Molecular basis of mineralocorticoid receptor action in the nervous system

Autores
Molinari, Alejandro Martín; Machado Rada, Mayra Y.; Mazaira, Gisela Ileana; Erlejman, Alejandra Giselle; Galigniana, Mario Daniel
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The most relevant biological action of aldosterone in epithelial tissues is the regulation of sodium reabsorption through binding to the mineralocorticoid receptor (MR). Glucocorticoids also bind with high affinity to MR, which is usually protected by the enzyme 11β-hydroxysteroid dehydrogenase. This activity prevents MR activation by cortisol despite the large prevalence of this steroid in plasma. Nonetheless, there are some aspects of the mechanism of action of MR that are not entirely explained by this competitive metabolic mechanism of protection. The picture is even more complicated in those tissues such as the nervous system where the enzyme is expressed at very low levels or is directly absent in various areas of the brain. Therefore, other cellular and molecular mechanisms must also intervene to allow specific aldosterone biological effects in the presence of overwhelming concentrations of glucocorticoids. In this article, we discuss some possible mechanisms that permit the specificity of action for each type of steroid, including those related to the recently discovered novel molecular mechanism of activation of corticosteroid receptors and the structural requirements of a given ligand to favor the mineralocorticoid action via MR. The relative contribution of these mechanisms may vary in different target cells allowing the fine tuning of cellular functions depending on the degree of cooperation between steroids, receptors, chaperones associated to receptors, and other factors. All these regulatory interactions can be altered in some pathophysiological situations, most of them related to stressing situations.
Fil: Molinari, Alejandro Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Machado Rada, Mayra Y.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Mazaira, Gisela Ileana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Erlejman, Alejandra Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
Esteroides
Hipocampo
Receptor de Mineralocorticoides
Receptor de Glucocorticoides
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/7356
Acceder
id CONICETDig_d489a4d2ce414e642ac9d707c8d1b95f
oai_identifier_str oai:ri.conicet.gov.ar:11336/7356
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular basis of mineralocorticoid receptor action in the nervous systemMolinari, Alejandro MartínMachado Rada, Mayra Y.Mazaira, Gisela IleanaErlejman, Alejandra GiselleGaligniana, Mario DanielEsteroidesHipocampoReceptor de MineralocorticoidesReceptor de Glucocorticoideshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The most relevant biological action of aldosterone in epithelial tissues is the regulation of sodium reabsorption through binding to the mineralocorticoid receptor (MR). Glucocorticoids also bind with high affinity to MR, which is usually protected by the enzyme 11β-hydroxysteroid dehydrogenase. This activity prevents MR activation by cortisol despite the large prevalence of this steroid in plasma. Nonetheless, there are some aspects of the mechanism of action of MR that are not entirely explained by this competitive metabolic mechanism of protection. The picture is even more complicated in those tissues such as the nervous system where the enzyme is expressed at very low levels or is directly absent in various areas of the brain. Therefore, other cellular and molecular mechanisms must also intervene to allow specific aldosterone biological effects in the presence of overwhelming concentrations of glucocorticoids. In this article, we discuss some possible mechanisms that permit the specificity of action for each type of steroid, including those related to the recently discovered novel molecular mechanism of activation of corticosteroid receptors and the structural requirements of a given ligand to favor the mineralocorticoid action via MR. The relative contribution of these mechanisms may vary in different target cells allowing the fine tuning of cellular functions depending on the degree of cooperation between steroids, receptors, chaperones associated to receptors, and other factors. All these regulatory interactions can be altered in some pathophysiological situations, most of them related to stressing situations.Fil: Molinari, Alejandro Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Machado Rada, Mayra Y.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Mazaira, Gisela Ileana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Erlejman, Alejandra Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaBentham Science Publishers2013-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7356Molinari, Alejandro Martín; Machado Rada, Mayra Y.; Mazaira, Gisela Ileana; Erlejman, Alejandra Giselle; Galigniana, Mario Daniel; Molecular basis of mineralocorticoid receptor action in the nervous system; Bentham Science Publishers; Cns & Neurological Disorders-drug Targets; 12; 8; 12-2013; 1163-11741871-5273enginfo:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/115012/articleinfo:eu-repo/semantics/altIdentifier/doi/10.2174/187152731131200122info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:44Zoai:ri.conicet.gov.ar:11336/7356instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:47:44.62CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular basis of mineralocorticoid receptor action in the nervous system
title Molecular basis of mineralocorticoid receptor action in the nervous system
spellingShingle Molecular basis of mineralocorticoid receptor action in the nervous system
Molinari, Alejandro Martín
Esteroides
Hipocampo
Receptor de Mineralocorticoides
Receptor de Glucocorticoides
title_short Molecular basis of mineralocorticoid receptor action in the nervous system
title_full Molecular basis of mineralocorticoid receptor action in the nervous system
title_fullStr Molecular basis of mineralocorticoid receptor action in the nervous system
title_full_unstemmed Molecular basis of mineralocorticoid receptor action in the nervous system
title_sort Molecular basis of mineralocorticoid receptor action in the nervous system
dc.creator.none.fl_str_mv Molinari, Alejandro Martín
Machado Rada, Mayra Y.
Mazaira, Gisela Ileana
Erlejman, Alejandra Giselle
Galigniana, Mario Daniel
author Molinari, Alejandro Martín
author_facet Molinari, Alejandro Martín
Machado Rada, Mayra Y.
Mazaira, Gisela Ileana
Erlejman, Alejandra Giselle
Galigniana, Mario Daniel
author_role author
author2 Machado Rada, Mayra Y.
Mazaira, Gisela Ileana
Erlejman, Alejandra Giselle
Galigniana, Mario Daniel
author2_role author
author
author
author
dc.subject.none.fl_str_mv Esteroides
Hipocampo
Receptor de Mineralocorticoides
Receptor de Glucocorticoides
topic Esteroides
Hipocampo
Receptor de Mineralocorticoides
Receptor de Glucocorticoides
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The most relevant biological action of aldosterone in epithelial tissues is the regulation of sodium reabsorption through binding to the mineralocorticoid receptor (MR). Glucocorticoids also bind with high affinity to MR, which is usually protected by the enzyme 11β-hydroxysteroid dehydrogenase. This activity prevents MR activation by cortisol despite the large prevalence of this steroid in plasma. Nonetheless, there are some aspects of the mechanism of action of MR that are not entirely explained by this competitive metabolic mechanism of protection. The picture is even more complicated in those tissues such as the nervous system where the enzyme is expressed at very low levels or is directly absent in various areas of the brain. Therefore, other cellular and molecular mechanisms must also intervene to allow specific aldosterone biological effects in the presence of overwhelming concentrations of glucocorticoids. In this article, we discuss some possible mechanisms that permit the specificity of action for each type of steroid, including those related to the recently discovered novel molecular mechanism of activation of corticosteroid receptors and the structural requirements of a given ligand to favor the mineralocorticoid action via MR. The relative contribution of these mechanisms may vary in different target cells allowing the fine tuning of cellular functions depending on the degree of cooperation between steroids, receptors, chaperones associated to receptors, and other factors. All these regulatory interactions can be altered in some pathophysiological situations, most of them related to stressing situations.
Fil: Molinari, Alejandro Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Machado Rada, Mayra Y.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Mazaira, Gisela Ileana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Erlejman, Alejandra Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description The most relevant biological action of aldosterone in epithelial tissues is the regulation of sodium reabsorption through binding to the mineralocorticoid receptor (MR). Glucocorticoids also bind with high affinity to MR, which is usually protected by the enzyme 11β-hydroxysteroid dehydrogenase. This activity prevents MR activation by cortisol despite the large prevalence of this steroid in plasma. Nonetheless, there are some aspects of the mechanism of action of MR that are not entirely explained by this competitive metabolic mechanism of protection. The picture is even more complicated in those tissues such as the nervous system where the enzyme is expressed at very low levels or is directly absent in various areas of the brain. Therefore, other cellular and molecular mechanisms must also intervene to allow specific aldosterone biological effects in the presence of overwhelming concentrations of glucocorticoids. In this article, we discuss some possible mechanisms that permit the specificity of action for each type of steroid, including those related to the recently discovered novel molecular mechanism of activation of corticosteroid receptors and the structural requirements of a given ligand to favor the mineralocorticoid action via MR. The relative contribution of these mechanisms may vary in different target cells allowing the fine tuning of cellular functions depending on the degree of cooperation between steroids, receptors, chaperones associated to receptors, and other factors. All these regulatory interactions can be altered in some pathophysiological situations, most of them related to stressing situations.
publishDate 2013
dc.date.none.fl_str_mv 2013-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/7356
Molinari, Alejandro Martín; Machado Rada, Mayra Y.; Mazaira, Gisela Ileana; Erlejman, Alejandra Giselle; Galigniana, Mario Daniel; Molecular basis of mineralocorticoid receptor action in the nervous system; Bentham Science Publishers; Cns & Neurological Disorders-drug Targets; 12; 8; 12-2013; 1163-1174
1871-5273
url http://hdl.handle.net/11336/7356
identifier_str_mv Molinari, Alejandro Martín; Machado Rada, Mayra Y.; Mazaira, Gisela Ileana; Erlejman, Alejandra Giselle; Galigniana, Mario Daniel; Molecular basis of mineralocorticoid receptor action in the nervous system; Bentham Science Publishers; Cns & Neurological Disorders-drug Targets; 12; 8; 12-2013; 1163-1174
1871-5273
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/115012/article
info:eu-repo/semantics/altIdentifier/doi/10.2174/187152731131200122
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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