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 language | English (US) |
|---|---|
| Pages (from-to) | 778-783 |
| Number of pages | 6 |
| Journal | Environmental Health Perspectives |
| Volume | 117 |
| Issue number | 5 |
| DOIs | |
| State | Published - 2009 |
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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 journal › Article
}
TY - JOUR
T1 - Differential regulation of dopamine transporter function and location by low concentrations of environmental estrogens and 17β-estradiol
AU - Alyea, Rebecca A.
AU - Watson, Cheryl S.
PY - 2009
Y1 - 2009
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.
KW - Dopamine efflux
KW - Low concentrations
KW - Nongenomic
KW - Xenoestrogens
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U2 - 10.1289/ehp.0800026
DO - 10.1289/ehp.0800026
M3 - Article
VL - 117
SP - 778
EP - 783
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
SN - 0091-6765
IS - 5
ER -