Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment

Autores
Calfa, Gaston Diego; Kademian, S.; Ceschin, Danilo Guillermo; Vega, G.; Rabinovich, Gabriel Adrián; Volosin, M.
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hyperactivity of the hypothalamic pituitary adrenal (HPA) axis in patients with major depression is one of the most consistent findings in biological psychiatry. Experimental data support the idea that glucocorticoid-mediated feedback via glucocorticoid receptors (GR) is impaired in major depression. The aim of the present work was to assess the putative changes in GR density of peripheral blood mononuclear cells (PBMCs) in a group of patients with major depression and to determine modulation of these GR sites by antidepressant treatment. In addition, susceptibility of PBMCs to glucocorticoid effects was also studied using a functional end-point analysis in vitro, such as cortisol inhibition of mitogen-induced lymphocyte proliferation. Cortisol levels were also measured before and after dexamethasone suppression test (DST). The results showed a decrease in GR density in depressed patients compared with healthy subjects, mainly in those patients that showed basal cortisol levels in the upper normal range and were refractory to DST. Regarding the functional significance of this variation, two representative groups emerged from our study: a) free-medication patients with GR function comparable to healthy controls, and b) patients showing diminished GR activity. These results suggest a lack of relationship between GR density and cortisol-induced inhibition of lymphocyte proliferation. Patients treated with different antidepressant drugs showed a marked increase in the number of GR sites per cell compared to non-treated. Interestingly, this increase was even higher than in normal subjects. Hence, restoration of GR density after an efficient antidepressant treatment could be an index of an effective modulatory action of drugs on GR expression and highlights the possibility that GR levels might be used as markers of a successful treatment. © 2003 Elsevier Science Ltd. All rights reserved.
Fil: Calfa, Gaston Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
Fil: Kademian, S.. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
Fil: Ceschin, Danilo Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
Fil: Vega, G.. PSIQUE; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Volosin, M.. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
Materia
Antidepressant Treatment
Cortisol
Gucocorticoid Receptors
Hypothalamus-Pituitary-Adrenal Axis
Lymphocyte Stimulation
Major Depression
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:11336/52030
Acceder
id CONICETDig_5e82fcf4192c5d0247d9e3f99aad3eac
oai_identifier_str oai:ri.conicet.gov.ar:11336/52030
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatmentCalfa, Gaston DiegoKademian, S.Ceschin, Danilo GuillermoVega, G.Rabinovich, Gabriel AdriánVolosin, M.Antidepressant TreatmentCortisolGucocorticoid ReceptorsHypothalamus-Pituitary-Adrenal AxisLymphocyte StimulationMajor Depressionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Hyperactivity of the hypothalamic pituitary adrenal (HPA) axis in patients with major depression is one of the most consistent findings in biological psychiatry. Experimental data support the idea that glucocorticoid-mediated feedback via glucocorticoid receptors (GR) is impaired in major depression. The aim of the present work was to assess the putative changes in GR density of peripheral blood mononuclear cells (PBMCs) in a group of patients with major depression and to determine modulation of these GR sites by antidepressant treatment. In addition, susceptibility of PBMCs to glucocorticoid effects was also studied using a functional end-point analysis in vitro, such as cortisol inhibition of mitogen-induced lymphocyte proliferation. Cortisol levels were also measured before and after dexamethasone suppression test (DST). The results showed a decrease in GR density in depressed patients compared with healthy subjects, mainly in those patients that showed basal cortisol levels in the upper normal range and were refractory to DST. Regarding the functional significance of this variation, two representative groups emerged from our study: a) free-medication patients with GR function comparable to healthy controls, and b) patients showing diminished GR activity. These results suggest a lack of relationship between GR density and cortisol-induced inhibition of lymphocyte proliferation. Patients treated with different antidepressant drugs showed a marked increase in the number of GR sites per cell compared to non-treated. Interestingly, this increase was even higher than in normal subjects. Hence, restoration of GR density after an efficient antidepressant treatment could be an index of an effective modulatory action of drugs on GR expression and highlights the possibility that GR levels might be used as markers of a successful treatment. © 2003 Elsevier Science Ltd. All rights reserved.Fil: Calfa, Gaston Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; ArgentinaFil: Kademian, S.. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; ArgentinaFil: Ceschin, Danilo Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; ArgentinaFil: Vega, G.. PSIQUE; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Volosin, M.. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; ArgentinaPergamon-Elsevier Science Ltd2003-06info: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/11336/52030Calfa, Gaston Diego; Kademian, S.; Ceschin, Danilo Guillermo; Vega, G.; Rabinovich, Gabriel Adrián; et al.; Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment; Pergamon-Elsevier Science Ltd; Psychoneuroendocrinology; 28; 5; 6-2003; 687-7010306-4530CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/S0306-4530(02)00051-3info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0306453002000513info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:00Zoai:ri.conicet.gov.ar:11336/52030instacron: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 09:33:00.955CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment
title Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment
spellingShingle Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment
Calfa, Gaston Diego
Antidepressant Treatment
Cortisol
Gucocorticoid Receptors
Hypothalamus-Pituitary-Adrenal Axis
Lymphocyte Stimulation
Major Depression
title_short Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment
title_full Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment
title_fullStr Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment
title_full_unstemmed Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment
title_sort Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment
dc.creator.none.fl_str_mv Calfa, Gaston Diego
Kademian, S.
Ceschin, Danilo Guillermo
Vega, G.
Rabinovich, Gabriel Adrián
Volosin, M.
author Calfa, Gaston Diego
author_facet Calfa, Gaston Diego
Kademian, S.
Ceschin, Danilo Guillermo
Vega, G.
Rabinovich, Gabriel Adrián
Volosin, M.
author_role author
author2 Kademian, S.
Ceschin, Danilo Guillermo
Vega, G.
Rabinovich, Gabriel Adrián
Volosin, M.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Antidepressant Treatment
Cortisol
Gucocorticoid Receptors
Hypothalamus-Pituitary-Adrenal Axis
Lymphocyte Stimulation
Major Depression
topic Antidepressant Treatment
Cortisol
Gucocorticoid Receptors
Hypothalamus-Pituitary-Adrenal Axis
Lymphocyte Stimulation
Major Depression
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hyperactivity of the hypothalamic pituitary adrenal (HPA) axis in patients with major depression is one of the most consistent findings in biological psychiatry. Experimental data support the idea that glucocorticoid-mediated feedback via glucocorticoid receptors (GR) is impaired in major depression. The aim of the present work was to assess the putative changes in GR density of peripheral blood mononuclear cells (PBMCs) in a group of patients with major depression and to determine modulation of these GR sites by antidepressant treatment. In addition, susceptibility of PBMCs to glucocorticoid effects was also studied using a functional end-point analysis in vitro, such as cortisol inhibition of mitogen-induced lymphocyte proliferation. Cortisol levels were also measured before and after dexamethasone suppression test (DST). The results showed a decrease in GR density in depressed patients compared with healthy subjects, mainly in those patients that showed basal cortisol levels in the upper normal range and were refractory to DST. Regarding the functional significance of this variation, two representative groups emerged from our study: a) free-medication patients with GR function comparable to healthy controls, and b) patients showing diminished GR activity. These results suggest a lack of relationship between GR density and cortisol-induced inhibition of lymphocyte proliferation. Patients treated with different antidepressant drugs showed a marked increase in the number of GR sites per cell compared to non-treated. Interestingly, this increase was even higher than in normal subjects. Hence, restoration of GR density after an efficient antidepressant treatment could be an index of an effective modulatory action of drugs on GR expression and highlights the possibility that GR levels might be used as markers of a successful treatment. © 2003 Elsevier Science Ltd. All rights reserved.
Fil: Calfa, Gaston Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
Fil: Kademian, S.. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
Fil: Ceschin, Danilo Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
Fil: Vega, G.. PSIQUE; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Volosin, M.. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
description Hyperactivity of the hypothalamic pituitary adrenal (HPA) axis in patients with major depression is one of the most consistent findings in biological psychiatry. Experimental data support the idea that glucocorticoid-mediated feedback via glucocorticoid receptors (GR) is impaired in major depression. The aim of the present work was to assess the putative changes in GR density of peripheral blood mononuclear cells (PBMCs) in a group of patients with major depression and to determine modulation of these GR sites by antidepressant treatment. In addition, susceptibility of PBMCs to glucocorticoid effects was also studied using a functional end-point analysis in vitro, such as cortisol inhibition of mitogen-induced lymphocyte proliferation. Cortisol levels were also measured before and after dexamethasone suppression test (DST). The results showed a decrease in GR density in depressed patients compared with healthy subjects, mainly in those patients that showed basal cortisol levels in the upper normal range and were refractory to DST. Regarding the functional significance of this variation, two representative groups emerged from our study: a) free-medication patients with GR function comparable to healthy controls, and b) patients showing diminished GR activity. These results suggest a lack of relationship between GR density and cortisol-induced inhibition of lymphocyte proliferation. Patients treated with different antidepressant drugs showed a marked increase in the number of GR sites per cell compared to non-treated. Interestingly, this increase was even higher than in normal subjects. Hence, restoration of GR density after an efficient antidepressant treatment could be an index of an effective modulatory action of drugs on GR expression and highlights the possibility that GR levels might be used as markers of a successful treatment. © 2003 Elsevier Science Ltd. All rights reserved.
publishDate 2003
dc.date.none.fl_str_mv 2003-06
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/11336/52030
Calfa, Gaston Diego; Kademian, S.; Ceschin, Danilo Guillermo; Vega, G.; Rabinovich, Gabriel Adrián; et al.; Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment; Pergamon-Elsevier Science Ltd; Psychoneuroendocrinology; 28; 5; 6-2003; 687-701
0306-4530
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52030
identifier_str_mv Calfa, Gaston Diego; Kademian, S.; Ceschin, Danilo Guillermo; Vega, G.; Rabinovich, Gabriel Adrián; et al.; Characterization and functional significance of glucocorticoid receptors in patients with major depression: Modulation by antidepressant treatment; Pergamon-Elsevier Science Ltd; Psychoneuroendocrinology; 28; 5; 6-2003; 687-701
0306-4530
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/S0306-4530(02)00051-3
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0306453002000513
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 Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
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
_version_ 1844613011206045696
score 13.070432

Publicaciones similares