Estrogen Receptors Are Found in Glia and at Extranuclear Neuronal Sites in the Dorsal Striatum of Female Rats: Evidence for Cholinergic But Not Dopaminergic Colocalization

Estrogens rapidly affect dopamine (DA) neurotransmission in the dorsal striatum (dSTR) and DA-related diseases, such as Parkinson's disease and schizophrenia. How estrogens influence DA function remains unclear, in part, because the ultrastructural localization of estrogen receptors (ER) in the dSTR is not known. Light microscopic studies of the dSTR have suggested the presence of ER. This experiment used electron microscopy to determine whether these ER are at extranuclear sites in the dSTR, providing evidence for a mechanism through which estrogen could rapidly affect DA transmission. The dSTR was labeled with antibodies for ER alpha, ER beta, and G protein-coupled ER 1 (GPER-1) to confirm whether these ER were present in this brain area. After this, the dSTR was dual labeled with antibodies for ER alpha or GPER-1 and tyrosine hydroxylase or vesicular acetylcholine transporter to determine whether ER are localized to dopaminergic and/or cholinergic processes, respectively. Ultrastructural analysis revealed immunoreactivity (IR) for ER alpha, ER beta, and GPER-1 exclusively at extranuclear sites throughout the dSTR. ER alpha-, ER beta-, and GPER-1-IR are mostly frequently observed in axons and glial profiles but are also localized to other neuronal profiles. Dual labeling revealed that ER alpha- and GPER-1-IR is not associated with DA axons and terminals but is sometimes associated with cholinergic neurons. Because these receptors are exclusively extranuclear in the dSTR, binding at these receptors likely affects neurotransmission via nongenomic mechanisms. (Endocrinology 153:5373-5383, 2012)