Combinations of physiologic estrogens with xenoestrogens alter ERK phosphorylation profiles in rat pituitary cells

Yow Jiun Jeng, Cheryl S. Watson

    Research output: Contribution to journalArticle

    38 Citations (Scopus)

    Abstract

    Background: Estrogens are potent non genomic phospho-activators of extracellular-signal- regulated kinases (ERKs). A major concern about the toxicity of xenoestrogens (XEs) is potential alteration of responses to physiologic estrogens when XEs are present simultaneously. objectives: We examined estrogen-induced ERK activation, comparing the abilities of structurally related XEs (alkylphenols and bisphenol A) to alter ERK responses induced by physiologic concentrations (1 nM) of estradiol (E2), estrone (E1), and estriol (E3). Methods: We quantified hormone/mimetic-induced ERK phosphorylations in the GH3/B6/F10 rat pituitary cell line using a plate immuno assay, comparing effects with those on cell proliferation and by estrogen receptor subtype-selective ligands. results: Alone, these structurally related XEs activate ERKs in an oscillating temporal pattern similar (but not identical) to that with physiologic estrogens. Te potency of all estrogens was similar (active between femtomolar and nanomolar concentrations). XEs potently disrupted physiologic estrogen signaling at low, environmentally relevant concentrations. Generally, XEs potentiated (at the lowest, subpicomolar concentrations) and attenuated (at the highest, picomolar to 100 nM concentrations) the actions of the physiologic estrogens. Some XEs showed pronounced non monotonic responses/inhibitions. Te phosphorylated ERK and proliferative responses to receptor-selective ligands were only partially correlated. conclusions: XEs are both imperfect potent estrogens and endocrine disruptors; the more efca-cious an XE, the more it disrupts actions of physiologic estrogens. Tis ability to disrupt physiologic estrogen signaling suggests that XEs may disturb normal functioning at life stages where actions of particular estrogens are important (e.g., development, reproductive cycling, pregnancy, menopause).

    Original languageEnglish (US)
    Pages (from-to)104-113
    Number of pages10
    JournalEnvironmental Health Perspectives
    Volume119
    Issue number1
    DOIs
    StatePublished - Jan 2011

    Fingerprint

    Extracellular Signal-Regulated MAP Kinases
    Estrogens
    Phosphorylation
    Ligands
    Endocrine Disruptors
    Estriol
    Estrone
    Menopause
    Estrogen Receptors
    Estradiol
    Cell Proliferation
    Hormones
    Cell Line
    Pregnancy

    Keywords

    • ERα
    • ERβ
    • ERK activation
    • GPER
    • Membrane estrogen receptors
    • Non genomic effects
    • Physiologic estrogens
    • Prolactinoma cell line
    • Xenoestrogens

    ASJC Scopus subject areas

    • Health, Toxicology and Mutagenesis
    • Public Health, Environmental and Occupational Health

    Cite this

    Combinations of physiologic estrogens with xenoestrogens alter ERK phosphorylation profiles in rat pituitary cells. / Jeng, Yow Jiun; Watson, Cheryl S.

    In: Environmental Health Perspectives, Vol. 119, No. 1, 01.2011, p. 104-113.

    Research output: Contribution to journalArticle

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    abstract = "Background: Estrogens are potent non genomic phospho-activators of extracellular-signal- regulated kinases (ERKs). A major concern about the toxicity of xenoestrogens (XEs) is potential alteration of responses to physiologic estrogens when XEs are present simultaneously. objectives: We examined estrogen-induced ERK activation, comparing the abilities of structurally related XEs (alkylphenols and bisphenol A) to alter ERK responses induced by physiologic concentrations (1 nM) of estradiol (E2), estrone (E1), and estriol (E3). Methods: We quantified hormone/mimetic-induced ERK phosphorylations in the GH3/B6/F10 rat pituitary cell line using a plate immuno assay, comparing effects with those on cell proliferation and by estrogen receptor subtype-selective ligands. results: Alone, these structurally related XEs activate ERKs in an oscillating temporal pattern similar (but not identical) to that with physiologic estrogens. Te potency of all estrogens was similar (active between femtomolar and nanomolar concentrations). XEs potently disrupted physiologic estrogen signaling at low, environmentally relevant concentrations. Generally, XEs potentiated (at the lowest, subpicomolar concentrations) and attenuated (at the highest, picomolar to 100 nM concentrations) the actions of the physiologic estrogens. Some XEs showed pronounced non monotonic responses/inhibitions. Te phosphorylated ERK and proliferative responses to receptor-selective ligands were only partially correlated. conclusions: XEs are both imperfect potent estrogens and endocrine disruptors; the more efca-cious an XE, the more it disrupts actions of physiologic estrogens. Tis ability to disrupt physiologic estrogen signaling suggests that XEs may disturb normal functioning at life stages where actions of particular estrogens are important (e.g., development, reproductive cycling, pregnancy, menopause).",
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    N2 - Background: Estrogens are potent non genomic phospho-activators of extracellular-signal- regulated kinases (ERKs). A major concern about the toxicity of xenoestrogens (XEs) is potential alteration of responses to physiologic estrogens when XEs are present simultaneously. objectives: We examined estrogen-induced ERK activation, comparing the abilities of structurally related XEs (alkylphenols and bisphenol A) to alter ERK responses induced by physiologic concentrations (1 nM) of estradiol (E2), estrone (E1), and estriol (E3). Methods: We quantified hormone/mimetic-induced ERK phosphorylations in the GH3/B6/F10 rat pituitary cell line using a plate immuno assay, comparing effects with those on cell proliferation and by estrogen receptor subtype-selective ligands. results: Alone, these structurally related XEs activate ERKs in an oscillating temporal pattern similar (but not identical) to that with physiologic estrogens. Te potency of all estrogens was similar (active between femtomolar and nanomolar concentrations). XEs potently disrupted physiologic estrogen signaling at low, environmentally relevant concentrations. Generally, XEs potentiated (at the lowest, subpicomolar concentrations) and attenuated (at the highest, picomolar to 100 nM concentrations) the actions of the physiologic estrogens. Some XEs showed pronounced non monotonic responses/inhibitions. Te phosphorylated ERK and proliferative responses to receptor-selective ligands were only partially correlated. conclusions: XEs are both imperfect potent estrogens and endocrine disruptors; the more efca-cious an XE, the more it disrupts actions of physiologic estrogens. Tis ability to disrupt physiologic estrogen signaling suggests that XEs may disturb normal functioning at life stages where actions of particular estrogens are important (e.g., development, reproductive cycling, pregnancy, menopause).

    AB - Background: Estrogens are potent non genomic phospho-activators of extracellular-signal- regulated kinases (ERKs). A major concern about the toxicity of xenoestrogens (XEs) is potential alteration of responses to physiologic estrogens when XEs are present simultaneously. objectives: We examined estrogen-induced ERK activation, comparing the abilities of structurally related XEs (alkylphenols and bisphenol A) to alter ERK responses induced by physiologic concentrations (1 nM) of estradiol (E2), estrone (E1), and estriol (E3). Methods: We quantified hormone/mimetic-induced ERK phosphorylations in the GH3/B6/F10 rat pituitary cell line using a plate immuno assay, comparing effects with those on cell proliferation and by estrogen receptor subtype-selective ligands. results: Alone, these structurally related XEs activate ERKs in an oscillating temporal pattern similar (but not identical) to that with physiologic estrogens. Te potency of all estrogens was similar (active between femtomolar and nanomolar concentrations). XEs potently disrupted physiologic estrogen signaling at low, environmentally relevant concentrations. Generally, XEs potentiated (at the lowest, subpicomolar concentrations) and attenuated (at the highest, picomolar to 100 nM concentrations) the actions of the physiologic estrogens. Some XEs showed pronounced non monotonic responses/inhibitions. Te phosphorylated ERK and proliferative responses to receptor-selective ligands were only partially correlated. conclusions: XEs are both imperfect potent estrogens and endocrine disruptors; the more efca-cious an XE, the more it disrupts actions of physiologic estrogens. Tis ability to disrupt physiologic estrogen signaling suggests that XEs may disturb normal functioning at life stages where actions of particular estrogens are important (e.g., development, reproductive cycling, pregnancy, menopause).

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    KW - Prolactinoma cell line

    KW - Xenoestrogens

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