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5.
J Steroid Biochem Mol Biol ; 155(Pt B): 217-23, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24816231

RESUMO

This introductory chapter provides an overview of the levels and sites at which endocrine disruptors (EDs) affect steroid actions. In contrast to the special issue of Journal of Steroid Biochemistry and Molecular Biology published three years ago and devoted to EDs as such, this paper focuses on steroids. We tried to point to more recent findings and opened questions. EDs interfere with steroid biosynthesis and metabolism either as inhibitors of relevant enzymes, or at the level of their expression. Particular attention was paid to enzymes metabolizing steroid hormones to biologically active products in target cells, such as aromatase, 5α-reductase and 3ß-, 11ß- and 17ß-hydroxysteroid dehydrogenases. An important target for EDs is also steroid acute regulatory protein (StAR), responsible for steroid precursor trafficking to mitochondria. EDs influence receptor-mediated steroid actions at both genomic and non-genomic levels. The remarkable differences in response to various steroid-receptor ligands led to a more detailed investigation of events following steroid/disruptor binding to the receptors and to the mapping of the signaling cascades and nuclear factors involved. A virtual screening of a large array of EDs with steroid receptors, known as in silico methods (≡computer simulation), is another promising approach for studying quantitative structure activity relationships and docking. New data may be expected on the effect of EDs on steroid hormone binding to selective plasma transport proteins, namely transcortin and sex hormone-binding globulin. Little information is available so far on the effects of EDs on the major hypothalamo-pituitary-adrenal/gonadal axes, of which the kisspeptin/GPR54 system is of particular importance. Kisspeptins act as stimulators for hormone-induced gonadotropin secretion and their expression is regulated by sex steroids via a feed-back mechanism. Kisspeptin is now believed to be one of the key factors triggering puberty in mammals, and various EDs affect its expression and function. Finally, advances in analytics of EDs, especially those persisting in the environment, in various body fluids (plasma, urine, seminal fluid, and follicular fluid) are mentioned. Surprisingly, relatively scarce information is available on the simultaneous determination of EDs and steroids in the same biological material. This article is part of a Special Issue entitled 'Endocrine disruptors & steroids'.


Assuntos
Disruptores Endócrinos/farmacologia , Hormônios Esteroides Gonadais/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , 17-Hidroxiesteroide Desidrogenases/genética , 17-Hidroxiesteroide Desidrogenases/metabolismo , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Disruptores Endócrinos/história , Regulação da Expressão Gênica , Hormônios Esteroides Gonadais/história , Ensaios de Triagem em Larga Escala , História do Século XX , História do Século XXI , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Simulação de Acoplamento Molecular , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Globulina de Ligação a Hormônio Sexual/genética , Globulina de Ligação a Hormônio Sexual/metabolismo , Transdução de Sinais , Relação Estrutura-Atividade , Transcortina/genética , Transcortina/metabolismo
8.
Am J Public Health ; 99 Suppl 3: S559-66, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19890158

RESUMO

Bisphenol A (BPA), a synthetic chemical used in the production of plastics since the 1950s and a known endocrine disruptor, is a ubiquitous component of the material environment and human body. New research on very-low-dose exposure to BPA suggests an association with adverse health effects, including breast and prostate cancer, obesity, neurobehavioral problems, and reproductive abnormalities. These findings challenge the long-standing scientific and legal presumption of BPA's safety. The history of how BPA's safety was defined and defended provides critical insight into the questions now facing lawmakers and regulators: is BPA safe, and if not, what steps must be taken to protect the public's health? Answers to both questions involve reforms in chemical policy, with implications beyond BPA.


Assuntos
Exposição Ocupacional/legislação & jurisprudência , Saúde Ocupacional , Fenóis/efeitos adversos , Plásticos/efeitos adversos , Poluentes Ocupacionais do Ar , Compostos Benzidrílicos , Testes de Carcinogenicidade , Relação Dose-Resposta a Droga , Disruptores Endócrinos/administração & dosagem , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/história , Regulamentação Governamental , História do Século XX , História do Século XXI , Humanos , Fenóis/administração & dosagem , Fenóis/história , Plásticos/história , Política , Estados Unidos , United States Environmental Protection Agency , United States Food and Drug Administration
9.
PLoS Biol ; 5(7): e193, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17594178
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