Abstract
Bisphenol-A (BPA) is one of the highest-volume chemicals produced worldwide and the widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Its estrogenic activity has been well documented in the last 15 years. In addition to estrogen receptors, BPA has been also shown to bind to and activate the estrogen-related receptor γ and pregnane X receptor and inhibit the androgen receptor. Halogenated BPAs were also shown to activate the peroxisome proliferator-activated receptor γ and inhibit thyroid hormone receptors. In this chapter, we review recent studies shedding light on the structural and molecular mechanisms by which BPA and its halogenated derivatives interfere with nuclear hormone receptor signaling. These data provide guidelines for the development of safer substitutes devoid of hormonal activity and may help environmental risk assessment.
Keywords:
Bisphenol-A; Endocrine disruptor; Halogenated bisphenol-A; Nuclear hormone receptor.
© 2014 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Androgen Antagonists / chemistry
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Androgen Antagonists / toxicity*
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Animals
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Benzhydryl Compounds / chemistry
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Benzhydryl Compounds / toxicity*
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Endocrine Disruptors / chemistry
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Endocrine Disruptors / toxicity
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Environmental Pollutants / chemistry
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Environmental Pollutants / toxicity*
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Estrogens, Non-Steroidal / chemistry
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Estrogens, Non-Steroidal / toxicity*
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Halogenation
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Humans
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PPAR gamma / agonists*
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PPAR gamma / metabolism
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Phenols / chemistry
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Phenols / toxicity*
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Pregnane X Receptor
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Receptors, Androgen / chemistry
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Receptors, Androgen / metabolism
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Receptors, Estrogen / agonists
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Receptors, Estrogen / metabolism
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Receptors, Steroid / agonists*
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Receptors, Steroid / metabolism
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Receptors, Thyroid Hormone / antagonists & inhibitors*
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Receptors, Thyroid Hormone / metabolism
Substances
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Androgen Antagonists
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Benzhydryl Compounds
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Endocrine Disruptors
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Environmental Pollutants
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Estrogens, Non-Steroidal
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PPAR gamma
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Phenols
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Pregnane X Receptor
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Receptors, Androgen
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Receptors, Estrogen
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Receptors, Steroid
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Receptors, Thyroid Hormone
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bisphenol A