Testosterona inhibe la actividad de la aldosterona sintasa silvestre y quimérica in vitro

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dc.catalogadorvzp
dc.contributor.authorVecchiola Cardenas, Andrea Paola
dc.contributor.authorSaldias Fuentes, Cristóbal Abraham
dc.contributor.authorCarvajal Maldonado, Cristian Andrés
dc.contributor.authorCampino Johnson, María Del Carmen
dc.contributor.authorAllende Sanzana, Fidel Alejandro
dc.contributor.authorTapia-Castillo, Alejandra
dc.contributor.authorLagos, Carlos F.
dc.contributor.authorFardella Bello, Carlos Enrique
dc.date.accessioned2025-02-27T17:32:16Z
dc.date.available2025-02-27T17:32:16Z
dc.date.issued2021
dc.description.abstract© 2021 Sociedad Medica de Santiago. All rights reserved.Background: Familial hyperaldosteronism type I is caused by the generation of a chimeric aldosterone synthase enzyme (ASCE) which is regulated by ACTH instead of angiotensin II. We have reported that in vitro, the wild-type (ASWT) and chimeric aldosterone synthase (ASCE) enzymes are inhibited by progesterone and estradiol does not affect their activity. Aim: To explore the direct action of testosterone on ASWT and ASCE enzymes. Material and Methods: HEK-293 cells were transiently transfected with vectors containing the full ASWT or ASCE cDNAs. The effect of testosterone on AS enzyme activities was evaluated incubating HEK-cells transfected with enzyme vectors and adding deoxycorticosterone (DOC) alone or DOC plus increasing doses of testosterone. Aldosterone production was measured by HPLC-MS/MS. Docking of testosterone within the active sites of both enzymes was performed by modelling in silico. Results: In this system, testosterone inhibited ASWT (90% inhibition at five µM, 50% inhibitory concentration (IC50) =1.690 µM) with higher efficacy and potency than ASCE (80% inhibition at five µM, IC50=3.176 µM). Molecular modelling studies showed different orientation of testosterone in ASWT and ASCE crystal structures. Conclusions: The inhibitory effect of testosterone on ASWT or ASCE enzymes is a novel non-genomic testosterone action, suggesting that further clinical studies are needed to assess the role of testosterone in the screening and diagnosis of primary aldosteronism.
dc.description.funderCentro Traslacional de Endocrinología UC
dc.description.funderComisión Nacional de Investigación Científica y Tecnológica de Chile
dc.description.funderFONDECYT
dc.fechaingreso.objetodigital2025-02-27
dc.format.extent1543
dc.format.extent5 páginas
dc.fuente.origenScopus
dc.identifier.doi10.4067/S0034-98872021001101539
dc.identifier.eissn7176163
dc.identifier.issn0034-9887
dc.identifier.pubmedid35735315
dc.identifier.scopusidSCOPUS_ID:85132225998
dc.identifier.urihttp://dx.doi.org/10.4067/S0034-98872021001101539
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/102278
dc.information.autorucEscuela de Medicina; Vecchiola Cárdenas, Andrea Paola; S/I; 123319
dc.information.autorucEscuela de Medicina; Saldias Fuentes, Cristóbal Abraham; 0000-0003-2626-084X; 205653
dc.information.autorucEscuela de Medicina; Carvajal Maldonado, Cristian Andrés; 0000-0002-0668-412X; 8586
dc.information.autorucEscuela de Medicina; Campino Johnson, María Del Carmen; S/I; 99519
dc.information.autorucEscuela de Medicina; Allende Sanzana, Fidel Alejandro; 0000-0002-6508-4052; 1004550
dc.information.autorucEscuela de Medicina; Fardella Bello, Carlos Enrique; 0000-0002-5500-4434; 66235
dc.issue.numero11
dc.language.isoes
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final1543
dc.pagina.inicio1539
dc.publisherSociedad Medica de Santiago
dc.relation.ispartofRevista Medica de Chile
dc.revistaRevista Medica de Chile
dc.rightsacceso abierto
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.en
dc.subjectCytochrome P-450 CYP11B2
dc.subjectHEK293 Cells, Testosterone
dc.subjectCytochrome P-450 CYP11B2
dc.subjectHEK293 Cells
dc.subjectTestosterone
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleTestosterona inhibe la actividad de la aldosterona sintasa silvestre y quimérica in vitro
dc.title.alternativeTestosterone inhibits human wild-type and chimeric aldosterone synthase activity in vitro
dc.typeartículo
dc.volumen149
sipa.codpersvinculados123319
sipa.codpersvinculados205653
sipa.codpersvinculados8586
sipa.codpersvinculados99519
sipa.codpersvinculados1004550
sipa.codpersvinculados66235
sipa.trazabilidadSCOPUS;2022-07-08
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