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[PMID]:28980890
[Au] Autor:Takagi S; Naito M; Kawai S; Okada R; Nagata C; Hosono S; Nishida Y; Takashima N; Suzuki S; Shimoshikiryo I; Mikami H; Uemura H; Kuriyama N; Ohnaka K; Kubo M; Hamajima N; Tanaka H; Wakai K
[Ad] Endereço:1Department of Preventive Medicine,Nagoya University Graduate School of Medicine,65 Tsurumai-cho,Showa-ku,Nagoya 466-8550,Japan.
[Ti] Título:Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women.
[So] Source:Br J Nutr;118(6):463-472, 2017 Sep.
[Is] ISSN:1475-2662
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.
[Mh] Termos MeSH primário: Aromatase/genética
Grupo com Ancestrais do Continente Asiático/genética
Dieta
Estradiol Desidrogenases/genética
Estrogênios/sangue
Polimorfismo de Nucleotídeo Único
Pós-Menopausa/sangue
[Mh] Termos MeSH secundário: Idoso
Animais
Estudos Transversais
Carboidratos da Dieta/administração & dosagem
Gorduras na Dieta/administração & dosagem
Proteínas na Dieta/administração & dosagem
Estradiol/sangue
Ácidos Graxos/administração & dosagem
Ácidos Graxos/sangue
Ácidos Graxos Ômega-3/administração & dosagem
Ácidos Graxos Ômega-3/sangue
Feminino
Peixes
Técnicas de Genotipagem
Seres Humanos
Japão
Estilo de Vida
Modelos Lineares
Meia-Idade
Alimentos Marinhos
Inquéritos e Questionários
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dietary Carbohydrates); 0 (Dietary Fats); 0 (Dietary Proteins); 0 (Estrogens); 0 (Fatty Acids); 0 (Fatty Acids, Omega-3); 4TI98Z838E (Estradiol); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.1.1.62 (HSD17B1 protein, human); EC 1.14.14.1 (Aromatase); EC 1.14.14.1 (CYP19A1 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE
[do] DOI:10.1017/S0007114517002239


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[PMID]:28800957
[Au] Autor:Trottier A; Maltais R; Ayan D; Barbeau X; Roy J; Perreault M; Poulin R; Lagüe P; Poirier D
[Ad] Endereço:Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec - Research Center (CHUL, T4), Québec, QC, Canada.
[Ti] Título:Insight into the mode of action and selectivity of PBRM, a covalent steroidal inhibitor of 17ß-hydroxysteroid dehydrogenase type 1.
[So] Source:Biochem Pharmacol;144:149-161, 2017 Nov 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:17ß-Hydroxysteroid dehydrogenase type 1 (17ß-HSD1) is involved in the biosynthesis of estradiol, the major bioactive endogenous estrogen in mammals, and constitutes an interesting therapeutic target for estrogen-dependent diseases. A steroidal derivative, 3-{[(16ß,17ß)-3-(2-bromoethyl)-17-hydroxyestra-1,3,5(10)-trien-16-yl]methyl} benzamide (PBRM), has recently been described as a non-estrogenic, irreversible inhibitor of 17ß-HSD1. However, the mode of action of this inhibitor and its selectivity profile have not yet been elucidated. We assessed PBRM potency via in vitro kinetic measurements. The mechanism of enzyme inactivation was also investigated using interspecies (human, mouse, pig and monkey) comparisons via both in vitro assays and in silico analysis. Mouse and human plasma protein binding of PBRM was determined, whereas its selectivity of action was studied using a wide range of potential off-targets (e.g. GPCR, hERG, CYPs, etc.). The affinity constant (K =368nM) and the enzyme inactivation rate (k =0.087min ) values for PBRM were determined with purified 17ß-HSD1. PBRM was found to be covalently linked to the enzyme. A long delay period (i.e. 3-5days) is required to recover 17ß-HSD1 activity following a pretreatment of breast and placenta cell lines with PBRM. Mechanistic analyses showed important interspecies differences of 17ß-HSD1 inhibition which support the importance of inactivation for PBRM effect. Evidences of the potency and selectivity of action presented herein for this first non-estrogenic and steroidal covalent irreversible inhibitor of 17ß-HSD1 warrant its further development as a potential drug candidate for estrogen-dependent disorders.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/metabolismo
Inibidores Enzimáticos/farmacologia
Estradiol Desidrogenases/antagonistas & inibidores
Estradiol Desidrogenases/metabolismo
[Mh] Termos MeSH secundário: Animais
Benzamidas/química
Benzamidas/metabolismo
Benzamidas/farmacologia
Callithrix
Linhagem Celular Tumoral
Inibidores Enzimáticos/química
Feminino
Células HEK293
Haplorrinos
Seres Humanos
Camundongos
Ligação Proteica/fisiologia
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamides); 0 (Enzyme Inhibitors); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.1.1.62 (HSD17B1 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170813
[St] Status:MEDLINE


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[PMID]:28552583
[Au] Autor:Chen YL; Yu CP; Lee TH; Goh KS; Chu KH; Wang PH; Ismail W; Shih CJ; Chiang YR
[Ad] Endereço:Biodiversity Research Center, Academia Sinica, 128 Academia Road Section 2, Nankang, Taipei 115, Taiwan; Department of Life Science, National Taiwan Normal University, Taipei 106, Taiwan; Biodiversity Program, Taiwan International Graduate Program, Academia Sinica and National Taiwan Normal Universi
[Ti] Título:Biochemical Mechanisms and Catabolic Enzymes Involved in Bacterial Estrogen Degradation Pathways.
[So] Source:Cell Chem Biol;24(6):712-724.e7, 2017 Jun 22.
[Is] ISSN:2451-9456
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Estrogens have been classified as group 1 carcinogens by the World Health Organization and represent a significant concern given that they are found in surface waters worldwide, and long-term exposure to estrogen-contaminated water can disrupt sexual development in animals. To date, the estrogen catabolic enzymes and genes remain unknown. Using a tiered functional genomics approach, we identified three estrogen catabolic gene clusters in Sphingomonas sp. strain KC8. We identified several estrone-derived compounds, including 4-hydroxyestrone, a meta-cleavage product, and pyridinestrone acid. The yeast-based estrogen assay suggested that pyridinestrone acid exhibits negligible estrogenic activity. We characterized 17ß-estradiol dehydrogenase and 4-hydroxyestrone 4,5-dioxygenase, responsible for the 17-dehydrogenation and meta-cleavage of the estrogen A ring, respectively. The characteristic pyridinestrone acid was detected in estrone-spiked samples collected from two wastewater treatment plants and two suburban rivers in Taiwan. The results significantly expand our understanding of microbial degradation of aromatic steroids at molecular level.
[Mh] Termos MeSH primário: Dioxigenases/metabolismo
Estradiol Desidrogenases/metabolismo
Estrogênios/isolamento & purificação
Estrogênios/metabolismo
Sphingomonas/metabolismo
Poluentes Químicos da Água/isolamento & purificação
Poluentes Químicos da Água/metabolismo
[Mh] Termos MeSH secundário: Biodegradação Ambiental
Dioxigenases/genética
Estradiol Desidrogenases/genética
Sphingomonas/enzimologia
Sphingomonas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Estrogens); 0 (Water Pollutants, Chemical); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.13.11.- (Dioxygenases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE


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[PMID]:28506753
[Au] Autor:Vuorinen A; Engeli RT; Leugger S; Kreutz CR; Schuster D; Odermatt A; Matuszczak B
[Ad] Endereço:Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056
[Ti] Título:Phenylbenzenesulfonates and -sulfonamides as 17ß-hydroxysteroid dehydrogenase type 2 inhibitors: Synthesis and SAR-analysis.
[So] Source:Bioorg Med Chem Lett;27(13):2982-2985, 2017 07 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:17ß-Hydroxysteroid dehydrogenase type 2 (17ß-HSD2) converts the potent estrogen estradiol into the weakly active keto form estrone. Because of its expression in bone, inhibition of 17ß-HSD2 provides an attractive strategy for the treatment of osteoporosis, a condition that is often caused by a decrease of the active sex steroids. Currently, there are no drugs on the market targeting 17ß-HSD2, but in multiple studies, synthesis and biological evaluation of promising 17ß-HSD2 inhibitors have been reported. Our previous work led to the identification of phenylbenzenesulfonamides and -sulfonates as new 17ß-HSD2 inhibitors by ligand-based pharmacophore modeling and virtual screening. In this study, new molecules representing this scaffold were synthesized and tested in vitro for their 17ß-HSD2 activity to derive more profound structure-activity relationship rules.
[Mh] Termos MeSH primário: Benzenossulfonatos/farmacologia
Inibidores Enzimáticos/farmacologia
Estradiol Desidrogenases/antagonistas & inibidores
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Benzenossulfonatos/síntese química
Benzenossulfonatos/química
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Estradiol Desidrogenases/metabolismo
Seres Humanos
Estrutura Molecular
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzenesulfonates); 0 (Enzyme Inhibitors); 0 (Sulfonamides); 0 (phenylbenzenesulfonate); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.1.1.62 (HSD17B2 protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170517
[St] Status:MEDLINE


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[PMID]:28381288
[Au] Autor:Adibi JJ; Buckley JP; Lee MK; Williams PL; Just AC; Zhao Y; Bhat HK; Whyatt RM
[Ad] Endereço:Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, Parran Hall 5132, Pittsburgh, PA, 15261, USA. adibij@pitt.edu.
[Ti] Título:Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort.
[So] Source:Environ Health;16(1):35, 2017 Apr 05.
[Is] ISSN:1476-069X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Prenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may offer biologic insight into these associations. This is the first study to address these associations with candidate genes from the phthalate and placenta literature, accounting for sex differences, and using absolute quantitation methods for mRNA levels. METHODS: We measured candidate mRNAs in 180 placentas sampled at birth (HSD17B1, AHR, CGA, CYP19A1, SLC27A4, PTGS2, PPARG, CYP11A1) by quantitative PCR and an absolute standard curve. We estimated associations of log mRNA with quartiles of urinary phthalate monoesters using linear mixed models. Phthalate metabolites (N = 358) and mRNAs (N = 180) were transformed to a z-score and modeled as independent, correlated vectors in relation to large for gestational age (LGA) and gestational diabetes mellitus (GDM). RESULTS: CGA was associated with 4 out of 6 urinary phthalates. CGA was 2.0 log units lower at the 3 vs. 1 quartile of mono-n-butyl phthalate (MnBP) (95% confidence interval (CI): -3.5, -0.5) in male placentas, but 0.6 log units higher (95% CI: -0.8, 1.9) in female placentas (sex interaction p = 0.01). There was an inverse association of MnBP with PPARG in male placentas (-1.1 log units at highest vs. lowest quartile, 95% CI: -2.0, -0.1). CY19A1, CYP11A1, CGA were associated with one or more of the following in a sex-specific manner: monobenzyl phthalate (MBzP), MnBP, mono-iso-butyl phthalate (MiBP). These 3 mRNAs were lower by 1.4-fold (95% CI: -2.4, -1.0) in male GDM placentas vs. female and non-GDM placentas (p-value for interaction = 0.04). The metabolites MnBP/MiBP were 16% higher (95% CI: 0, 22) in GDM pregnancies. CONCLUSIONS: Prenatal concentrations of certain phthalates and outcomes at birth were modestly associated with molecular changes in fetal placental tissue during pregnancy. Associations were stronger in male vs. female placentas, and associations with MnBP and MiBP were stronger than other metabolites. Placental mRNAs are being pursued further as potential mediators of exposure-induced risks to the health of the child.
[Mh] Termos MeSH primário: Poluentes Ambientais/urina
Exposição Materna
Ácidos Ftálicos/urina
Placenta/metabolismo
RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Adulto
Aromatase/genética
Enzima de Clivagem da Cadeia Lateral do Colesterol/genética
Estradiol Desidrogenases/genética
Proteínas de Transporte de Ácido Graxo/genética
Feminino
Expressão Gênica
Subunidade alfa de Hormônios Glicoproteicos/genética
Seres Humanos
Masculino
PPAR gama/genética
Gravidez
Receptores de Hidrocarboneto Arílico/genética
Caracteres Sexuais
População Urbana
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Environmental Pollutants); 0 (Fatty Acid Transport Proteins); 0 (Glycoprotein Hormones, alpha Subunit); 0 (PPAR gamma); 0 (Phthalic Acids); 0 (RNA, Messenger); 0 (Receptors, Aryl Hydrocarbon); 0 (SLC27A4 protein, human); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.1.1.62 (HSD17B1 protein, human); EC 1.14.14.1 (Aromatase); EC 1.14.14.1 (CYP19A1 protein, human); EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1186/s12940-017-0241-5


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[PMID]:28329705
[Au] Autor:McFarland AP; Luo S; Ahmed-Qadri F; Zuck M; Thayer EF; Goo YA; Hybiske K; Tong L; Woodward JJ
[Ad] Endereço:Department of Microbiology, University of Washington, Seattle, WA 98195, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
[Ti] Título:Sensing of Bacterial Cyclic Dinucleotides by the Oxidoreductase RECON Promotes NF-κB Activation and Shapes a Proinflammatory Antibacterial State.
[So] Source:Immunity;46(3):433-445, 2017 Mar 21.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bacterial and host cyclic dinucleotides (cdNs) mediate cytosolic immune responses through the STING signaling pathway, although evidence suggests that alternative pathways exist. We used cdN-conjugated beads to biochemically isolate host receptors for bacterial cdNs, and we identified the oxidoreductase RECON. High-affinity cdN binding inhibited RECON enzyme activity by simultaneously blocking the substrate and cosubstrate sites, as revealed by structural analyses. During bacterial infection of macrophages, RECON antagonized STING activation by acting as a molecular sink for cdNs. Bacterial infection of hepatocytes, which do not express STING, revealed that RECON negatively regulates NF-κB activation. Loss of RECON activity, via genetic ablation or inhibition by cdNs, increased NF-κB activation and reduced bacterial survival, suggesting that cdN inhibition of RECON promotes a proinflammatory, antibacterial state that is distinct from the antiviral state associated with STING activation. Thus, RECON functions as a cytosolic sensor for bacterial cdNs, shaping inflammatory gene activation via its effects on STING and NF-κB.
[Mh] Termos MeSH primário: Infecções Bacterianas/imunologia
Proteínas de Bactérias/imunologia
Estradiol Desidrogenases/imunologia
Inflamação/imunologia
NF-kappa B/imunologia
[Mh] Termos MeSH secundário: Animais
Ativação Enzimática/imunologia
Macrófagos/imunologia
Camundongos
Camundongos Knockout
NF-kappa B/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (NF-kappa B); EC 1.1.1.62 (AKR1C13 protein, mouse); EC 1.1.1.62 (Estradiol Dehydrogenases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE


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[PMID]:28039834
[Au] Autor:Li J; Chang J; Li W; Guo B; Li J; Wang H
[Ad] Endereço:Research Center for Eco-Environmental Science, Chinese Academy of Sciences, Shuangqing Rd 18, Beijing 100085, China; University of Chinese Academy of Sciences, Yuquan Rd 19A, Beijing, 100049, China.
[Ti] Título:Disruption of sex-hormone levels and steroidogenic-related gene expression on Mongolia Racerunner (Eremias argus) after exposure to triadimefon and its enantiomers.
[So] Source:Chemosphere;171:554-563, 2017 Mar.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Triadimefon (TF) is a widely used chiral fungicide with one chiral centre and two enantiomers (TF and TF ). However, little is reported about the ecological toxicity of reptiles on an enantioselective level. TF is a potential endocrine disruptor that may interfere with sex steroid hormones, such as testosterone (T) and 17beta-estradiol (E ). In our study, the lizards Mongolia Racerunner (Eremias argus) were orally exposed to TF and its enantiomers for 21 days. Plasma sex steroid hormones and steroidogenic-related genes, including 17-beta-hydroxysteroid (hsd17ß), cytochrome P450 enzymes (cyp19 and cyp17), and steroid hormone receptors (erα and Ar) were evaluated. After exposure, the plasma testosterone level in the 100 mg/kg group was elevated, while the oestradiol level was reduced. This phenomenon may be caused by the transformation of cyp19, which may inhibit the conversion of testosterone to oestradiol and affect sexual behaviour. In addition, the two enantiomers have different effects on hormone levels, which testified to the previously reported biotoxic dissimilarity between TF and TF in organisms. Furthermore, the cyp19 mRNA level in liver and gonad of the TF and TF group (100 mg/kg ) were significantly down-regulated, while the cyp17 and hsd17ß mRNA levels were up-regulated. The expression of erα and Ar mRNA levels were up-regulated in males but not in females, which may indicate that TF has sex differences on these two genes. As seen from the above results, TF and its enantiomers may have endocrine-disrupting effects on lizards (E. argus) by acting sensitively on sex steroid hormones and steroidogenic-related genes.
[Mh] Termos MeSH primário: Disruptores Endócrinos/toxicidade
Fungicidas Industriais/toxicidade
Lagartos
Triazóis/toxicidade
[Mh] Termos MeSH secundário: Animais
Aromatase/genética
Disruptores Endócrinos/química
Estradiol/sangue
Estradiol Desidrogenases/genética
Receptor alfa de Estrogênio/genética
Feminino
Fungicidas Industriais/química
Regulação da Expressão Gênica/efeitos dos fármacos
Gônadas/efeitos dos fármacos
Gônadas/metabolismo
Fígado/efeitos dos fármacos
Fígado/metabolismo
Lagartos/sangue
Lagartos/genética
Masculino
RNA Mensageiro/metabolismo
Receptores Androgênicos/genética
Estereoisomerismo
Esteroide 17-alfa-Hidroxilase/genética
Testosterona/sangue
Triazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Endocrine Disruptors); 0 (Estrogen Receptor alpha); 0 (Fungicides, Industrial); 0 (RNA, Messenger); 0 (Receptors, Androgen); 0 (Triazoles); 1HW039CJF0 (triadimefon); 3XMK78S47O (Testosterone); 4TI98Z838E (Estradiol); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.14.14.1 (Aromatase); EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170427
[Lr] Data última revisão:
170427
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170101
[St] Status:MEDLINE


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[PMID]:27923582
[Au] Autor:Cornel KM; Krakstad C; Delvoux B; Xanthoulea S; Jori B; Bongers MY; Konings GF; Kooreman LF; Kruitwagen RF; Salvesen HB; Romano A; ENITEC
[Ad] Endereço:Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands; Department of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, The Netherlands.
[Ti] Título:High mRNA levels of 17ß-hydroxysteroid dehydrogenase type 1 correlate with poor prognosis in endometrial cancer.
[So] Source:Mol Cell Endocrinol;442:51-57, 2017 Feb 15.
[Is] ISSN:1872-8057
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Most endometrial cancers (ECs) are diagnosed at an early stage and have a good prognosis. However, 20-30% develop recurrence and have poor survival. Recurrence-risk prediction at diagnosis is hampered by the scarcity of prognostic markers. Most ECs are estrogen related, and recent studies show that estrogen exposure in EC is controlled intracrinally. We aim at assessing any association between patient prognosis and the pathways controlling the intracrine estrogen generation in EC: (a) the balance between 17ß-hydroxysteroid-dehydrogenase-type 1 (HSD17B1), that generates active estrogens, and HSD17B2, converting active into poorly active compounds; (b) the balance between steroid sulphatase (STS, that activates estrogens) and estrogen-sulphotransferase (SULT1E1, that deactivates estrogens); (c) the levels of aromatase (ARO), that converts androgen into estrogens. mRNA levels of HSD17B1, HSD17B2, STS, SULT1E1 and ARO were determined among 175 ECs using cDNA microarray. Proteins were explored by immunohistochemistry. Patients with high mRNA of HSD17B1 had a poorer prognosis compared with those with low levels. Combining the expression of HSD17B1 and HSD17B2, patients with high tumour expression of HSD17B1 and low levels of HSD17B2 had the poorest prognosis. Contrarily, women that had high tumour levels of HSD17B2 and low of HSD17B1 had the best outcome. No differences were seen between mRNA level of other the genes analysed and prognosis. At the protein level, HSD17B2, STS and SULT1E1 were highly expressed, whereas HSD17B1 was low and ARO was almost absent. In conclusion, HSD17B1 is a promising marker to predict EC prognosis. Immunohistochemical detection of this protein in ECs has low sensitivity and should be improved for future clinical applications.
[Mh] Termos MeSH primário: Neoplasias do Endométrio/metabolismo
Neoplasias do Endométrio/patologia
Estradiol Desidrogenases/metabolismo
RNA Mensageiro/metabolismo
[Mh] Termos MeSH secundário: Idoso
Aromatase/metabolismo
Biomarcadores Tumorais/metabolismo
Estrogênios/metabolismo
Feminino
Seres Humanos
Recidiva Local de Neoplasia
Prognóstico
Esteril-Sulfatase/metabolismo
Sulfotransferases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Estrogens); 0 (RNA, Messenger); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.1.1.62 (HSD17B1 protein, human); EC 1.1.1.62 (HSD17B2 protein, human); EC 1.14.14.1 (Aromatase); EC 2.8.2.- (Sulfotransferases); EC 2.8.2.4 (estrone sulfotransferase); EC 3.1.6.2 (Steryl-Sulfatase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161208
[St] Status:MEDLINE


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[PMID]:27531568
[Au] Autor:Sánchez-Guijo A; Neunzig J; Gerber A; Oji V; Hartmann MF; Schuppe HC; Traupe H; Bernhardt R; Wudy SA
[Ad] Endereço:Steroid Research & Mass Spectrometry Unit, Division of Pediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Feulgenstrasse 12, 35392, Giessen, Germany. Electronic address: alberto.sanchezguijo@uni-giessen.de.
[Ti] Título:Role of steroid sulfatase in steroid homeostasis and characterization of the sulfated steroid pathway: Evidence from steroid sulfatase deficiency.
[So] Source:Mol Cell Endocrinol;437:142-153, 2016 Dec 05.
[Is] ISSN:1872-8057
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:The impact of steroid sulfatase (STS) activity in the circulating levels of both sulfated and unconjugated steroids is only partially known. In addition, the sulfated steroid pathway, a parallel pathway to the one for unconjugated steroids, which uses the same enzymes, has never been characterized in detail before. Patients with steroid sulfatase deficiency (STSD) are unable to enzymatically convert sulfated steroids into their unconjugated forms, and are a good model to elucidate how STS affects steroid biosynthesis and to study the metabolism of sulfated steroids. We quantified unconjugated and sulfated steroids in STSD serum, and compared these results with data obtained from serum of healthy controls. Most sulfated steroids were increased in STSD. However, androstenediol-3-sulfate and epiandrosterone sulfate showed similar levels in both groups, and the concentrations of androsterone sulfate were notably lower. Hydroxylated forms of DHEAS and of pregnenolone sulfate were found to be increased in STSD, suggesting a mechanism to improve the excretion of sulfated steroids. STSD testosterone concentrations were normal, but cholesterol and DHEA were significantly decreased. Additionally, serum bile acids were three-fold higher in STSD. Correlations between concentrations of steroids in each group indicate that 17α-hydroxy-pregnenolone-3-sulfate in men is mainly biosynthesized from the precursor pregnenolone sulfate and androstenediol-3-sulfate from DHEAS. These findings confirm the coexistence of two steroidogenic pathways: one for unconjugated steroids and another one for sulfated steroids. Each pathway is responsible for the synthesis of specific steroids. The equal levels of testosterone, and the reduced level of unconjugated precursors in STSD, support that testosterone is primarily synthesized from sulfated steroids. In consequence, testosterone synthesis in STSD relies on an enzyme with sulfatase activity other than STS. This study reveals that STS is a key player of steroid biosynthesis regulating the availability of circulating cholesterol.
[Mh] Termos MeSH primário: Homeostase
Ictiose Ligada ao Cromossomo X/metabolismo
Ictiose Ligada ao Cromossomo X/patologia
Esteroides/metabolismo
Esteril-Sulfatase/metabolismo
Sulfatos/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Estudos de Casos e Controles
Criança
Pré-Escolar
Desidroepiandrosterona
Estradiol Desidrogenases/metabolismo
Seres Humanos
Meia-Idade
Pregnenolona
Esteroide 17-alfa-Hidroxilase/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Steroids); 0 (Sulfates); 04Y4D91RG0 (pregnenolone sulfate); 459AG36T1B (Dehydroepiandrosterone); 73R90F7MQ8 (Pregnenolone); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.1.1.62 (HSD17B2 protein, human); EC 1.14.14.19 (CYP17A1 protein, human); EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase); EC 3.1.6.2 (Steryl-Sulfatase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160818
[St] Status:MEDLINE


  10 / 440 MEDLINE  
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[PMID]:27424610
[Au] Autor:Herman BE; Szabó J; Bacsa I; Wölfling J; Schneider G; Bálint M; Hetényi C; Mernyák E; Szécsi M
[Ad] Endereço:a 1st Department of Medicine, University of Szeged , Szeged , Hungary.
[Ti] Título:Comparative investigation of the in vitro inhibitory potencies of 13-epimeric estrones and D-secoestrones towards 17ß-hydroxysteroid dehydrogenase type 1.
[So] Source:J Enzyme Inhib Med Chem;31(sup3):61-69, 2016.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The inhibitory effects of 13-epimeric estrones, D-secooxime and D-secoalcohol estrone compounds on human placental 17ß-hydroxysteroid dehydrogenase type 1 isozyme (17ß-HSD1) were investigated. The transformation of estrone to 17ß-estradiol was studied by an in vitro radiosubstrate incubation method. 13α-Estrone inhibited the enzyme activity effectively with an IC value of 1.2 µM, which indicates that enzyme affinity is similar to that of the natural estrone substrate. The 13ß derivatives and the compounds bearing a 3-hydroxy group generally exerted stronger inhibition than the 13α and 3-ether counterparts. The 3-hydroxy-13ß-D-secoalcohol and the 3-hydroxy-13α-D-secooxime displayed an outstanding cofactor dependence, i.e. more efficient inhibition in the presence of NADH than NADPH. The 3-hydroxy-13ß-D-secooxime has an IC value of 0.070 µM and is one of the most effective 17ß-HSD1 inhibitors reported to date in the literature.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Estradiol Desidrogenases/antagonistas & inibidores
Estrona/análogos & derivados
Estrona/farmacologia
[Mh] Termos MeSH secundário: Citosol/efeitos dos fármacos
Citosol/enzimologia
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Estradiol Desidrogenases/metabolismo
Estrona/química
Seres Humanos
Conformação Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 2DI9HA706A (Estrone); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.1.1.62 (HSD17B1 protein, human)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170223
[Lr] Data última revisão:
170223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160719
[St] Status:MEDLINE



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