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Behavioral, biochemical and anatomical studies suggest that estrogen stimulates structure and/or function in the adult cerebral cortex. The studies presented here used immunocytochemistry to map the α and β isoforms of intracellular estrogen receptors (ERα, ERβ) in major subdivisions of adult rat cortex to identify potential sites for relevant receptor-mediated hormone actions. These studies revealed that immunoreactivity for ERα (ERα-IR) and ERβ (ERβ-IR) was present in most cortical areas, was associated exclusively with neurons, and was similar in males and females. Each receptor isoform also had its own unique distribution with respect to cortical regions, layers, and cells. In sensorimotor areas, for example, ERβ-IR was more prominent than ERα-IR, and was concentrated in layer V neurons that were immunoreactive for parvalbumin. In contrast, ERα-IR was scattered among parvalbumin-immunonegative cells in layers II/III and V/VI. Likewise, in entorhinal cortex, ERβ-IR was present in calbindin-containing cells in layers III–VI, while ERα-IR was restricted to small numbers of calbindin-negative neurons in infragranular layers. In sum, ERβ-IR and ERα-IR were differentially distributed both with respect to cortical compartments and with respect to each other. Accordingly, estrogen activation at these two sites may be anticipated to impact disparate sets of cortical circuits, cells, and functions.

cerebral cortex

Regional, Laminar, and Cellular Distribution of Immunoreactivity for ERα and ERβ in the Cerebral Cortex of Hormonally Intact, Adult Male and Female Rats