Abstract
Estrogen receptor (ER)-β is a member of the nuclear receptor superfamily and mediates various estrogenic actions. Changes in ER-α mRNA expression induced by estrogen have been well documented, whereas those with regard to ER-β have only been reported for a part of the hypothalamus. In the present study, we examined the effect of estrogen on ER-β mRNA expression in the female rat brain. Detection of ER-β 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-β mRNA-containing cells was demonstrated in both groups. In the E2-treated group compared with the OVX group, the number of ER-β 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-β mRNA-containing cells were decreased by estrogen in several brain regions in the female rat brain, suggesting that ER-β mRNA is downregulated by the physiological level of estrogen in a region-specific manner.
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Brown TJ, Scherz B, Hochberg RB, MacLusky NJ (1996) Regulation of estrogen receptor concentrations in the rat brain: Effects of sustained androgen and estrogen exposure. Neuroendocrinology 63, 53–60.
Butcher RL, Collins WE, Fugo NW (1974) Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17β throughout the 4-day estrous cycle of the rat. Endocrinology 94, 1704–8.
Cowley SM, Hoare S, Mosselman S, Parker MG (1997) Estrogen receptors α and β form heterodimers on DNA. J Biol Chem 272, 19 858–62.
Hrabovszky E, Kalló I, Hajszán T, Shughrue PJ, Merchenthaler I, Liposits Z (1998) Expression of estrogen receptor-b messenger ribonucleic acid in oxytocin and vasopressin neurons of the rat supraoptic and paraventricular nuclei. Endocrinology 139, 2600–4.
Hrabovszky E, Steinhauser A, Barab SK et al. (2000) Estrogen receptor-β immunoreactivity in luteinizing hormone-releasing hormone neurons of the rat brain. Endocrinology 142, 3261–4.
Jakab RL, Wong JK, Belcher SM (2001) Estrogen receptor beta immunoreactivity in differentiating cells of the developing rat cerebellum. J Comp Neurol 430, 396–409.
Koch M (1990) Effects of Treatment with estradiol and parental experience on the number and distribution of estrogen-binding neurons in the ovariectomized mouse brain. Neuroendocrinology 51, 505–14.
Koch M, Ehret G (1989) Immunocytochemical localization and quantitation of estrogen-binding cells in the male and female (virgin, pregnant, lactating) mouse brain. Brain Res 489, 101–12.
Krege JH, Hodgin JB, Couse JF et al. (1998) Generation and reproductive phenotypes of mice lacking estrogen receptor β. Proc Natl Acad Sci USA 95, 15 677–82.
Kuiper GGJM, Carlsson B, Grandien K et al. (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptor α and β. Endocrinology 138, 863–70.
Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J-Å (1996) Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93, 5925–30.
Lauber AH, Mobbs CV, Muramatsu M, Pfaff DW (1991) Estrogen receptor messenger RNA expression in rat hypothalamus as a function of genetic sex and estrogen dose. Endocrinology 129, 3180–6.
Legan SJ, Coon GA, Karsch FJ (1975) Role of estrogen as initiator of daily LH surges in the ovariectomized rat. Endocrinology 96, 50–6.
Lubahn DB, Moyer JS, Goldin TS, Couse JF, Korach KS, Smithies O (1993) Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci USA 90, 11 162–6.
Mufson EJ, Cai WJ, Jaffar S et al. (1999) Estrogen receptor immunoreactivity within subregions of the rat forebrain: Neuronal distribution and association with perikarya containing choline acetyltransferase. Brain Res 849, 253–74.
Ogawa S, Chan J, Chester AE, Gustafsson J-Å, Korach KS, Pfaff DW (1999) Survival of reproductive behaviors in estrogen receptor β gene-deficient (βERKO) male and female mice. Proc Natl Acad Sci USA 96, 12 887–92.
Ogawa S, Inoue S, Watanabe T et al. (1998) The complete primary structure of human estrogen receptor β (hERβ) and its heterodimerization with ERα in vivo and in vitro. Biochem Biophysics Res Commun 243, 122–6.
Ogawa S, Taylor JA, Lubahn DB, Korach KS, Pfaff DW (1996) Reversal of sex roles in genetic female mice by disruption of estrogen receptor gene. Neuroendocrinology 64, 467–70.
Orikasa C, Kondo Y, Hayashi S, McEwen BS, Sakuma Y (2002) Sexually dimorphic expression of estrogen receptor β in the anteroventral periventricular nucleus of the rat preoptic area: Implication in luteinizing hormone surge. Proc Natl Acad Sci USA 99, 3306–11.
Orikasa C, McEwen BS, Hayashi H, Sakuma Y, Hayashi S (2000) Estrogen receptor alpha, but not beta, is expressed in the interneurons of the hippocampus in prepubertal rats: An in situ hybridization study. Dev Brain Res 120, 245–54.
Österlund M, Kuiper GGJM, Gustafsson J-Å, Hurd YL (1998) Differential distribution and regulation of estrogen receptor-α and -β mRNA within the female rat brain. Mol Brain Res 54, 175–80.
Pace P, Taylor J, Suntharalingam S, Coombes RC, Ali S (1997) Human estrogen receptor β binds DNA in a manner similar to and dimerizes with estrogen receptor α. J Biol Chem 272, 25 832–8.
Pasterkamp RJ, Yuri K, Morita N, Kawata M (1997) Differential expression of estrogen receptor mRNA and protein in the female rat preoptic area. Neurosci Lett 239, 81–4.
Patisaul HB, Whitten PL, Young LJ (1999) Regulation of estrogen receptor beta mRNA in the brain: Opposite effects of 17β-estradiol and the phytoestrogen, coumestrol. Mol Brain Res 67, 165–71.
Paxinos G, Watson C (1998) The Rat Brain in Stereotaxic Coordinates. Academic Press, New York.
Pettersson K, Grandien K, Kuiper GGJM, Gustafsson J-Å (1997) Mouse estrogen receptor β forms estrogen response elementbinding heterodimers with estrogen receptor α. Mol Endocrinol 11, 1486–96.
Pettersson K, Gustafsson J-Å (2001) Role of estrogen receptor beta in estrogen action. Annu Rev Physiol 63, 165–92.
Price Jr RH, Handa RJ (2000) Expression of estrogen receptorbeta protein and mRNA in the cerebellum of the rat. Neurosci Lett 288, 115–8.
Rissman EF, Wersinger SR, Fugger HN, Foster TC (1999) Sex with knockout models: Behavioral studies of estrogen receptor α. Brain Res 835, 80–90.
Shughrue PJ, Komm B, Merchenthaler I (1996) The distribution of estrogen receptor-β mRNA in the rat hypothalamus. Steroids 61, 678–81.
Shughrue PJ, Lane MV, Merchenthaler I (1997) Comparative distribution of estrogen receptor-α and-β mRNA in the rat central nervous system. J Comp Neurol 388, 507–25.
Shughrue PJ, Merchenthaler I (2001) Distribution of estrogen receptor β immunoreactivity in the rat central nervous system. J Comp Neurol 436, 64–81.
Shughrue PJ, Scrimo PJ, Merchenthaler I (1998) Evidence for the colocalization of estrogen receptor-β mRNA and estrogen receptor-α immunoreactivity in neurons of the rat forebrain. Endocrinology 139, 5267–70.
Shupnik MA, Gordon MS, Chin WW (1989) Tissue-specific regulation of rat estrogen receptor mRNAs. Mol Endocrinol 3, 660–5.
Simerly RB, Chang C, Muramatsu M, Swanson LW (1990) Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: An in situ hybridization study. J Comp Neurol 294, 76–95.
Simerly RB, Young BJ (1991) Regulation of estrogen receptor messenger ribonucleic acid in rat hypothalamus by sex steroid hormones. Mol Endocrinol 5, 424–32.
Simpson ER (1998) Genetic mutations resulting in estrogen insufficiency in the male. Mol Cell Endocrinol 145, 55–9.
Wang L, Andersson S, Warner M, Gustafsson J-Å (2001) Morphological abnormalities in the brains of estrogen receptor β knockout mice. Proc Natl Acad Sci USA 98, 2792–6.
Yuri K, Kawata M (1991) The effect of estrogen on the estrogen receptor-immunoreactive cells in the rat medial preoptic nucleus. Brain Res 548, 50–4.
Zhang J-Q, Cai W-Q, Zhou D-S, Su B-Y (2002) Distribution and differences of estrogen receptor beta immunoreactivity in the brain of adult male and female rats. Brain Res 935, 73–80.
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Shima, N., Yamaguchi, Y. & Yuri, K. Distribution of estrogen receptor β mRNA-containing cells in ovariectomized and estrogen-treated female rat brain. Anato Sci Int 78, 85–97 (2003). https://doi.org/10.1046/j.0022-7722.2003.00042.x
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DOI: https://doi.org/10.1046/j.0022-7722.2003.00042.x