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Estrogen and Related Compounds: Biphasic Dose Responses 

Author: Edward J. Calabrese a
Affiliation:   a Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003 USA. Tel: 413-545-3164. Fax: 413-545-4692. email: edwardc@schoolph.umass.edu.
DOI: 10.1080/20014091111785
Publication Frequency: 10 issues per year
Published in: journal Critical Reviews in Toxicology, Volume 31, Issue 4 & 5 July 2001 , pages 503 - 515
Subject: Toxicology;
Formats available: PDF (English)
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Abstract

This article documents and quantitatively assesses the capacity of estrogen, phytoestrogens, and antiestrogens to affect biphasic dose-response relationships in animal/human models and across a broad range of cell types, affecting multiple endpoints. The range of endpoints displaying such biphasic dose responses includes plasminogen activation, oxytocin secretion, angiogenesis, cell proliferation, bone growth, monocyte chemotaxis, secretion of various cytokines, and other effects. The quantitative features of the dose response relationships revealed that the magnitude of the stimulatory responses was typically less than twofold, whereas the stimulatory responses were markedly variable ranging from about 5- to 106fold. Mechanistic explanations of the biphasic responses are addressed.
Keywords: estrogen; phytoestrogen; antiestrogen; testosterone; plasminogen; hormesis; U shaped; biphasic; stimulatory; inhibitory; dose response; receptor mediated
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