Neurological diseases including Parkinson's, Tourette's, attention deficit hyperactivity disorder (ADHD), Alzheimer's, and schizophrenia are all associated with alterations in dopamine-driven function involving the dopamine transporter (DAT).
Research published in the open access journal BMC Neuroscience suggests that a number of estrogens acting through their receptors affect the DAT, which may explain trends in timing of women's susceptibility to these diseases.
Rebecca Alyea and Cheryl Watson from the University of Texas Medical Branch investigated how physiological estrogen levels might influence neurochemical pathways including dopamine signalling. The authors tested the rapid nongenomic effects of several physiological estrogens (estradiol, estrone, and estriol) on dopamine efflux via the DAT in a non-transfected rat neuronal cell culture model that expresses the three membrane estrogen receptors ERα, ERß, and GPR30.
The authors found that estradiol-mediated dopamine efflux is DAT-specific and not dependent on extracellular Ca2+-mediated vesicular release of dopamine. Using kinase inhibitors they also showed that estradiol-mediated dopamine efflux is dependent on specific signaling kinases (protein kinase C and MEK, but not on PI3K or protein kinase A). While inhibiting dopamine efflux, estrone and estriol caused DAT to leave the plasma membrane.