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dc.contributor.author Brion, Laura
dc.contributor.author Maloberti, Paula Mariana
dc.contributor.author Gómez, Natalia
dc.contributor.author Poderoso, Cecilia
dc.contributor.author Gorostizaga, Alejandra Beatriz
dc.contributor.author Mori Sequeiros, María de Las Mercedes
dc.contributor.author Acquier, Andrea Beatriz
dc.contributor.author Cooke, Mariana
dc.contributor.author Mendez, Carlos Fernando
dc.contributor.author Podesta, Ernesto Jorge
dc.contributor.author Paz, Cristina del Valle
dc.date.available 2017-04-17T21:57:15Z
dc.date.issued 2011-07
dc.identifier.citation Brion, Laura; Maloberti, Paula Mariana; Gómez, Natalia; Poderoso, Cecilia; Gorostizaga, Alejandra Beatriz; et al.; MAPK phosphatase-1 (MKP-1) expression is up-regulated by hCG/cAMP and modulates steroidogenesis in MA-10 Leydig cells; Oxford University Press; Endocrinology; 152; 7; 7-2011; 2665-2677
dc.identifier.issn 0013-7227
dc.identifier.uri http://hdl.handle.net/11336/15349
dc.description.abstract MAP kinases (MAPKs), such as ERK1/2, exert profound effects on a variety of physiological processes. In steroidogenic cells, ERK1/2 are involved in the expression and activation of steroidogenic acute regulatory protein, which plays a central role in the regulation of steroidogenesis. In MA-10 Leydig cells, LH and chorionic gonadotropin (CG) trigger transient ERK1/2 activation via protein kinase A, although the events that lead to ERK1/2 inactivation are not fully described. Here, we describe the hormonal regulation of MAPK phosphatase-1 (MKP-1), an enzyme that inactivates MAPKs, in MA-10 cells. In our experiments, human CG (hCG)/cAMP stimulation rapidly and transiently increased MKP-1 mRNA levels by a transcriptional action. This effect was accompanied by an increase in protein levels in both nuclear and mitochondrial compartments. In cells transiently expressing flag-MKP-1 protein, hCG/cAMP promoted the accumulation of the recombinant protein in a time-dependent manner (10-fold at 1 h). Moreover, hCG/cAMP triggered ERK1/2-dependent MKP-1 phosphorylation. The blockade of cAMP-induced MAPK kinase/ERK activation abated MKP-1 phosphorylation but only partially reduced flag-MKP-1 protein accumulation. Together, these results suggest that hCG regulates MKP-1 at transcriptional and posttranslational level, protein phosphorylation being one of the mechanisms involved in this regulation. Our study also demonstrates that MKP-1 overexpression reduces the effects of cAMP on ERK1/2 phosphorylation, steroidogenic acute regulatory gene promoter activity, mRNA levels, and steroidogenesis, whereas MKP-1 down-regulation by small interfering RNA produces opposite effects. In summary, our data demonstrate that hCG regulates MKP-1 expression at multiple stages as a negative feedback regulatory mechanism to modulate the hormonal action on ERK1/2 activity and steroidogenesis.
dc.format application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject hCG
dc.subject MAP Kinase Phosphatase-1
dc.subject MA-10 Leydig cells
dc.subject ERK 1/2
dc.subject Steroidogenesis
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title MAPK phosphatase-1 (MKP-1) expression is up-regulated by hCG/cAMP and modulates steroidogenesis in MA-10 Leydig cells
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-04-07T14:28:07Z
dc.identifier.eissn 1945-7170
dc.journal.volume 152
dc.journal.number 7
dc.journal.pagination 2665-2677
dc.journal.pais Estados Unidos
dc.journal.ciudad Oxford
dc.description.fil Fil: Brion, Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Maloberti, Paula Mariana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Gómez, Natalia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Poderoso, Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Gorostizaga, Alejandra Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Mori Sequeiros, María de Las Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Acquier, Andrea Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Cooke, Mariana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Mendez, Carlos Fernando. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Podesta, Ernesto Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Paz, Cristina del Valle. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title Endocrinology
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1210/en.2011-0021
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2011-0021


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)