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

40 Scopus citations

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 - Jun 9 2009

Keywords

  • Dopamine efflux
  • Low concentrations
  • Nongenomic
  • Xenoestrogens

ASJC Scopus subject areas

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

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