Cited by 95Estrogen and related hormone effectsNeuroendocrine regulation and behaviorNeuroscience and Neuropharmacology Research

Oestrogen Receptor α Localisation in the Prefrontal Cortex of Three Mammalian Species

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Montague, D., Weickert, C. S., Tomaskovic‐Crook, E., Rothmond, D. A., Kleinman, J. E., Rubinow, D. R.·2008·Journal of Neuroendocrinology

Abstract

Oestrogen modulates cognitive function and affective behaviours subserved by the prefrontal cortex (PFC). Identifying and localising oestrogen receptor (ER)alpha, in human PFC will contribute to our understanding of the molecular mechanism of oestrogen action in this region. Inferences about the site of action of oestrogen in human brain are derived largely from studies performed in nonhuman mammalian species; however, the congruence of findings across species has not been demonstrated. Furthermore, the laminar, cellular, and subcellular localisation of ERalpha in the cortex is debated. Therefore, we compared the distribution of ERalpha in human dorsolateral prefrontal cortex (DLPFC) with that of monkey DLPFC and rat medial PFC. Immunohistochemistry performed on frontal cortex from the three species demonstrated ERalpha positive cells throughout all layers of the PFC, in pyramidal and nonpyramidal neurones, with both nuclear and cytoplasmic immunoreactivity. Western blot analyses and preabsorption studies confirmed that the antibody used recognised ERalpha and not ERbeta. A strong ERalpha immunoreactive band corresponding to the full-length ERalpha protein (65-67 kDa) in the frontal cortex of all three species matched the size of the predominant immunoreactive band detected in breast cancer cell lines known to express ERalpha. Additionally, other ERalpha immunoreactive proteins of varying molecular weight in breast cancer cells, rat ovary and mammalian brain were detected, suggesting that ERalpha may exist in more than one form in the mammalian frontal cortex. The present study provides evidence that ERalpha protein exists in neurones in mammalian PFC and that ERalpha is anatomically well-positioned to directly mediate oestrogen action in these neurones.

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  1. Shughrue PJ, Stumpf WE, MacLusky NJ, Zielinski JE, Hochberg RB. Devel- opmental changes in estrogen receptors in mouse cerebral cortex between birth and postweaning: studied by autoradiography with 11 beta-methoxy-16 alpha-[125I]iodoestradiol. Endocrinology 1990; 126: 1112-1124.
  2. Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous sys- tem. J Comp Neurol 1997; 388: 507-525.
  3. Bevitt DJ, Milton ID, Piggot N, Henry L, Carter MJ, Toms GL, Lennard TW, Westley B, Angus B, Horne CH. New monoclonal antibodies to oestrogen and progesterone receptors effective for paraffin section immunohisto- chemistry. J Pathol 1997; 183: 228-232.
  4. Milner TA, McEwen BS, Hayashi S, Li CJ, Reagan LP, Alves SE. Ultrastruc- tural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites. J Comp Neurol 2001; 429: 355-371.

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Authors
Montague, D., Weickert, C. S., Tomaskovic‐Crook, E., Rothmond, D. A., Kleinman, J. E., & Rubinow, D. R.
Affiliations
  • National Institutes of Health (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Weickert, C. S.
Venue
Journal of Neuroendocrinology
Publisher
Wiley
Published
2008-07
Volume
20
Issue
7
Pages
893-903
ISSN
  • 0953-8194 (ISSN-L)
  • 1365-2826
OpenAlex
W2051071393
Cited by
95
References
51
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 8 · 2016: 9 · 2015: 7 · 2014: 10 · 2013: 4 · 2012: 11
FWCI
2.85
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • Research Online (University of Wollongong) (submittedVersion)
  • UNC Libraries
Funders
  • National Alliance for Research on Schizophrenia and Depression
  • National Institutes of Health
  • National Institute of Mental Health (Z01MH002399, Z01MH002864)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
estrogen receptor alpha, prefrontal cortex, dorsolateral prefrontal cortex, medial prefrontal cortex, species comparison, subcellular localization
MeSH terms
Adult, Animals, Autopsy, Brain Chemistry, Humans, Macaca mulatta, Male, Mammals, Middle Aged, Models, Biological, Neurons, Tissue Distribution, Rats, Sprague-Dawley, Prefrontal Cortex, Estrogen Receptor alpha, Rats

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