Rapid estrogenic signaling activities of modified (chlorinated, sulfonated, and glucuronidated) endocrine disruptor bisphenol A

Rene Vinas, Randall Goldblum, Cheryl Watson

Research output: Contribution to journalArticle

Abstract

An automated in-vitro, medium-throughput screening method was designed to compare the rapid actions of 10−9M estradiol to those of modified bisphenol A (BPA) compounds: chlorinated (created due to waste water treatment) and phase II BPA metabolites. GH3/B6/F10 prolactinoma cells were treated with increasing concentrations (10−15‒10−7M) of BPA or modified BPA compounds for 5 min, and phospho-activated kinases assayed via a fixed-cell plate immunoassay. Mono- and di-chlorinated BPAs phospho-activated the extracellular signal-regulated kinase (ERK), while tri-chlorinated BPA dephosphorylated ERK to a level below vehicle-treated controls. When c-Jun-N-terminal kinase (JNK) was examined, mono-chlorinated compounds caused no responses (similar to unmodified BPA), while di- and tri-chlorinated BPAs caused extensive dephosphorylation. When deconjugation of di-sulfated and glucuronidated metabolites were inhibited, these stably conjugated compounds were unable to activate either ERK or JNK, but could inactivate them. This suggests that the modified versions of BPA (extensively chlorinated or conjugated metabolites) may alter the ability of membrane estrogen receptor-α (which mediates these rapid signaling responses) to partner with other signaling proteins. While other studies have examined the estrogenicity of modified (chlorinated and conjugated) BPA compounds in gene expression assays, this is the first to examine their actions via rapid, membrane-initiated signaling pathways.
Original languageEnglish (US)
JournalEndocrine Disruptors
DOIs
StatePublished - 2013

Fingerprint

Endocrine Disruptors
Extracellular Signal-Regulated MAP Kinases
Phosphotransferases
Prolactinoma
Membranes
bisphenol A
JNK Mitogen-Activated Protein Kinases
Water Purification
Waste Water
Immunoassay
Estrogen Receptors
Estradiol
Gene Expression

Keywords

  • phosphorylated
  • non-monotonic
  • polychlorinated
  • non-genomic
  • estradiol
  • membrane estrogen receptor

Cite this

Rapid estrogenic signaling activities of modified (chlorinated, sulfonated, and glucuronidated) endocrine disruptor bisphenol A. / Vinas, Rene; Goldblum, Randall; Watson, Cheryl.

In: Endocrine Disruptors, 2013.

Research output: Contribution to journalArticle

@article{7054e13328ca431b95eb843c2144cd50,
title = "Rapid estrogenic signaling activities of modified (chlorinated, sulfonated, and glucuronidated) endocrine disruptor bisphenol A",
abstract = "An automated in-vitro, medium-throughput screening method was designed to compare the rapid actions of 10−9M estradiol to those of modified bisphenol A (BPA) compounds: chlorinated (created due to waste water treatment) and phase II BPA metabolites. GH3/B6/F10 prolactinoma cells were treated with increasing concentrations (10−15‒10−7M) of BPA or modified BPA compounds for 5 min, and phospho-activated kinases assayed via a fixed-cell plate immunoassay. Mono- and di-chlorinated BPAs phospho-activated the extracellular signal-regulated kinase (ERK), while tri-chlorinated BPA dephosphorylated ERK to a level below vehicle-treated controls. When c-Jun-N-terminal kinase (JNK) was examined, mono-chlorinated compounds caused no responses (similar to unmodified BPA), while di- and tri-chlorinated BPAs caused extensive dephosphorylation. When deconjugation of di-sulfated and glucuronidated metabolites were inhibited, these stably conjugated compounds were unable to activate either ERK or JNK, but could inactivate them. This suggests that the modified versions of BPA (extensively chlorinated or conjugated metabolites) may alter the ability of membrane estrogen receptor-α (which mediates these rapid signaling responses) to partner with other signaling proteins. While other studies have examined the estrogenicity of modified (chlorinated and conjugated) BPA compounds in gene expression assays, this is the first to examine their actions via rapid, membrane-initiated signaling pathways.",
keywords = "phosphorylated, non-monotonic, polychlorinated, non-genomic, estradiol, membrane estrogen receptor",
author = "Rene Vinas and Randall Goldblum and Cheryl Watson",
year = "2013",
doi = "10.4161/endo.25411",
language = "English (US)",
journal = "Endocrine Disruptors",
publisher = "Taylor and Francis AS",

}

TY - JOUR

T1 - Rapid estrogenic signaling activities of modified (chlorinated, sulfonated, and glucuronidated) endocrine disruptor bisphenol A

AU - Vinas, Rene

AU - Goldblum, Randall

AU - Watson, Cheryl

PY - 2013

Y1 - 2013

N2 - An automated in-vitro, medium-throughput screening method was designed to compare the rapid actions of 10−9M estradiol to those of modified bisphenol A (BPA) compounds: chlorinated (created due to waste water treatment) and phase II BPA metabolites. GH3/B6/F10 prolactinoma cells were treated with increasing concentrations (10−15‒10−7M) of BPA or modified BPA compounds for 5 min, and phospho-activated kinases assayed via a fixed-cell plate immunoassay. Mono- and di-chlorinated BPAs phospho-activated the extracellular signal-regulated kinase (ERK), while tri-chlorinated BPA dephosphorylated ERK to a level below vehicle-treated controls. When c-Jun-N-terminal kinase (JNK) was examined, mono-chlorinated compounds caused no responses (similar to unmodified BPA), while di- and tri-chlorinated BPAs caused extensive dephosphorylation. When deconjugation of di-sulfated and glucuronidated metabolites were inhibited, these stably conjugated compounds were unable to activate either ERK or JNK, but could inactivate them. This suggests that the modified versions of BPA (extensively chlorinated or conjugated metabolites) may alter the ability of membrane estrogen receptor-α (which mediates these rapid signaling responses) to partner with other signaling proteins. While other studies have examined the estrogenicity of modified (chlorinated and conjugated) BPA compounds in gene expression assays, this is the first to examine their actions via rapid, membrane-initiated signaling pathways.

AB - An automated in-vitro, medium-throughput screening method was designed to compare the rapid actions of 10−9M estradiol to those of modified bisphenol A (BPA) compounds: chlorinated (created due to waste water treatment) and phase II BPA metabolites. GH3/B6/F10 prolactinoma cells were treated with increasing concentrations (10−15‒10−7M) of BPA or modified BPA compounds for 5 min, and phospho-activated kinases assayed via a fixed-cell plate immunoassay. Mono- and di-chlorinated BPAs phospho-activated the extracellular signal-regulated kinase (ERK), while tri-chlorinated BPA dephosphorylated ERK to a level below vehicle-treated controls. When c-Jun-N-terminal kinase (JNK) was examined, mono-chlorinated compounds caused no responses (similar to unmodified BPA), while di- and tri-chlorinated BPAs caused extensive dephosphorylation. When deconjugation of di-sulfated and glucuronidated metabolites were inhibited, these stably conjugated compounds were unable to activate either ERK or JNK, but could inactivate them. This suggests that the modified versions of BPA (extensively chlorinated or conjugated metabolites) may alter the ability of membrane estrogen receptor-α (which mediates these rapid signaling responses) to partner with other signaling proteins. While other studies have examined the estrogenicity of modified (chlorinated and conjugated) BPA compounds in gene expression assays, this is the first to examine their actions via rapid, membrane-initiated signaling pathways.

KW - phosphorylated

KW - non-monotonic

KW - polychlorinated

KW - non-genomic

KW - estradiol

KW - membrane estrogen receptor

U2 - 10.4161/endo.25411

DO - 10.4161/endo.25411

M3 - Article

JO - Endocrine Disruptors

JF - Endocrine Disruptors

ER -