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

Abstract

Estrogen receptor alpha (ER alpha) and ER beta 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 ER beta-selective antibody that cross-reacts with mouse, rat, and human ER beta protein and its use to determine the distribution of ER beta in the murine brain. Further, a previously characterized polyclonal antibody to ER alpha was used to compare the distribution of the two receptors in the first comprehensive description of ER distribution specifically in the mouse brain. ER beta 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 ER alpha-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 ER beta and ER alpha 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.

Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

“…Indeed, estrogen receptors regulate taurine uptake via the Na þ -dependent taurine transporter (TauT) in MCF-7 human breast cancer cells (Han et al, 2006;Shennan and Thomson, 2007). Both estrogen receptors ERa and ERb are present in the mouse cortex, hippocampus, and striatum, although striatal levels of either messenger RNA or protein are much lower (Küppers and Beyer, 1999;Mitra et al, 2003;Shughrue and Merchenthaler, 2000). Estrogen receptors modulate brain function and, like taurine, afford neuroprotection in the cortex and hippocampus (Shughrue and Merchenthaler, 2000).…”

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

“…Using ER-null mice several reports described the selective involvement of ERa in the anti-inflammatory and neuroprotective activity of estradiol against neuroinflammatory and vascular pathologies of the brain ( [62,80,185,242]). Despite the fact that ERb has been shown to be expressed widely in the CNS in adult mice ( [161,167]), it appears that this receptor isoform is not involved in mediating the protective effect of estrogens in neuroinflammatory diseases. Yet, both ERa and ERb are involved in the control of inflammation by estradiol, depending on the tissue involved and on the signal utilized [88].…”

Differential Effects of Estrogen Receptor Alpha and Beta Specific Agonists on Social Learning of Food Preferences in Female Mice

“…In mice, ERb is highly expressed in the parahippocampal region, predominant in the diagonal band of Broca, and in the hippocampus proper (Mitra et al, 2003;Merchenthaler et al, 2004), all areas which have been implicated in memory of the STFP (Alvarez et al, 2002;Vale-Martinez et al, 2002). This suggests that the facilitatory effects of WAY-200070 could be through some of the mechanisms that have been described for estradiol (for a review, see McEwen, 2002), and that some of the actions of estradiol on these mechanisms are through ERb.…”