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Glucuronidase estrogen

Karen Lee Ann Chen, Xiaoji Liu, Yiru Chen Zhao, Kadriye Hieronymi, Gianluigi Rossi, Loretta Sue Auvil, Michael Welge, Colleen Bushell, Rebecca Lee Smith, Kathryn E Carlson, Sung Hoon Kim, John A Katzenellenbogen, Michael Joseph Miller, Zeynep Madak-Erdogan
Conjugated estrogens (CE) and Bazedoxifene (BZA) combination is used to alleviate menopause-associated symptoms in women. CE+BZA undergo first-pass-metabolism in the liver and deconjugation by gut microbiome via β-glucuronidase (GUS) enzyme inside the distal gut. To date, the impact of long-term exposure to CE+BZA on the gut microbiome or GUS activity has not been examined. Our study using an ovariectomized mouse model showed that CE+BZA administration did not affect the overall cecal or fecal microbiome community except that it decreased the abundance of Akkermansia, which was identified as a fecal biomarker correlated with weight gain...
May 25, 2018: Scientific Reports
Jiufeng Li, Hongzhi Zhao, Yanqiu Zhou, Shunqing Xu, Zongwei Cai
Benzotriazole (BTR) and benzothiazole (BTH) derivatives are extensively applied in industrial processes and consumer products, and are thus frequently detected in the environmental matrices. Due to their potential estrogenic effects reported in animal studies, the assessment of human exposure to BTRs and BTHs is important. In this study, a method was developed and validated to determine six BTRs and five BTHs in human urine by using ultra-high performance liquid chromatography coupled with a triple quadrupole mass spectrometry (UHPLC-TQMS) in positive electrospray ionization mode...
December 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Atsushi Kaneko, Takashi Matsumoto, Yosuke Matsubara, Kyoji Sekiguchi, Junichi Koseki, Ryo Yakabe, Katsuyuki Aoki, Setsuya Aiba, Kenshi Yamasaki
INTRODUCTION: Flavonoids are converted to inactive metabolites like glucuronides in the gut, and circulate mainly as glucuronides in blood stream, resulting in low concentrations of active aglycones in plasma. It is therefore unclear how oral flavonoids exert their effects in tissues. We recently reported the plasma pharmacokinetics of some flavonoids and suggested the possibility that the absorbed flavonoids modified macrophage functions leading to enhance bacterial clearance. We aimed to confirm their pharmacological profiles focusing on tissue macrophages...
September 2017: Immunity, Inflammation and Disease
Juan Robles, Josep Marcos, Nuria Renau, Lorena Garrostas, Jordi Segura, Rosa Ventura, Bernardí Barceló, Antonia Barceló, Oscar J Pozo
A method for the quantitation of 22 urinary steroids (androgens, estrogens and the main pregnenolone and progesterone metabolites) by means of gas chromatography tandem mass spectrometry using a triple quadrupole analyzer has been developed. Two different enzymatic hydrolysis protocols were investigated; one capable of releasing steroids present as both sulfates and glucuronides (total fraction), and another with β-glucuronidase activity only. After selecting adequate internal standards and choosing the optimal instrumental parameters, i...
July 1, 2017: Talanta
Dinah Schick, Wolfgang Schwack
For the planar yeast estrogen screen (pYES), 4-methylumbelliferyl-β-d-galactopyranoside was generally employed as substrate, delivering blue fluorescing 4-methylumbelliferone after enzymatic cleavage by the YES reporter β-d-galactosidase as the positive signal for the presence of estrogen active compounds (EAC). As environmental samples like waste water also contain blue fluorescent components, it is difficult to differentiate them from pYES signals. Therefore, resorufin-β-d-galactopyranoside (RGP), providing the orange fluorescing resorufin after enzymatic cleavage, was introduced as pYES substrate to determine EAC...
May 12, 2017: Journal of Chromatography. A
Sergey V Popov, Pavel A Markov, Olga A Patova, Fedor V Vityazev, Larisa A Bakutova, Mikhail F Borisenkov, Ekaterina A Martinson, Boris A Ananchenko, Eugene A Durnev, Andrey A Burkov, Sergey G Litvinets, Vladimir A Belyi, Elena A Ipatova
Pectin hydrogel particles (PHPs) were prepared by ionotropic gelation of low methylesterified pectin of Tanacetum vulgare L. with calcium ions. Wet PHPs prepared from TVF exhibited a smaller diameter and the lower weight as well as exhibited the best textural properties in terms of hardness and elasticity compared to the PHPs prepared from commercial low methylesterified pectin (CU701) used for comparison. Upon air drying, PHPs prepared from CU701 became small and dense microspheres whereas the dry PHPs prepared from TVF exhibited a drop-like shape...
February 2017: Journal of Biomaterials Science. Polymer Edition
Elias Baydoun, Atia-Tul Wahab, Nayab Shoaib, Malik Shoaib Ahmad, Roula Abdel-Massih, Colin Smith, Nimra Naveed, M Iqbal Choudhary
Biotransformation of a steroidal contraceptive drug, etonogestrel (1), (13-ethyl-17β-hydroxy-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3-one) was investigated with Cunninghamella blakesleeana and C. echinulata. Five metabolites 2-6 were obtained on incubation of 1 with Cunninghamella blakesleeana, and three metabolites, 2, 4, and 6 were isolated from the transformation of 1 with C. echinulata. Among them, metabolites 2-4 were identified as new compounds. Their structures were deduced as 6β-hydroxy-11,22-epoxy-etonogestrel (2), 11,22-epoxy-etonogestrel (3), 10β-hydroxy-etonogestrel (4), 6β-hydroxy-etonogestrel (5), and 14α-hydroxy-etonogestrel (6)...
November 2016: Steroids
Monika Drastikova, Martin Beranek, Filip Gabalec, David Netuka, Vaclav Masopust, Tomas Cesak, Josef Marek, Vladimir Palicka, Jan Cap
AIMS: Pituitary adenomas (PA) are non-invasive benign tumors with a high autopsy prevalence. They are classified according to the type of hormone secreted (prolactin, growth hormone, adrenocorticotropin, thyrotropin, folitropin, or luteinizing hormone). Clinically non-functioning adenomas (CNFA) lacking the typical hypersecretion of hormones make up a significant portion of PA. The aim of the study was to determine the complete expression profiles of somatostatin receptors (SSTR1-SSTR5), dopamine receptors type 2 (D2R), and estrogen receptors (ER1) in various types of PA...
June 2016: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
Masato Okano, Mitsuhiko Sato, Asami Kojima, Shinji Kageyama
Mepitiostane (2α,3α-epithio-17β-(1-methoxycyclopentyloxy)-5α-androstane), which is a prodrug of epitiostanol (2α,3α-epitio-5α-androstane-17β-ol), is an epitiosteroid having anti-estrogenic and weak androgenic anabolic activities. The World Anti-Doping Agency prohibits the misuse of mepitiostane by athletes. Detection of the urinary metabolites epitiostanol sulfoxide and epitiostanol was studied using liquid chromatography/mass spectrometry (LC-MS) for doping control purposes. The use of LC-MS provided advantages over gas chromatography/mass spectrometry for detecting heat labile steroids because epitiostanol and epitiostanol sulfoxide were primarily pyrolized to 5α-androst-2-en-17β-ol...
November 10, 2015: Journal of Pharmaceutical and Biomedical Analysis
Oihana Ros, Josu Aguirre, Ailette Prieto, Maitane Olivares, Nestor Etxebarria, Asier Vallejo
This study describes a new method for the simultaneous extraction and enzymatic hydrolysis of alkylphenols, estrogens, bisphenol-A and phthalate metabolite (mono-2-ethylhexyl ester, MEHP) in fish bile using polyethersulfone (PES) polymer as sorptive material. Parameters affecting the hydrolysis (enzyme amount) and extraction (nature of polymeric material, PES desorption solvent nature and time, PES amount and time profile) were optimised. The optimum conditions were fixed as: 5 PES tubes (1.5 cm length × 0...
September 2015: Analytical and Bioanalytical Chemistry
Alicia Romero-Lorca, Apolonia Novillo, María Gaibar, Fernando Bandrés, Ana Fernández-Santander
Tamoxifen is used to prevent and treat estrogen-dependent breast cancer. It is described as a prodrug since most of its antiestrogen effects are exerted through its hydroxylated metabolites 4-OH-tamoxifen and endoxifen. In prior work, we correlated optimal plasma levels of these metabolites with certain genotypes of CYP2D6 and SULT1A2. This descriptive study examines correlations between concentrations of tamoxifen's glucuronide metabolites and genotypes UGT1A4 Pro24Thr, UGT1A4 Leu48Val, UGT2B7 His268Tyr, UGT2B15 Asp85YTyr UGT2B15 Lys523Thr and UGT2B17del in 132 patients with estrogen receptor-positive breast cancer under treatment with tamoxifen...
2015: PloS One
L P Madhubhani P Hemachandra, Hitisha Patel, R Esala P Chandrasena, Jaewoo Choi, Sujeewa C Piyankarage, Shuai Wang, Yijin Wang, Emily N Thayer, Robert A Scism, Bradley T Michalsen, Rui Xiong, Marton I Siklos, Judy L Bolton, Gregory R J Thatcher
The risk of developing hormone-dependent cancers with long-term exposure to estrogens is attributed both to proliferative, hormonal actions at the estrogen receptor (ER) and to chemical carcinogenesis elicited by genotoxic, oxidative estrogen metabolites. Nontumorigenic MCF-10A human breast epithelial cells are classified as ER(-) and undergo estrogen-induced malignant transformation. Selective estrogen receptor modulators (SERM), in use for breast cancer chemoprevention and for postmenopausal osteoporosis, were observed to inhibit malignant transformation, as measured by anchorage-independent colony growth...
May 2014: Cancer Prevention Research
Fangqing Zhou, Lin Zhang, Ai Liu, Yang Shen, Jinpeng Yuan, Xiaojin Yu, Xu Feng, Qian Xu, Chuange Cheng
A method was established for the determination of three phenolic environmental estrogens, namely bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP), in urine from women of uterine leiomyoma group (n=49) and control group (n=29), by using solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urine samples were spiked with 2,4,6-tribromophenyl-terminated tetrabromobisphenol-A carbonate oligomer (TBBPA) and nonylphenol D8 (NP-D8) as internal standard (I.S...
November 1, 2013: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Moshe Matan, Elena Axelman, Benjamin Brenner, Yona Nadir
STUDY QUESTION: What is the effect of estrogen on heparanase procogulant activity? SUMMARY ANSWER: Estrogen increases heparanase procoagulant activity. WHAT IS KNOWN ALREADY: Estrogen therapy increases the risk of thrombosis and was previously found to up-regulate heparanase expression. Heparanase is involved in angiogenesis and metastasis, and has been shown to form a complex with tissue factor (TF) and also shown to enhance the generation of factor Xa...
September 2013: Human Reproduction
Ting-Ting Chen, Tai-Yuan Huang, Ryh-Nan Pan, Guo-Ping Chang-Chien, Mei-Chich Hsu
Raloxifene is one of the selective estrogen receptor modulators and is often used to prevent and treat osteoporosis in postmenopausal women. Because of the indirect impact on serum testosterone levels and the potential ability for performance enhancement, it is banned by the World Anti-Doping Agency (WADA). This study established a fast, sensitive and selective liquid chromatography-tandem mass spectrometry method to quantify total raloxifene (unchanged and glucuronidated) in human urine for doping analysis...
July 2013: Journal of Analytical Toxicology
Roberto Flores, Jianxin Shi, Barbara Fuhrman, Xia Xu, Timothy D Veenstra, Mitchell H Gail, Pawel Gajer, Jacques Ravel, James J Goedert
BACKGROUND: High systemic estrogen levels contribute to breast cancer risk for postmenopausal women, whereas low levels contribute to osteoporosis risk. Except for obesity, determinants of non-ovarian systemic estrogen levels are undefined. We sought to identify members and functions of the intestinal microbial community associated with estrogen levels via enterohepatic recirculation. METHODS: Fifty-one epidemiologists at the National Institutes of Health, including 25 men, 7 postmenopausal women, and 19 premenopausal women, provided urine and aliquots of feces, using methods proven to yield accurate and reproducible results...
2012: Journal of Translational Medicine
Muna S Nahar, Chunyang Liao, Kurunthachalam Kannan, Dana C Dolinoy
Widespread exposure to the endocrine active compound, bisphenol A (BPA), is well documented in humans. A growing body of literature suggests adverse health outcomes associated with varying ranges of exposure to BPA. In the current study, we measured the internal dose of free BPA and conjugated BPA and evaluated gene expression of biotransformation enzymes specific for BPA metabolism in 50 first- and second-trimester human fetal liver samples. Both free BPA and conjugated BPA concentrations varied widely, with free BPA exhibiting three times higher concentrations than conjugated BPA concentrations...
February 2013: Journal of Biochemical and Molecular Toxicology
Estatira Sepehr, Marketa Lebl-Rinnova, Meagan K Mann, Samantha L Pisani, Mona I Churchwell, Donna L Korol, John A Katzenellenbogen, Daniel R Doerge
Estrogen receptor (ER) subtype specific agonists, diarylpropionitrile (DPN) for ERβ and propylpyrazoletriol (PPT) for ERα, are pharmacological probes used frequently to define mechanisms for estrogen actions in vitro and in vivo. Quantitative analytical methodology was developed and validated for DPN and PPT, based on synthetic stable labeled analogs (DPN-d(4) and PPT-d(5)) using isotope dilution liquid chromatographic tandem electrospray mass spectrometric detection. The validated method produced high sensitivity, with detection limits of 0...
December 2012: Journal of Pharmaceutical and Biomedical Analysis
Harini Chowdary Vadlamudi, Y Prasanna Raju, B Rubia Yasmeen, Jayasri Vulava
The colon is composed of four distinct layers such as serosa, muscularis externa, sub mucosa and mucosa. There exists a difference in the anatomy, neural and blood supply and absorption characteristics as the length of the colon is traversed. At birth the mucosal surface of the colon is similar to that of the small intestine but rapid changes occur with the loss of the villi leaving flat mucosa with deep crypts. The existence of receptors like muscarinic M3, cholecystokinin1, Eph, Erb B, estrogen (α, β), gastrin releasing peptide, killer Ig like receptor, lymphocyte-endothelial receptor, notch, pregnane X, substance P and peroxisome proliferator-activated γ receptor can be utilized as a promising approach for targeting...
November 2012: Current Drug Delivery
David Hala, Lene H Petersen, Dalma Martinovic, Duane B Huggett
In this study, an in silico genome-scale metabolic model of steroidogenesis was used to investigate the effects of hypoxic stress on steroid hormone productions in fish. Adult female fathead minnows (Pimephales promelas) were exposed to hypoxia for 7 days with fish sub-sampled on days 1, 3 and 7 of exposure. At each time point, selected steroid enzyme gene expressions and steroid hormone productions were quantified in ovaries. Fold changes in steroid enzyme gene expressions were used to qualitatively scale transcript enzyme reaction constraints (akin to the range of an enzyme's catalytic activity) in the in silico model...
May 15, 2012: Journal of Experimental Biology
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