coli. The highest estrogenic activity was found in deconjugated metabolites from urine of a pregnant woman, in which levels up to 3,000 nmol estradiol equivalents per liter of urine were found after overnight incubation of urine with E. coli. Bile sampled from male bream and flounder from various freshwater and marine locations was also deconjugated and a good correlation was found between high biliary estrogenic activity and elevated levels of xenoestrogenic activity in surface water as well as in plasma vitellogenin. Therefore, the measurement of deconjugated bile could form a useful (indirect) biomarker for internal dose of xenoestrogens in male fish.
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PMID:Biological measurement of estrogenic activity in urine and bile conjugates with the in vitro ER-CALUX reporter gene assay. 1187 59

The prognostic significance of BRCA2 mRNA levels in tumor tissues was studied in sporadic breast cancer patients. BRCA2 mRNA levels were determined by real-time PCR. Histologic grade III tumors showed significantly (p = 0.001) higher BRCA2 mRNA levels (0.828 +/- 0.102 BRCA2/beta-glucuronidase mRNA ratio, mean +/- SE) than histologic grade I and II tumors (0.438 +/- 0.055) and estrogen receptor (ER)-negative tumors (0.773 +/- 0.102) showed a nonsignificant (p = 0.072) trend toward an increase in BRCA2 mRNA levels compared to ER-positive tumors (0.541 +/- 0.079). Other clinicopathologic parameters, such as menopausal status, lymph node status and tumor size, were not significantly associated with BRCA2 mRNA levels. Patients with high BRCA2 mRNA levels showed a significantly (p = 0.006) lower 5-year disease free survival rate (63%) than those with low levels (94%). Lymph node metastases, ER negativity and high histologic grade were also significantly (p < 0.05) associated with poor prognosis. Multivariate analysis revealed that BRCA2 mRNA levels were a significant prognostic factor, being independent of the other conventional prognostic factors. Our results suggest that BRCA2 mRNA levels might serve as a clinically useful prognostic factor in breast cancer patients.
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PMID:High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients. 1194 66

Numerous physiological processes are regulated by endocrine systems in animals. Endocrine-disrupting chemicals (EDCs) can affect physiological processes of organisms by binding to hormone receptors. Therefore, it is necessary to develop methods for detecting EDCs and removing them from the environment. We have developed a simple and low-cost reporter gene assay system for the comprehensive analysis of estrogenic activity using transgenic Arabidopsis thaliana. This transgenic plant constantly expresses two effector proteins: a chimeric estrogen receptor and a chimeric nuclear receptor coactivator. Estrogen-dependent interaction between the two effector proteins triggers transcriptional activation of reporter gene, beta-glucuronidase. We have demonstrated this transgenic plant's capability of detecting the existence of 17beta-estradiol at a concentration of 50 pM (13 pg/ml) in agar medium. This plant can also detect other estrogenic substances, such as diethylstilbestrol, p-n-nonylphenol, bisphenol A, and Genistein.
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PMID:A simple and extremely sensitive system for detecting estrogenic activity using transgenic Arabidopsis thaliana. 1640 77