Sex differences in androgen and estrogen receptor expression in rat substantia nigra during development: An immunohistochemical study

T. Ravizza; A. S. Galanopoulou; J. Velíšková; S. L. Moshé

doi:10.1016/S0306-4522(02)00491-8

Sex differences in androgen and estrogen receptor expression in rat substantia nigra during development: An immunohistochemical study

T. Ravizza, A. S. Galanopoulou, J. Velíšková, S. L. Moshé

Neurology

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

Abstract

Gonadal hormones are important regulators of sexual differentiation of the CNS. Exposure to testosterone and estrogen during development causes permanent organizational differences between males and females. We previously described functional sex-related differences of the GABA_Aergic circuits of the rat substantia nigra pars reticulata (SNR) involved in the control of flurothyl seizures. This sexual differentiation of the SNR is regulated by postnatal testosterone. To assess whether the organizing effects of testosterone in the SNR are mediated via the androgen receptor (AR) and/or estrogen receptors (ER), we used immunohistochemistry to study the ontogeny of AR, ERα and ERβ expression in SNR and substantia nigra pars compacta (SNC) of male and female rats. Rats on the day of birth [postnatal day (PN) 0] and at PN1, PN5, PN15 and PN30 were used. AR- and ERβ-immunopositive cells were present in SNR and SNC in both sexes and at all ages. ERα was not detected in male and female SNC at PN0-PN1. In both substantia nigra (SN) regions, there were developmentally regulated sex differences in AR, ERα and ERβ immunoreactivity. In the SN, each receptor showed specific intracellular localization: AR was present in the nucleus, ERα and ERβ were present both in nuclear and extranuclear compartments. ERα was detected also in processes. At PN0-PN1, quantitative analysis revealed sex and regional differences in the distribution of SN cells expressing AR and ERα, while ERβ were equally present in both sexes. The presence of gonadal steroid receptors in the SN suggests that the biological effects of gonadal hormones in the CNS extend beyond reproduction-related functions and may affect and modify motor behaviors (including seizures) in a sex-specific manner. Based on the ontogeny of SNR ERβ, we hypothesize that postnatal injections of testosterone may regulate the nigral GABA_A system through the aromatization pathway and activation of ERβ.

Original language	English (US)
Pages (from-to)	685-696
Number of pages	12
Journal	Neuroscience
Volume	115
Issue number	3
DOIs	https://doi.org/10.1016/S0306-4522(02)00491-8
State	Published - Dec 9 2002

Keywords

Gonadal steroid receptors
Midbrain
Ontogeny
Protein expression
Rodent
Sexual dimorphism

ASJC Scopus subject areas

Neuroscience(all)

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@article{dd1e6463a26e4b2f8aadbe0c673a2809,

title = "Sex differences in androgen and estrogen receptor expression in rat substantia nigra during development: An immunohistochemical study",

abstract = "Gonadal hormones are important regulators of sexual differentiation of the CNS. Exposure to testosterone and estrogen during development causes permanent organizational differences between males and females. We previously described functional sex-related differences of the GABAAergic circuits of the rat substantia nigra pars reticulata (SNR) involved in the control of flurothyl seizures. This sexual differentiation of the SNR is regulated by postnatal testosterone. To assess whether the organizing effects of testosterone in the SNR are mediated via the androgen receptor (AR) and/or estrogen receptors (ER), we used immunohistochemistry to study the ontogeny of AR, ERα and ERβ expression in SNR and substantia nigra pars compacta (SNC) of male and female rats. Rats on the day of birth [postnatal day (PN) 0] and at PN1, PN5, PN15 and PN30 were used. AR- and ERβ-immunopositive cells were present in SNR and SNC in both sexes and at all ages. ERα was not detected in male and female SNC at PN0-PN1. In both substantia nigra (SN) regions, there were developmentally regulated sex differences in AR, ERα and ERβ immunoreactivity. In the SN, each receptor showed specific intracellular localization: AR was present in the nucleus, ERα and ERβ were present both in nuclear and extranuclear compartments. ERα was detected also in processes. At PN0-PN1, quantitative analysis revealed sex and regional differences in the distribution of SN cells expressing AR and ERα, while ERβ were equally present in both sexes. The presence of gonadal steroid receptors in the SN suggests that the biological effects of gonadal hormones in the CNS extend beyond reproduction-related functions and may affect and modify motor behaviors (including seizures) in a sex-specific manner. Based on the ontogeny of SNR ERβ, we hypothesize that postnatal injections of testosterone may regulate the nigral GABAA system through the aromatization pathway and activation of ERβ.",

keywords = "Gonadal steroid receptors, Midbrain, Ontogeny, Protein expression, Rodent, Sexual dimorphism",

author = "T. Ravizza and Galanopoulou, {A. S.} and J. Vel{\'i}{\v s}kov{\'a} and Mosh{\'e}, {S. L.}",

note = "Funding Information: The two different ER showed distinct patterns of expression within the SN, suggestive of a different functional role. This hypothesis is supported by the available literature. The two ER differ in their distribution within the brain ( Shughrue et al., 1997 ), transactivation properties ( Paech et al., 1997 ) and affinity for various compounds ( Pettersson and Gustafsson, 2001 ). In SK-N-BE neuroblastoma cells transfected with either ERα or ERβ, estradiol induces different neuronal phenotypes. Morphological analysis revealed that activation of ERα causes an increase of neuronal arborization, suggesting a role in synaptic plasticity, while ERβ activation modulates neurite elongation, suggesting a role in neuronal differentiation ( Patrone et al., 2000 ). Our data showing that only ERα is present in neuronal processes may support this hypothesis. ",

year = "2002",

month = dec,

day = "9",

doi = "10.1016/S0306-4522(02)00491-8",

language = "English (US)",

volume = "115",

pages = "685--696",

journal = "Neuroscience",

issn = "0306-4522",

publisher = "Elsevier Limited",

number = "3",

}

TY - JOUR

T1 - Sex differences in androgen and estrogen receptor expression in rat substantia nigra during development

T2 - An immunohistochemical study

AU - Ravizza, T.

AU - Galanopoulou, A. S.

AU - Velíšková, J.

AU - Moshé, S. L.

N1 - Funding Information: The two different ER showed distinct patterns of expression within the SN, suggestive of a different functional role. This hypothesis is supported by the available literature. The two ER differ in their distribution within the brain ( Shughrue et al., 1997 ), transactivation properties ( Paech et al., 1997 ) and affinity for various compounds ( Pettersson and Gustafsson, 2001 ). In SK-N-BE neuroblastoma cells transfected with either ERα or ERβ, estradiol induces different neuronal phenotypes. Morphological analysis revealed that activation of ERα causes an increase of neuronal arborization, suggesting a role in synaptic plasticity, while ERβ activation modulates neurite elongation, suggesting a role in neuronal differentiation ( Patrone et al., 2000 ). Our data showing that only ERα is present in neuronal processes may support this hypothesis.

PY - 2002/12/9

Y1 - 2002/12/9

N2 - Gonadal hormones are important regulators of sexual differentiation of the CNS. Exposure to testosterone and estrogen during development causes permanent organizational differences between males and females. We previously described functional sex-related differences of the GABAAergic circuits of the rat substantia nigra pars reticulata (SNR) involved in the control of flurothyl seizures. This sexual differentiation of the SNR is regulated by postnatal testosterone. To assess whether the organizing effects of testosterone in the SNR are mediated via the androgen receptor (AR) and/or estrogen receptors (ER), we used immunohistochemistry to study the ontogeny of AR, ERα and ERβ expression in SNR and substantia nigra pars compacta (SNC) of male and female rats. Rats on the day of birth [postnatal day (PN) 0] and at PN1, PN5, PN15 and PN30 were used. AR- and ERβ-immunopositive cells were present in SNR and SNC in both sexes and at all ages. ERα was not detected in male and female SNC at PN0-PN1. In both substantia nigra (SN) regions, there were developmentally regulated sex differences in AR, ERα and ERβ immunoreactivity. In the SN, each receptor showed specific intracellular localization: AR was present in the nucleus, ERα and ERβ were present both in nuclear and extranuclear compartments. ERα was detected also in processes. At PN0-PN1, quantitative analysis revealed sex and regional differences in the distribution of SN cells expressing AR and ERα, while ERβ were equally present in both sexes. The presence of gonadal steroid receptors in the SN suggests that the biological effects of gonadal hormones in the CNS extend beyond reproduction-related functions and may affect and modify motor behaviors (including seizures) in a sex-specific manner. Based on the ontogeny of SNR ERβ, we hypothesize that postnatal injections of testosterone may regulate the nigral GABAA system through the aromatization pathway and activation of ERβ.

AB - Gonadal hormones are important regulators of sexual differentiation of the CNS. Exposure to testosterone and estrogen during development causes permanent organizational differences between males and females. We previously described functional sex-related differences of the GABAAergic circuits of the rat substantia nigra pars reticulata (SNR) involved in the control of flurothyl seizures. This sexual differentiation of the SNR is regulated by postnatal testosterone. To assess whether the organizing effects of testosterone in the SNR are mediated via the androgen receptor (AR) and/or estrogen receptors (ER), we used immunohistochemistry to study the ontogeny of AR, ERα and ERβ expression in SNR and substantia nigra pars compacta (SNC) of male and female rats. Rats on the day of birth [postnatal day (PN) 0] and at PN1, PN5, PN15 and PN30 were used. AR- and ERβ-immunopositive cells were present in SNR and SNC in both sexes and at all ages. ERα was not detected in male and female SNC at PN0-PN1. In both substantia nigra (SN) regions, there were developmentally regulated sex differences in AR, ERα and ERβ immunoreactivity. In the SN, each receptor showed specific intracellular localization: AR was present in the nucleus, ERα and ERβ were present both in nuclear and extranuclear compartments. ERα was detected also in processes. At PN0-PN1, quantitative analysis revealed sex and regional differences in the distribution of SN cells expressing AR and ERα, while ERβ were equally present in both sexes. The presence of gonadal steroid receptors in the SN suggests that the biological effects of gonadal hormones in the CNS extend beyond reproduction-related functions and may affect and modify motor behaviors (including seizures) in a sex-specific manner. Based on the ontogeny of SNR ERβ, we hypothesize that postnatal injections of testosterone may regulate the nigral GABAA system through the aromatization pathway and activation of ERβ.

KW - Gonadal steroid receptors

KW - Midbrain

KW - Ontogeny

KW - Protein expression

KW - Rodent

KW - Sexual dimorphism

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U2 - 10.1016/S0306-4522(02)00491-8

DO - 10.1016/S0306-4522(02)00491-8

M3 - Article

C2 - 12435407

AN - SCOPUS:0037049245

VL - 115

SP - 685

EP - 696

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 3

ER -