Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship

Autores
Galigniana, Mario Daniel; Piwien Pilipuk, Graciela
Año de publicación
2004
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The mineralocorticoid effect on epithelial cells is the resultant of an intricate net of biochemical regulations that ultimately leads to the maintenance of electrolyte homeostasis. Two key protagonists in this plot are the ligand, which broadcasts the information, and the receptor, which functions as a receiver and transducer. Therefore, the responsibility for the final biological effect is not limited to each individual component but to both of them, so they constitute a functional unit. In addition, several prereceptor regulatory mechanisms are also determinant factors for the final biological response. Because steroids are present in both animals and plants and are derived from common precursors, it is intriguing how these simple molecules have acquired specialization to shape biological development and differentiation. This is particularly true for the function of aldosterone in mammals, which is mimicked by glucocorticoids or progesterone in some particular cases. Inasmuch as the most potent mineralocorticoid in nature, aldosterone, shows a poorly angled steroid nucleus at the A?B-ring junction, and because steroids that possess identical functional groups and different steroidal frames elicit different mineralocorticoid effects, we postulate that a planar conformation of the ligand is a key requirement to acquire potent sodium retention properties. The model takes into consideration all the mechanisms involved in the regulation of the final biological effect, although it does not provide a definitive answer to the original question. It is also discussed how the use of novel mineralocorticoid ligands may shed light on the still obscure mechanism of action of the mineralocorticoid receptor.
Fil: Galigniana, Mario Daniel. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Piwien Pilipuk, Graciela. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Aldosterone
Natriuresis
Mineralcorticoids
Molecular Conformation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/29122

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network_name_str CONICET Digital (CONICET)
spelling Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationshipGaligniana, Mario DanielPiwien Pilipuk, GracielaAldosteroneNatriuresisMineralcorticoidsMolecular Conformationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The mineralocorticoid effect on epithelial cells is the resultant of an intricate net of biochemical regulations that ultimately leads to the maintenance of electrolyte homeostasis. Two key protagonists in this plot are the ligand, which broadcasts the information, and the receptor, which functions as a receiver and transducer. Therefore, the responsibility for the final biological effect is not limited to each individual component but to both of them, so they constitute a functional unit. In addition, several prereceptor regulatory mechanisms are also determinant factors for the final biological response. Because steroids are present in both animals and plants and are derived from common precursors, it is intriguing how these simple molecules have acquired specialization to shape biological development and differentiation. This is particularly true for the function of aldosterone in mammals, which is mimicked by glucocorticoids or progesterone in some particular cases. Inasmuch as the most potent mineralocorticoid in nature, aldosterone, shows a poorly angled steroid nucleus at the A?B-ring junction, and because steroids that possess identical functional groups and different steroidal frames elicit different mineralocorticoid effects, we postulate that a planar conformation of the ligand is a key requirement to acquire potent sodium retention properties. The model takes into consideration all the mechanisms involved in the regulation of the final biological effect, although it does not provide a definitive answer to the original question. It is also discussed how the use of novel mineralocorticoid ligands may shed light on the still obscure mechanism of action of the mineralocorticoid receptor.Fil: Galigniana, Mario Daniel. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piwien Pilipuk, Graciela. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Inc2004info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/29122Galigniana, Mario Daniel; Piwien Pilipuk, Graciela; Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship; Elsevier Inc; Vitamins And Hormones Series; 69; -1-2004; 31-680083-67290083-6729CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0083672904690029?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/S0083-6729(04)69002-9info:eu-repo/semantics/altIdentifier/pmid/15196878info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:33:01Zoai:ri.conicet.gov.ar:11336/29122instacron: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 10:33:01.333CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship
title Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship
spellingShingle Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship
Galigniana, Mario Daniel
Aldosterone
Natriuresis
Mineralcorticoids
Molecular Conformation
title_short Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship
title_full Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship
title_fullStr Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship
title_full_unstemmed Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship
title_sort Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship
dc.creator.none.fl_str_mv Galigniana, Mario Daniel
Piwien Pilipuk, Graciela
author Galigniana, Mario Daniel
author_facet Galigniana, Mario Daniel
Piwien Pilipuk, Graciela
author_role author
author2 Piwien Pilipuk, Graciela
author2_role author
dc.subject.none.fl_str_mv Aldosterone
Natriuresis
Mineralcorticoids
Molecular Conformation
topic Aldosterone
Natriuresis
Mineralcorticoids
Molecular Conformation
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 mineralocorticoid effect on epithelial cells is the resultant of an intricate net of biochemical regulations that ultimately leads to the maintenance of electrolyte homeostasis. Two key protagonists in this plot are the ligand, which broadcasts the information, and the receptor, which functions as a receiver and transducer. Therefore, the responsibility for the final biological effect is not limited to each individual component but to both of them, so they constitute a functional unit. In addition, several prereceptor regulatory mechanisms are also determinant factors for the final biological response. Because steroids are present in both animals and plants and are derived from common precursors, it is intriguing how these simple molecules have acquired specialization to shape biological development and differentiation. This is particularly true for the function of aldosterone in mammals, which is mimicked by glucocorticoids or progesterone in some particular cases. Inasmuch as the most potent mineralocorticoid in nature, aldosterone, shows a poorly angled steroid nucleus at the A?B-ring junction, and because steroids that possess identical functional groups and different steroidal frames elicit different mineralocorticoid effects, we postulate that a planar conformation of the ligand is a key requirement to acquire potent sodium retention properties. The model takes into consideration all the mechanisms involved in the regulation of the final biological effect, although it does not provide a definitive answer to the original question. It is also discussed how the use of novel mineralocorticoid ligands may shed light on the still obscure mechanism of action of the mineralocorticoid receptor.
Fil: Galigniana, Mario Daniel. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Piwien Pilipuk, Graciela. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The mineralocorticoid effect on epithelial cells is the resultant of an intricate net of biochemical regulations that ultimately leads to the maintenance of electrolyte homeostasis. Two key protagonists in this plot are the ligand, which broadcasts the information, and the receptor, which functions as a receiver and transducer. Therefore, the responsibility for the final biological effect is not limited to each individual component but to both of them, so they constitute a functional unit. In addition, several prereceptor regulatory mechanisms are also determinant factors for the final biological response. Because steroids are present in both animals and plants and are derived from common precursors, it is intriguing how these simple molecules have acquired specialization to shape biological development and differentiation. This is particularly true for the function of aldosterone in mammals, which is mimicked by glucocorticoids or progesterone in some particular cases. Inasmuch as the most potent mineralocorticoid in nature, aldosterone, shows a poorly angled steroid nucleus at the A?B-ring junction, and because steroids that possess identical functional groups and different steroidal frames elicit different mineralocorticoid effects, we postulate that a planar conformation of the ligand is a key requirement to acquire potent sodium retention properties. The model takes into consideration all the mechanisms involved in the regulation of the final biological effect, although it does not provide a definitive answer to the original question. It is also discussed how the use of novel mineralocorticoid ligands may shed light on the still obscure mechanism of action of the mineralocorticoid receptor.
publishDate 2004
dc.date.none.fl_str_mv 2004
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/11336/29122
Galigniana, Mario Daniel; Piwien Pilipuk, Graciela; Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship; Elsevier Inc; Vitamins And Hormones Series; 69; -1-2004; 31-68
0083-6729
0083-6729
CONICET Digital
CONICET
url http://hdl.handle.net/11336/29122
identifier_str_mv Galigniana, Mario Daniel; Piwien Pilipuk, Graciela; Activation of the ligand-mineralocorticoid receptor functional unit by ancient, classical, and novel ligands: structure-activity relationship; Elsevier Inc; Vitamins And Hormones Series; 69; -1-2004; 31-68
0083-6729
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0083672904690029?via%3Dihub
info:eu-repo/semantics/altIdentifier/doi/10.1016/S0083-6729(04)69002-9
info:eu-repo/semantics/altIdentifier/pmid/15196878
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Inc
publisher.none.fl_str_mv Elsevier Inc
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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