Immunolocalization of Estrogen Receptor β in the Mouse Brain: Comparison with Estrogen Receptor α

TLDR

Estrogen receptors α and β are steroid nuclear receptors that regulate gene transcription and have been identified in both peripheral tissues and the central nervous system, with most prior data derived from rats. The study aimed to develop an ERβ‑selective antibody and use it to map ERβ distribution in the mouse brain, comparing it with ERα. The authors generated a cross‑reactive ERβ antibody for mouse, rat, and human, and employed a previously characterized ERα polyclonal antibody to perform comparative immunohistochemical mapping of both receptors in the mouse brain. ERβ immunoreactivity was largely nuclear in discrete brain regions such as the olfactory bulb, cortex, septum, and various hypothalamic nuclei, with some extranuclear staining, and although both receptors were broadly expressed, ERα predominated in the hippocampus, preoptic area, and most hypothalamus while ERβ was more prominent elsewhere, establishing a region‑selective expression pattern that underpins estrogen’s neural actions.

Abstract

Estrogen receptor α (ERα) and ERβ are members of the steroid nuclear receptor family that modulate gene transcription in an estrogen-dependent manner. ER mRNA and protein have been detected both peripherally and in the central nervous system, with most data having come from the rat. Here we report the development of an ERβ-selective antibody that cross-reacts with mouse, rat, and human ERβ protein and its use to determine the distribution of ERβ in the murine brain. Further, a previously characterized polyclonal antibody to ERα was used to compare the distribution of the two receptors in the first comprehensive description of ER distribution specifically in the mouse brain. ERβ immunoreactivity (ir) was primarily localized to cell nuclei within select regions of the brain, including the olfactory bulb, cerebral cortex, septum, preoptic area, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamic nucleus, thalamus, ventral tegmental area, substantia nigra, dorsal raphe, locus coeruleus, and cerebellum. Extranuclear-ir was detected in several areas, including fibers of the olfactory bulb, CA3 stratum lucidum, and CA1 stratum radiatum of the hippocampus and cerebellum. Although both receptors were generally expressed in a similar distribution through the brain, nuclear ERα-ir was the predominant subtype in the hippocampus, preoptic area, and most of the hypothalamus, whereas it was sparse or absent from the cerebral cortex and cerebellum. Collectively, these findings demonstrate the region-selective expression of ERβ and ERα in the adult ovariectomized mouse brain. These data provide an anatomical framework for understanding the mechanisms by which estrogen regulates specific neural systems in the mouse.