Differential regulation of dopamine transporter function and location by low concentrations of environmental estrogens and 17β-estradiol

Rebecca A. Alyea, Cheryl S. Watson

    Research output: Contribution to journalArticle

    39 Citations (Scopus)

    Abstract

    Background: The effects of 17β-estradiol(E2) and xenoestrogens (XEs) on dopamine transport may have important implications for the increased incidence of neurologic disorders, especially in women during life stages characterized by frequent hormonal fluctuations. Objective: We examined low concentrations of XEs [dieldrin, endosulfan, o'p'-dichlorodiphenyl-ethylene (DDE), nonylphenol (NP), and bisphenol A (BPA)] for nongenomic actions via action of membrane estrogen receptors (ERs). Methods: We measured activity of the dopamine transporter (DAT) by the efflux of 3H-dopamine in nontransfected nerve growth factor-differentiated PC12 rat pheochromocytoma cells expressing membrane DAT, ER-α, ER-β, and G-protein-coupled receptor 30. We used a plate immunoassay to monitor trafficking of these proteins. Results: All compounds at 1 nM either caused efflux or inhibited efflux, or both; each compound evoked a distinct oscillatory pattern. At optimal times for each effect, we examined different concentrations of XEs. All XEs were active at some concentration < 10 nM, and dose responses were all nonmonotonic. For example, 10-14 to 10-11 M DDE caused significant efflux inhibition, whereas NP and BPA enhanced or inhibited efflux at several concentrations. We also measured the effects of E2/XE combinations; DDE potentiated E2-mediated dopamine efflux, whereas BPA inhibited it. In E2-induced efflux, 15% more ER-α trafficked to the membrane, whereas ER-β waned; during BPA-induced efflux, 20% more DAT was trafficked to the plasma membrane. Conclusions: Low levels of environmental estrogen contaminants acting as endocrine disruptors via membrane ERs can alter dopamine efflux temporal patterning and the trafficking of DAT and membrane ERs, providing a cellular mechanism that could explain the disruption of physiologic neurotransmitter function.

    Original languageEnglish (US)
    Pages (from-to)778-783
    Number of pages6
    JournalEnvironmental Health Perspectives
    Volume117
    Issue number5
    DOIs
    StatePublished - 2009

    Fingerprint

    Dopamine Plasma Membrane Transport Proteins
    Estrogen Receptors
    Estradiol
    Estrogens
    Dopamine
    Membranes
    Cell Membrane
    Endosulfan
    Dieldrin
    Endocrine Disruptors
    Membrane Transport Proteins
    Pheochromocytoma
    Nerve Growth Factor
    Protein Transport
    G-Protein-Coupled Receptors
    Nervous System Diseases
    Immunoassay
    Neurotransmitter Agents
    bisphenol A
    Incidence

    Keywords

    • Dopamine efflux
    • Low concentrations
    • Nongenomic
    • Xenoestrogens

    ASJC Scopus subject areas

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

    Cite this

    Differential regulation of dopamine transporter function and location by low concentrations of environmental estrogens and 17β-estradiol. / Alyea, Rebecca A.; Watson, Cheryl S.

    In: Environmental Health Perspectives, Vol. 117, No. 5, 2009, p. 778-783.

    Research output: Contribution to journalArticle

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    abstract = "Background: The effects of 17β-estradiol(E2) and xenoestrogens (XEs) on dopamine transport may have important implications for the increased incidence of neurologic disorders, especially in women during life stages characterized by frequent hormonal fluctuations. Objective: We examined low concentrations of XEs [dieldrin, endosulfan, o'p'-dichlorodiphenyl-ethylene (DDE), nonylphenol (NP), and bisphenol A (BPA)] for nongenomic actions via action of membrane estrogen receptors (ERs). Methods: We measured activity of the dopamine transporter (DAT) by the efflux of 3H-dopamine in nontransfected nerve growth factor-differentiated PC12 rat pheochromocytoma cells expressing membrane DAT, ER-α, ER-β, and G-protein-coupled receptor 30. We used a plate immunoassay to monitor trafficking of these proteins. Results: All compounds at 1 nM either caused efflux or inhibited efflux, or both; each compound evoked a distinct oscillatory pattern. At optimal times for each effect, we examined different concentrations of XEs. All XEs were active at some concentration < 10 nM, and dose responses were all nonmonotonic. For example, 10-14 to 10-11 M DDE caused significant efflux inhibition, whereas NP and BPA enhanced or inhibited efflux at several concentrations. We also measured the effects of E2/XE combinations; DDE potentiated E2-mediated dopamine efflux, whereas BPA inhibited it. In E2-induced efflux, 15{\%} more ER-α trafficked to the membrane, whereas ER-β waned; during BPA-induced efflux, 20{\%} more DAT was trafficked to the plasma membrane. Conclusions: Low levels of environmental estrogen contaminants acting as endocrine disruptors via membrane ERs can alter dopamine efflux temporal patterning and the trafficking of DAT and membrane ERs, providing a cellular mechanism that could explain the disruption of physiologic neurotransmitter function.",
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    N2 - Background: The effects of 17β-estradiol(E2) and xenoestrogens (XEs) on dopamine transport may have important implications for the increased incidence of neurologic disorders, especially in women during life stages characterized by frequent hormonal fluctuations. Objective: We examined low concentrations of XEs [dieldrin, endosulfan, o'p'-dichlorodiphenyl-ethylene (DDE), nonylphenol (NP), and bisphenol A (BPA)] for nongenomic actions via action of membrane estrogen receptors (ERs). Methods: We measured activity of the dopamine transporter (DAT) by the efflux of 3H-dopamine in nontransfected nerve growth factor-differentiated PC12 rat pheochromocytoma cells expressing membrane DAT, ER-α, ER-β, and G-protein-coupled receptor 30. We used a plate immunoassay to monitor trafficking of these proteins. Results: All compounds at 1 nM either caused efflux or inhibited efflux, or both; each compound evoked a distinct oscillatory pattern. At optimal times for each effect, we examined different concentrations of XEs. All XEs were active at some concentration < 10 nM, and dose responses were all nonmonotonic. For example, 10-14 to 10-11 M DDE caused significant efflux inhibition, whereas NP and BPA enhanced or inhibited efflux at several concentrations. We also measured the effects of E2/XE combinations; DDE potentiated E2-mediated dopamine efflux, whereas BPA inhibited it. In E2-induced efflux, 15% more ER-α trafficked to the membrane, whereas ER-β waned; during BPA-induced efflux, 20% more DAT was trafficked to the plasma membrane. Conclusions: Low levels of environmental estrogen contaminants acting as endocrine disruptors via membrane ERs can alter dopamine efflux temporal patterning and the trafficking of DAT and membrane ERs, providing a cellular mechanism that could explain the disruption of physiologic neurotransmitter function.

    AB - Background: The effects of 17β-estradiol(E2) and xenoestrogens (XEs) on dopamine transport may have important implications for the increased incidence of neurologic disorders, especially in women during life stages characterized by frequent hormonal fluctuations. Objective: We examined low concentrations of XEs [dieldrin, endosulfan, o'p'-dichlorodiphenyl-ethylene (DDE), nonylphenol (NP), and bisphenol A (BPA)] for nongenomic actions via action of membrane estrogen receptors (ERs). Methods: We measured activity of the dopamine transporter (DAT) by the efflux of 3H-dopamine in nontransfected nerve growth factor-differentiated PC12 rat pheochromocytoma cells expressing membrane DAT, ER-α, ER-β, and G-protein-coupled receptor 30. We used a plate immunoassay to monitor trafficking of these proteins. Results: All compounds at 1 nM either caused efflux or inhibited efflux, or both; each compound evoked a distinct oscillatory pattern. At optimal times for each effect, we examined different concentrations of XEs. All XEs were active at some concentration < 10 nM, and dose responses were all nonmonotonic. For example, 10-14 to 10-11 M DDE caused significant efflux inhibition, whereas NP and BPA enhanced or inhibited efflux at several concentrations. We also measured the effects of E2/XE combinations; DDE potentiated E2-mediated dopamine efflux, whereas BPA inhibited it. In E2-induced efflux, 15% more ER-α trafficked to the membrane, whereas ER-β waned; during BPA-induced efflux, 20% more DAT was trafficked to the plasma membrane. Conclusions: Low levels of environmental estrogen contaminants acting as endocrine disruptors via membrane ERs can alter dopamine efflux temporal patterning and the trafficking of DAT and membrane ERs, providing a cellular mechanism that could explain the disruption of physiologic neurotransmitter function.

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    KW - Xenoestrogens

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