New insights into melatonin signaling in hamster Leydig cells

Autores
Rossi, Soledad Paola; Matzkin, Maria Eugenia; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; Levalle, Oscar; Calandra, Ricardo Saul; Frungieri, Monica Beatriz
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have previously described that melatonin inhibits androgen production in hamster testes via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. This study attempted to determine the initial events of the melatonin/CRH signaling pathway. In Leydig cells from reproductively active Syrian hamsters, Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and a colorimetric assay demonstrated that melatonin and CRH activate tyrosine phosphatases and subsequently reduce the phosphorylation levels of extracellular signal-regulated kinase (erk) and c-jun N-terminal kinase (jnk), down-regulate the expression of c-jun, c-fos and steroidogenic acute regulatory (StAR), and inhibit the production of testosterone. These effects were prevented by a highly selective CRH antagonist, thus indicating that melatonin does not exert a direct role. Specific mitogen-activated protein kinase kinase (MEK) and jnk blockers inhibited expression of c-jun, c-fos, StAR and the production of testosterone, confirming that these are events triggered downstream of erk and jnk. In Leydig cells from photoperiodically regressed adult hamsters, CRH inhibited the production of androstane-3α,17β-diol (3α-diol), the main androgen produced, through the same signaling pathway. Testicular melatonin concentration was 3-4-fold higher in reproductively inactive hamsters than that detected in active animals. Since melatonin, CRH, and their receptors are present not only in hamster testes but also in testicular biopsies of infertile men, we can conjecture about the relevance of this previously uncharacterized pathway in human fertility disorders. In summary, our study identifies crucial intracellular events triggered by melatonin/CRH in the testis that lead to a down-regulation of the steroidogenic process.
Fil: Rossi, Soledad Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Matzkin, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Terradas, Claudio. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Ponzio, Roberto. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Puigdomenech, Elisa. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Levalle, Oscar. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Calandra, Ricardo Saul. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Materia
Melatonin
Leydig Cells
Intracellular Signalingi
Tyrosine Phosphatases
Testosterone
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:11336/9852
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/9852
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling New insights into melatonin signaling in hamster Leydig cellsRossi, Soledad PaolaMatzkin, Maria EugeniaTerradas, ClaudioPonzio, RobertoPuigdomenech, ElisaLevalle, OscarCalandra, Ricardo SaulFrungieri, Monica BeatrizMelatoninLeydig CellsIntracellular SignalingiTyrosine PhosphatasesTestosteronehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have previously described that melatonin inhibits androgen production in hamster testes via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. This study attempted to determine the initial events of the melatonin/CRH signaling pathway. In Leydig cells from reproductively active Syrian hamsters, Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and a colorimetric assay demonstrated that melatonin and CRH activate tyrosine phosphatases and subsequently reduce the phosphorylation levels of extracellular signal-regulated kinase (erk) and c-jun N-terminal kinase (jnk), down-regulate the expression of c-jun, c-fos and steroidogenic acute regulatory (StAR), and inhibit the production of testosterone. These effects were prevented by a highly selective CRH antagonist, thus indicating that melatonin does not exert a direct role. Specific mitogen-activated protein kinase kinase (MEK) and jnk blockers inhibited expression of c-jun, c-fos, StAR and the production of testosterone, confirming that these are events triggered downstream of erk and jnk. In Leydig cells from photoperiodically regressed adult hamsters, CRH inhibited the production of androstane-3α,17β-diol (3α-diol), the main androgen produced, through the same signaling pathway. Testicular melatonin concentration was 3-4-fold higher in reproductively inactive hamsters than that detected in active animals. Since melatonin, CRH, and their receptors are present not only in hamster testes but also in testicular biopsies of infertile men, we can conjecture about the relevance of this previously uncharacterized pathway in human fertility disorders. In summary, our study identifies crucial intracellular events triggered by melatonin/CRH in the testis that lead to a down-regulation of the steroidogenic process.Fil: Rossi, Soledad Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Matzkin, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Terradas, Claudio. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Ponzio, Roberto. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Puigdomenech, Elisa. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Levalle, Oscar. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Calandra, Ricardo Saul. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaAcademic Press Inc Elsevier Science2012-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/9852Rossi, Soledad Paola; Matzkin, Maria Eugenia; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; et al.; New insights into melatonin signaling in hamster Leydig cells; Academic Press Inc Elsevier Science; General And Comparative Endocrinology; 178; 1; 8-2012; 153-1630016-64801095-6840enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ygcen.2012.04.031info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0016648012001955info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:27Zoai:ri.conicet.gov.ar:11336/9852instacron: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 09:40:27.68CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv New insights into melatonin signaling in hamster Leydig cells
title New insights into melatonin signaling in hamster Leydig cells
spellingShingle New insights into melatonin signaling in hamster Leydig cells
Rossi, Soledad Paola
Melatonin
Leydig Cells
Intracellular Signalingi
Tyrosine Phosphatases
Testosterone
title_short New insights into melatonin signaling in hamster Leydig cells
title_full New insights into melatonin signaling in hamster Leydig cells
title_fullStr New insights into melatonin signaling in hamster Leydig cells
title_full_unstemmed New insights into melatonin signaling in hamster Leydig cells
title_sort New insights into melatonin signaling in hamster Leydig cells
dc.creator.none.fl_str_mv Rossi, Soledad Paola
Matzkin, Maria Eugenia
Terradas, Claudio
Ponzio, Roberto
Puigdomenech, Elisa
Levalle, Oscar
Calandra, Ricardo Saul
Frungieri, Monica Beatriz
author Rossi, Soledad Paola
author_facet Rossi, Soledad Paola
Matzkin, Maria Eugenia
Terradas, Claudio
Ponzio, Roberto
Puigdomenech, Elisa
Levalle, Oscar
Calandra, Ricardo Saul
Frungieri, Monica Beatriz
author_role author
author2 Matzkin, Maria Eugenia
Terradas, Claudio
Ponzio, Roberto
Puigdomenech, Elisa
Levalle, Oscar
Calandra, Ricardo Saul
Frungieri, Monica Beatriz
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Melatonin
Leydig Cells
Intracellular Signalingi
Tyrosine Phosphatases
Testosterone
topic Melatonin
Leydig Cells
Intracellular Signalingi
Tyrosine Phosphatases
Testosterone
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We have previously described that melatonin inhibits androgen production in hamster testes via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. This study attempted to determine the initial events of the melatonin/CRH signaling pathway. In Leydig cells from reproductively active Syrian hamsters, Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and a colorimetric assay demonstrated that melatonin and CRH activate tyrosine phosphatases and subsequently reduce the phosphorylation levels of extracellular signal-regulated kinase (erk) and c-jun N-terminal kinase (jnk), down-regulate the expression of c-jun, c-fos and steroidogenic acute regulatory (StAR), and inhibit the production of testosterone. These effects were prevented by a highly selective CRH antagonist, thus indicating that melatonin does not exert a direct role. Specific mitogen-activated protein kinase kinase (MEK) and jnk blockers inhibited expression of c-jun, c-fos, StAR and the production of testosterone, confirming that these are events triggered downstream of erk and jnk. In Leydig cells from photoperiodically regressed adult hamsters, CRH inhibited the production of androstane-3α,17β-diol (3α-diol), the main androgen produced, through the same signaling pathway. Testicular melatonin concentration was 3-4-fold higher in reproductively inactive hamsters than that detected in active animals. Since melatonin, CRH, and their receptors are present not only in hamster testes but also in testicular biopsies of infertile men, we can conjecture about the relevance of this previously uncharacterized pathway in human fertility disorders. In summary, our study identifies crucial intracellular events triggered by melatonin/CRH in the testis that lead to a down-regulation of the steroidogenic process.
Fil: Rossi, Soledad Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Matzkin, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Terradas, Claudio. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Ponzio, Roberto. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Puigdomenech, Elisa. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Levalle, Oscar. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Calandra, Ricardo Saul. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
description We have previously described that melatonin inhibits androgen production in hamster testes via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. This study attempted to determine the initial events of the melatonin/CRH signaling pathway. In Leydig cells from reproductively active Syrian hamsters, Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and a colorimetric assay demonstrated that melatonin and CRH activate tyrosine phosphatases and subsequently reduce the phosphorylation levels of extracellular signal-regulated kinase (erk) and c-jun N-terminal kinase (jnk), down-regulate the expression of c-jun, c-fos and steroidogenic acute regulatory (StAR), and inhibit the production of testosterone. These effects were prevented by a highly selective CRH antagonist, thus indicating that melatonin does not exert a direct role. Specific mitogen-activated protein kinase kinase (MEK) and jnk blockers inhibited expression of c-jun, c-fos, StAR and the production of testosterone, confirming that these are events triggered downstream of erk and jnk. In Leydig cells from photoperiodically regressed adult hamsters, CRH inhibited the production of androstane-3α,17β-diol (3α-diol), the main androgen produced, through the same signaling pathway. Testicular melatonin concentration was 3-4-fold higher in reproductively inactive hamsters than that detected in active animals. Since melatonin, CRH, and their receptors are present not only in hamster testes but also in testicular biopsies of infertile men, we can conjecture about the relevance of this previously uncharacterized pathway in human fertility disorders. In summary, our study identifies crucial intracellular events triggered by melatonin/CRH in the testis that lead to a down-regulation of the steroidogenic process.
publishDate 2012
dc.date.none.fl_str_mv 2012-08
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/11336/9852
Rossi, Soledad Paola; Matzkin, Maria Eugenia; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; et al.; New insights into melatonin signaling in hamster Leydig cells; Academic Press Inc Elsevier Science; General And Comparative Endocrinology; 178; 1; 8-2012; 153-163
0016-6480
1095-6840
url http://hdl.handle.net/11336/9852
identifier_str_mv Rossi, Soledad Paola; Matzkin, Maria Eugenia; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; et al.; New insights into melatonin signaling in hamster Leydig cells; Academic Press Inc Elsevier Science; General And Comparative Endocrinology; 178; 1; 8-2012; 153-163
0016-6480
1095-6840
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ygcen.2012.04.031
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0016648012001955
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 Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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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