Distribution of estrogen receptor beta mRNA-containing cells in ovariectomized and estrogen-treated female rat brain

Abstract

Estrogen receptor (ER)-beta is a member of the nuclear receptor superfamily and mediates various estrogenic actions. Changes in ER-alpha mRNA expression induced by estrogen have been well documented, whereas those with regard to ER-beta have only been reported for a part of the hypothalamus. In the present study, we examined the effect of estrogen on ER-beta mRNA expression in the female rat brain. Detection of ER-beta mRNA using the in situ hybridization method with a digoxigenin-labeled RNA probe was performed in two groups of female rats: ovariectomized (OVX) and estrogen (E2)-treated. A wide distribution of ER-beta mRNA-containing cells was demonstrated in both groups. In the E2-treated group compared with the OVX group, the number of ER-beta mRNA-containing cells was significantly reduced in the external plexiform layer of the olfactory bulb, entorhinal cortex, intermediate part of the lateral septal nucleus, nucleus of the horizontal limb of the diagonal band, amygdala (lateral, medial and basolateral part), thalamus (anteroventral, laterodorsal and lateral posterior part), medial geniculate nucleus, suprachiasmatic nucleus and Purkinje cells in the cerebellum. These results reveal that ER-beta mRNA-containing cells were decreased by estrogen in several brain regions in the female rat brain, suggesting that ER-beta mRNA is downregulated by the physiological level of estrogen in a region-specific manner.

Age-related changes in the expression of ER-β mRNA in the female rat brain

“…Similar to those studies (Shughrue et al, 1996(Shughrue et al, , 1997(Shughrue et al, , 1998Hrabovszky et al, 1998;Price Jr. and Handa, 2000;Shima et al, 2003), we detected ER-β mRNA with abundance in brain areas including the olfactory bulb, hippocampus, amygdala, and supraoptic and paraventricular nuclei of the hypothalamus. Wilson et al (2002) examined the effects of aging on ER-β mRNA expression in the cortex, preoptic area, paraventricular hypothalamic nucleus and supraoptic nucleus, and detected decreases in only the cortex and supraoptic nucleus in ovariectomized aged rats compared with young rats.…”

“…The hormonal influences on cognitive processes appear to involve actions on the hippocampus and basal forebrain (McEwen and Alves, 1999). ER-β mRNA is distributed in hippocampal and cerebral cortical regions that contain little or no ER-α (Shughrue et al, 1997;Li et al, 1997;Shima et al, 2003), implying the possibility that estrogen is involved in cognitive function through activating ER-β. Moreover, the decline in receptor expression may correlate with the cognitive decline seen in aged humans and rodents (Wilson et al, 2002).…”

“…Preparation of probes and in situ hybridization were performed as described previously (Shima et al, 2003). Briefly, a 391-bp (bases 1-391) ER-β complementary RNA probe corresponding to an EcoRI-AccI fragment of ER-β was used for in situ hybridization (Kuiper et al, 1996).…”

“…In the rat brain, ER-β mRNA is distributed widely, in a pattern different from that of ER-α mRNA (Shughrue et al, 1997;Shima et al, 2003). Both ER-α and ER-β mRNA are abundant in the same brain regions: the preoptic area, bed nucleus of the stria terminalis and medial amygdala (Simerly et al, 1990;Shughrue et al, 1997).…”

“…In addition, in vitro studies have shown that ER-β can form heterodimers with ER-α (Cowley et al, 1997;Pace et al, 1997;Pettersson et al, 1997;Ogawa et al, 1998;Matsuda et al, 2002), 5 suggesting that estrogen may differentially modulate the activity of certain neuronal populations depending on whether the cells express ER-α, ER-β or both (Shughrue et al, 1998). ER-β mRNA is also highly distributed in several rat brain regions, including the olfactory bulb, cerebral cortex, paraventricular hypothalamic nucleus, supraoptic nucleus, hippocampus and cerebellar Purkinje cells, areas that contain little or no ER-α mRNA (Simerly et al, 1990;Shughrue et al, 1997;Mufson et al, 1999;Shima et al, 2003;Mehra et al, 2005). The differences in the distribution patterns of ER-α and ER-β suggest different physiological roles of each receptor subtype in the central nervous system.…”