Sex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains

Abstract Background ESR2, a nuclear estrogen receptor also known as estrogen receptor β, is expressed in the brain and contributes to the actions of estrogen in various physiological phenomena. However, its expression profiles in the brain have long been debated because of difficulties in detecting...

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Main Authors: Masahiro Morishita, Shimpei Higo, Kinuyo Iwata, Hirotaka Ishii
Format: Article
Language:English
Published: BMC 2023-12-01
Series:Biology of Sex Differences
Subjects:
Online Access:https://doi.org/10.1186/s13293-023-00574-z
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author Masahiro Morishita
Shimpei Higo
Kinuyo Iwata
Hirotaka Ishii
author_facet Masahiro Morishita
Shimpei Higo
Kinuyo Iwata
Hirotaka Ishii
author_sort Masahiro Morishita
collection DOAJ
description Abstract Background ESR2, a nuclear estrogen receptor also known as estrogen receptor β, is expressed in the brain and contributes to the actions of estrogen in various physiological phenomena. However, its expression profiles in the brain have long been debated because of difficulties in detecting ESR2-expressing cells. In the present study, we aimed to determine the distribution of ESR2 in rodent brains, as well as its sex and interspecies differences, using immunohistochemical detection with a well-validated anti-ESR2 antibody (PPZ0506). Methods To determine the expression profiles of ESR2 protein in rodent brains, whole brain sections from mice and rats of both sexes were subjected to immunostaining for ESR2. In addition, to evaluate the effects of circulating estrogen on ESR2 expression profiles, ovariectomized female mice and rats were treated with low or high doses of estrogen, and the resulting numbers of ESR2-immunopositive cells were analyzed. Welch’s t-test was used for comparisons between two groups for sex differences, and one-way analysis of variance followed by the Tukey–Kramer test were used for comparisons among multiple groups with different estrogen treatments. Results ESR2-immunopositive cells were observed in several subregions of mouse and rat brains, including the preoptic area, extended amygdala, hypothalamus, mesencephalon, and cerebral cortex. Their distribution profiles exhibited sex and interspecies differences. In addition, low-dose estrogen treatment in ovariectomized female mice and rats tended to increase the numbers of ESR2-immunopositive cells, whereas high-dose estrogen treatment tended to decrease these numbers. Conclusions Immunohistochemistry using the well-validated PPZ0506 antibody revealed a more localized expression of ESR2 protein in rodent brains than has previously been reported. Furthermore, there were marked sex and interspecies differences in its distribution. Our histological analyses also revealed estrogen-dependent changes in ESR2 expression levels in female brains. These findings will be helpful for understanding the ESR2-mediated actions of estrogen in the brain.
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spelling doaj.art-773326235c7f4aa5b650994fb00a57412023-12-24T12:08:15ZengBMCBiology of Sex Differences2042-64102023-12-0114111810.1186/s13293-023-00574-zSex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brainsMasahiro Morishita0Shimpei Higo1Kinuyo Iwata2Hirotaka Ishii3Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical SchoolDepartment of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical SchoolDepartment of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical SchoolDepartment of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical SchoolAbstract Background ESR2, a nuclear estrogen receptor also known as estrogen receptor β, is expressed in the brain and contributes to the actions of estrogen in various physiological phenomena. However, its expression profiles in the brain have long been debated because of difficulties in detecting ESR2-expressing cells. In the present study, we aimed to determine the distribution of ESR2 in rodent brains, as well as its sex and interspecies differences, using immunohistochemical detection with a well-validated anti-ESR2 antibody (PPZ0506). Methods To determine the expression profiles of ESR2 protein in rodent brains, whole brain sections from mice and rats of both sexes were subjected to immunostaining for ESR2. In addition, to evaluate the effects of circulating estrogen on ESR2 expression profiles, ovariectomized female mice and rats were treated with low or high doses of estrogen, and the resulting numbers of ESR2-immunopositive cells were analyzed. Welch’s t-test was used for comparisons between two groups for sex differences, and one-way analysis of variance followed by the Tukey–Kramer test were used for comparisons among multiple groups with different estrogen treatments. Results ESR2-immunopositive cells were observed in several subregions of mouse and rat brains, including the preoptic area, extended amygdala, hypothalamus, mesencephalon, and cerebral cortex. Their distribution profiles exhibited sex and interspecies differences. In addition, low-dose estrogen treatment in ovariectomized female mice and rats tended to increase the numbers of ESR2-immunopositive cells, whereas high-dose estrogen treatment tended to decrease these numbers. Conclusions Immunohistochemistry using the well-validated PPZ0506 antibody revealed a more localized expression of ESR2 protein in rodent brains than has previously been reported. Furthermore, there were marked sex and interspecies differences in its distribution. Our histological analyses also revealed estrogen-dependent changes in ESR2 expression levels in female brains. These findings will be helpful for understanding the ESR2-mediated actions of estrogen in the brain.https://doi.org/10.1186/s13293-023-00574-zMouseRatBrainEstrogenESR2ERβ
spellingShingle Masahiro Morishita
Shimpei Higo
Kinuyo Iwata
Hirotaka Ishii
Sex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains
Biology of Sex Differences
Mouse
Rat
Brain
Estrogen
ESR2
ERβ
title Sex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains
title_full Sex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains
title_fullStr Sex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains
title_full_unstemmed Sex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains
title_short Sex and interspecies differences in ESR2-expressing cell distributions in mouse and rat brains
title_sort sex and interspecies differences in esr2 expressing cell distributions in mouse and rat brains
topic Mouse
Rat
Brain
Estrogen
ESR2
ERβ
url https://doi.org/10.1186/s13293-023-00574-z
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AT shimpeihigo sexandinterspeciesdifferencesinesr2expressingcelldistributionsinmouseandratbrains
AT kinuyoiwata sexandinterspeciesdifferencesinesr2expressingcelldistributionsinmouseandratbrains
AT hirotakaishii sexandinterspeciesdifferencesinesr2expressingcelldistributionsinmouseandratbrains