Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.
George G. J. M. Kuiper,J.G. Lemmen,Bo Carlsson,J. Christopher Corton,Stephen Safe,Paul T. van der Saag,Bart van der Burg,Jan-Åke Gustafsson +7 more
TLDR
The estrogenic activity of environmental chemicals and phytoestrogens in competition binding assays with ERα or ERβ protein, and in a transient gene expression assay using cells in which an acute estrogenic response is created by cotransfecting cultures with recombinant human ERβ complementary DNA (cDNA) in the presence of an estrogen-dependent reporter plasmid are investigated.Abstract:
The rat, mouse and human estrogen receptor (ER) exists as two subtypes, ER alpha and ER beta, which differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activity of environmental chemicals and phytoestrogens in competition binding assays with ER alpha or ER beta protein, and in a transient gene expression assay using cells in which an acute estrogenic response is created by cotransfecting cultures with recombinant human ER alpha or ER beta complementary DNA (cDNA) in the presence of an estrogen-dependent reporter plasmid. Saturation ligand-binding analysis of human ER alpha and ER beta protein revealed a single binding component for [3H]-17beta-estradiol (E2) with high affinity [dissociation constant (Kd) = 0.05 - 0.1 nM]. All environmental estrogenic chemicals [polychlorinated hydroxybiphenyls, dichlorodiphenyltrichloroethane (DDT) and derivatives, alkylphenols, bisphenol A, methoxychlor and chlordecone] compete with E2 for binding to both ER subtypes with a similar preference and degree. In most instances the relative binding affinities (RBA) are at least 1000-fold lower than that of E2. Some phytoestrogens such as coumestrol, genistein, apigenin, naringenin, and kaempferol compete stronger with E2 for binding to ER beta than to ER alpha. Estrogenic chemicals, as for instance nonylphenol, bisphenol A, o, p'-DDT and 2',4',6'-trichloro-4-biphenylol stimulate the transcriptional activity of ER alpha and ER beta at concentrations of 100-1000 nM. Phytoestrogens, including genistein, coumestrol and zearalenone stimulate the transcriptional activity of both ER subtypes at concentrations of 1-10 nM. The ranking of the estrogenic potency of phytoestrogens for both ER subtypes in the transactivation assay is different; that is, E2 >> zearalenone = coumestrol > genistein > daidzein > apigenin = phloretin > biochanin A = kaempferol = naringenin > formononetin = ipriflavone = quercetin = chrysin for ER alpha and E2 >> genistein = coumestrol > zearalenone > daidzein > biochanin A = apigenin = kaempferol = naringenin > phloretin = quercetin = ipriflavone = formononetin = chrysin for ER beta. Antiestrogenic activity of the phytoestrogens could not be detected, except for zearalenone which is a full agonist for ER alpha and a mixed agonist-antagonist for ER beta. In summary, while the estrogenic potency of industrial-derived estrogenic chemicals is very limited, the estrogenic potency of phytoestrogens is significant, especially for ER beta, and they may trigger many of the biological responses that are evoked by the physiological estrogens.read more
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Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement
Evanthia Diamanti-Kandarakis,Jean-Pierre Bourguignon,Linda C. Giudice,Russ Hauser,Gail S. Prins,Ana M. Soto,R. Thomas Zoeller,Andrea C. Gore +7 more
TL;DR: The evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology is presented.
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Dietary polyphenols and the prevention of diseases
TL;DR: Experimental studies on animals or cultured human cell lines support a role of polyphenols in the prevention of cardiovascular diseases, cancers, neurodegenerative diseases, diabetes, or osteoporosis, but no clear associations have been found between cancer risk and polyphenol consumption.
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Human exposure to bisphenol A (BPA).
TL;DR: The reported levels of BPA in human fluids are higher than the BPA concentrations reported to stimulate molecular endpoints in vitro and appear to be within an order of magnitude of the levels needed to induce effects in animal models.
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Mechanisms of Estrogen Action
Stefan Nilsson,Sari Mäkelä,Eckardt Treuter,Michel Tujague,Jane S. Thomsen,Göran Andersson,Eva Enmark,Katarina Pettersson,Margaret Warner,Jan-Åke Gustafsson +9 more
TL;DR: The role of estrogen receptors in physiology and pathology has been investigated in the past decade and it was found that there was not one but two distinct and functional estrogen receptors, now called ERα and ERβ.
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The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration
Anne-Simone Parent,Grete Teilmann,Anders Juul,Niels E. Skakkebæk,Jorma Toppari,Jean-Pierre Bourguignon +5 more
TL;DR: These observations urge further study of the onset of puberty as a possible sensitive and early marker of the interactions between environmental conditions and genetic susceptibility that can influence physiological and pathological processes.
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