Cellular and subcellular localization of estrogen and progestin receptor immunoreactivities in the mouse hippocampus

Estrogen receptor‐α (ERα), estrogen receptor‐β (ERβ), and progestin receptor (PR) immunoreactivities are localized to extranuclear sites in the rat hippocampal formation. Because rats and mice respond differently to estradiol treatment at a cellular level, the present study examined the distribution of ovarian hormone receptors in the dorsal hippocampal formation of mice. For this, antibodies to ERα, ERβ, and PR were localized by light and electron immunomicroscopy in male and female mice across the estrous cycle. Light microscopic examination of the mouse hippocampal formation showed sparse nuclear ERα and PR immunoreactivity (‐ir) most prominently in the CA1 region and diffuse ERβ‐ir primarily in the CA1 pyramidal cell layer as well as in a few interneurons. Ultrastructural analysis additionally revealed discrete extranuclear ERα‐, ERβ‐, and PR‐ir in neuronal and glial profiles throughout the hippocampal formation. Although extranuclear profiles were detected in all animal groups examined, the amount and types of profiles varied with sex and estrous cycle phase. ERα‐ir was highest in diestrus females, particularly in dendritic spines, axons, and glia. Similarly, ERβ‐ir was highest in estrus and diestrus females, mainly in dendritic spines and glia. Conversely, PR‐ir was highest during proestrus, mostly in axons. Except for very low levels of extranuclear ERβ‐ir in mossy fiber terminals in mice, the labeling patterns in the mice for all three antibodies were similar to the ultrastructural labeling found previously in rats, suggesting that regulation of these receptors is well conserved across the two species. J. Comp. Neurol. 518:2729–2743, 2010. © 2010 Wiley‐Liss, Inc.