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Estrogen Receptor-β Immunoreactivity in Luteinizing Hormone-Releasing Hormone Neurons of the Rat Brain
Abstract
Feedback regulation of luteinizing hormone-releasing hormone (LHRH) neurons by estradiol plays important roles in the neuroendocrine control of reproduction. Recently, we found that the majority of LHRH neurons in the rat contain estrogen receptor-beta (ER-beta) mRNA, whereas, they seemed to lack ER-alpha mRNA expression. In addition, we observed nuclear uptake of (125)I-estrogen by a subset of these cells. These data suggest that ER-beta is the chief receptor isoform mediating direct estrogen effects upon LHRH neurons. To verify the translation of ER-beta protein within LHRH cells, the present studies applied dual-label immunocytochemistry (ICC) to free-floating sections obtained from the preoptic area of rats. The improved ICC method using the silver-gold intensification of nickel-diaminobenzidine chromogen, enabled the observation of nuclear ER-beta-immunoreactivity in the majority of LHRH cells. The incidence of ER-beta expression was similarly high in LHRH neurons of ovariectomized female (87.8 +/- 2.3%, mean +/- SEM), estradiol-primed female (74.9 +/- 3.2%) and intact male (85.0 +/- 4.7%) rats. The presence of ER-beta mRNA, ER-beta immunoreactivity and (125)I-estrogen binding sites in LHRH neurons of the rat provide strong support for the notion that these cells are directly regulated by estradiol, through ER-beta. The gene targets and molecular mechanisms of this regulation remain unknown.
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“Some studies using immunohistochemistry in rat brain have indeed shown the presence of ERβ in GnRH neuron (Butler, Sjoberg, & Coen, 1999; Hrabovszky et al., 2007; Hrabovszky et al., 2001; Kallo, Butler, Barkovics-Kallo, Goubillon, & Coen, 2001; Navarro et al., 2003; Roy, Angelini, & Belsham, 1999).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Hrabovszky et al., 2001
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Oyola, M. G., & Handa, R. J. (2017) · Stress · doi:10.1080/10253890.2017.1369523 · Cited by 710
“Some studies using immunohistochemistry in rat brain have indeed shown the presence of ERb in GnRH neuron (Butler, Sjoberg, & Coen, 1999; Hrabovszky et al., 2007; Hrabovszky et al., 2001; Kallo, Butler, Barkovics-Kallo, Goubillon, & Coen, 2001; Navarro et al., 2003; Roy, Angelini, & Belsham, 1999).”
BackgroundSmith, J. T., Clay, C. M., Caraty, A., & Clarke, I. J. (2007) · Endocrinology · doi:10.1210/en.2006-1435 · Cited by 404
Rance, N. E., Dacks, P. A., Mittelman-Smith, M. A., Romanovsky, A. A., & Krajewski-Hall, S. J. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.07.003 · Cited by 380
Neurokinin B and the hypothalamic regulation of reproduction
Rance, N. E., Krajewski, S. J., Smith, M. A., Cholanian, M., & Dacks, P. A. (2010) · Brain Research · doi:10.1016/j.brainres.2010.08.059 · Cited by 203
Handa, R. J., Pak, T. R., Kudwa, A. E., Lund, T. D., & Hinds, L. (2008) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.09.012 · Cited by 205
Metadata
- Authors
- Hrabovszky, E., Steinhauser, A., Barabás, K., Shughrue, P. J., Petersen, S. L., Merchenthaler, I., & Liposits, Z.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Department of Neurobiology (E.H., A.S., K.B., Z.S.L.) Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083 Hungary
- The Women’s Health Research Institute (P.J.S., I.M.), Wyeth-Ayerst Research, Radnor, Pennsylvania 19087
- University of Massachusetts Amherst (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2001-07-01
- Volume
- 142
- Issue
- 7
- Pages
- 3261-3264
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2024788152
- Cited by
- 258
- References
- 0
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 10 · 2012: 13
- FWCI
- 18.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-27305)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Keywords
- estrogen receptor beta, luteinizing hormone-releasing hormone neurons, preoptic area, neuroendocrine regulation of reproduction, estrogen binding sites, ovariectomy
- MeSH terms
- Animals, Brain, Estradiol, Female, Immunohistochemistry, Gonadotropin-Releasing Hormone, Male, Neurons, Ovariectomy, Receptors, Estrogen, RNA, Messenger, Rats, Wistar, In Situ Hybridization, Estrogen Receptor beta, Rats
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- CoChat. (2026). Citation check: Estrogen Receptor-β Immunoreactivity in Luteinizing Hormone-Releasing Hormone Neurons of the Rat Brain. https://app.cochat.ai/papers/10.1210/endo.142.7.8176
- The paper
- Hrabovszky, E., Steinhauser, A., Barabás, K., Shughrue, P. J., Petersen, S. L., Merchenthaler, I., & Liposits, Z. (2001). Estrogen Receptor-β Immunoreactivity in Luteinizing Hormone-Releasing Hormone Neurons of the Rat Brain. Endocrinology. https://doi.org/10.1210/endo.142.7.8176