Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development

Autores
Edelsztein, Nadia Yasmín; Schteingart, Helena Fedora; Rey, Rodolfo Alberto
Año de publicación
2019
Idioma
español castellano
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Androgen-dependent maturation ofSertoli cells during postnatal testicular development is key for the establishmentof spermatogenesis. Meiosis in the male begins at puberty and relies onandrogens and retinoic acid. Immature Sertoli cells produce high levels of AMH,which is inhibited by androgens at puberty. The molecular mechanisms underlyingandrogen-mediated AMH decline are unknown. CYP26B1 degrades retinoic acid inthe prenatal testis preventing meiosis initiation. The concurrence of meioticentry and Sertoli cell maturation in response to androgens led us to proposethat CYP26B1 ?like AMH? is downregulated by androgens in the Sertoli cellduring puberty, thus enabling meiosis initiation. By immunohistochemistry, wesaw that CYP26B1 expression declines in the postnatal mouse Sertoli cell asandrogen receptor (AR) expression increases, closely before meioticspermatocytes appear. Luciferase reporter assays in the SMAT1 Sertoli cell lineshowed a direct negative effect on Amh promoter activity in the presence ofdihydrotestosterone (DHT, P<0.001). Site-directed mutagenesis and ChIP-qPCRassays showed that androgen-mediated inhibition requires the SF1 sites in theAmh promoter. Regarding Cyp26b1, we saw no changes in promoter activity inresponse to androgens (P=0.34). This lack of response was further supported byinvariant levels of endogenous Cyp26b1 expression in SMAT1 cells transfectedwith the AR (P=1.0) and in primary Sertoli cells of 10-day-old mice in culture(P=0.7), after DHT treatment. ChIP-qPCR showed no enrichment in AR sequencesanalyzed, indicating a lack of functional binding of the AR. In sum, weconfirmed a negative correlation between the immature Sertoli cell markers AMHand CYP26B1 and AR expression and meiotic initiation in postnatal development.We identified the molecular mechanism underlying AMH inhibition by androgensbut found that the decline in CYP26B1 expression is not caused by a directinhibitory androgen effect on Sertoli cells.
Fil: Edelsztein, Nadia Yasmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Schteingart, Helena Fedora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Asociación Argentina de Nanomedicinas
Materia
Sertoli
androgens
meiosis
AMH
Cyp26b1
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:11336/238979
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/238979
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal developmentEdelsztein, Nadia YasmínSchteingart, Helena FedoraRey, Rodolfo AlbertoSertoliandrogensmeiosisAMHCyp26b1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Androgen-dependent maturation ofSertoli cells during postnatal testicular development is key for the establishmentof spermatogenesis. Meiosis in the male begins at puberty and relies onandrogens and retinoic acid. Immature Sertoli cells produce high levels of AMH,which is inhibited by androgens at puberty. The molecular mechanisms underlyingandrogen-mediated AMH decline are unknown. CYP26B1 degrades retinoic acid inthe prenatal testis preventing meiosis initiation. The concurrence of meioticentry and Sertoli cell maturation in response to androgens led us to proposethat CYP26B1 ?like AMH? is downregulated by androgens in the Sertoli cellduring puberty, thus enabling meiosis initiation. By immunohistochemistry, wesaw that CYP26B1 expression declines in the postnatal mouse Sertoli cell asandrogen receptor (AR) expression increases, closely before meioticspermatocytes appear. Luciferase reporter assays in the SMAT1 Sertoli cell lineshowed a direct negative effect on Amh promoter activity in the presence ofdihydrotestosterone (DHT, P<0.001). Site-directed mutagenesis and ChIP-qPCRassays showed that androgen-mediated inhibition requires the SF1 sites in theAmh promoter. Regarding Cyp26b1, we saw no changes in promoter activity inresponse to androgens (P=0.34). This lack of response was further supported byinvariant levels of endogenous Cyp26b1 expression in SMAT1 cells transfectedwith the AR (P=1.0) and in primary Sertoli cells of 10-day-old mice in culture(P=0.7), after DHT treatment. ChIP-qPCR showed no enrichment in AR sequencesanalyzed, indicating a lack of functional binding of the AR. In sum, weconfirmed a negative correlation between the immature Sertoli cell markers AMHand CYP26B1 and AR expression and meiotic initiation in postnatal development.We identified the molecular mechanism underlying AMH inhibition by androgensbut found that the decline in CYP26B1 expression is not caused by a directinhibitory androgen effect on Sertoli cells.Fil: Edelsztein, Nadia Yasmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Schteingart, Helena Fedora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioAsociación Argentina de NanomedicinasFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/238979Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 59-590025-76801669-9106CONICET DigitalCONICETspainfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2010-a-2019/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:32:09Zoai:ri.conicet.gov.ar:11336/238979instacron: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:34982025-10-15 15:32:09.505CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development
title Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development
spellingShingle Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development
Edelsztein, Nadia Yasmín
Sertoli
androgens
meiosis
AMH
Cyp26b1
title_short Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development
title_full Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development
title_fullStr Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development
title_full_unstemmed Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development
title_sort Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development
dc.creator.none.fl_str_mv Edelsztein, Nadia Yasmín
Schteingart, Helena Fedora
Rey, Rodolfo Alberto
author Edelsztein, Nadia Yasmín
author_facet Edelsztein, Nadia Yasmín
Schteingart, Helena Fedora
Rey, Rodolfo Alberto
author_role author
author2 Schteingart, Helena Fedora
Rey, Rodolfo Alberto
author2_role author
author
dc.subject.none.fl_str_mv Sertoli
androgens
meiosis
AMH
Cyp26b1
topic Sertoli
androgens
meiosis
AMH
Cyp26b1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Androgen-dependent maturation ofSertoli cells during postnatal testicular development is key for the establishmentof spermatogenesis. Meiosis in the male begins at puberty and relies onandrogens and retinoic acid. Immature Sertoli cells produce high levels of AMH,which is inhibited by androgens at puberty. The molecular mechanisms underlyingandrogen-mediated AMH decline are unknown. CYP26B1 degrades retinoic acid inthe prenatal testis preventing meiosis initiation. The concurrence of meioticentry and Sertoli cell maturation in response to androgens led us to proposethat CYP26B1 ?like AMH? is downregulated by androgens in the Sertoli cellduring puberty, thus enabling meiosis initiation. By immunohistochemistry, wesaw that CYP26B1 expression declines in the postnatal mouse Sertoli cell asandrogen receptor (AR) expression increases, closely before meioticspermatocytes appear. Luciferase reporter assays in the SMAT1 Sertoli cell lineshowed a direct negative effect on Amh promoter activity in the presence ofdihydrotestosterone (DHT, P<0.001). Site-directed mutagenesis and ChIP-qPCRassays showed that androgen-mediated inhibition requires the SF1 sites in theAmh promoter. Regarding Cyp26b1, we saw no changes in promoter activity inresponse to androgens (P=0.34). This lack of response was further supported byinvariant levels of endogenous Cyp26b1 expression in SMAT1 cells transfectedwith the AR (P=1.0) and in primary Sertoli cells of 10-day-old mice in culture(P=0.7), after DHT treatment. ChIP-qPCR showed no enrichment in AR sequencesanalyzed, indicating a lack of functional binding of the AR. In sum, weconfirmed a negative correlation between the immature Sertoli cell markers AMHand CYP26B1 and AR expression and meiotic initiation in postnatal development.We identified the molecular mechanism underlying AMH inhibition by androgensbut found that the decline in CYP26B1 expression is not caused by a directinhibitory androgen effect on Sertoli cells.
Fil: Edelsztein, Nadia Yasmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Schteingart, Helena Fedora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Asociación Argentina de Nanomedicinas
description Androgen-dependent maturation ofSertoli cells during postnatal testicular development is key for the establishmentof spermatogenesis. Meiosis in the male begins at puberty and relies onandrogens and retinoic acid. Immature Sertoli cells produce high levels of AMH,which is inhibited by androgens at puberty. The molecular mechanisms underlyingandrogen-mediated AMH decline are unknown. CYP26B1 degrades retinoic acid inthe prenatal testis preventing meiosis initiation. The concurrence of meioticentry and Sertoli cell maturation in response to androgens led us to proposethat CYP26B1 ?like AMH? is downregulated by androgens in the Sertoli cellduring puberty, thus enabling meiosis initiation. By immunohistochemistry, wesaw that CYP26B1 expression declines in the postnatal mouse Sertoli cell asandrogen receptor (AR) expression increases, closely before meioticspermatocytes appear. Luciferase reporter assays in the SMAT1 Sertoli cell lineshowed a direct negative effect on Amh promoter activity in the presence ofdihydrotestosterone (DHT, P<0.001). Site-directed mutagenesis and ChIP-qPCRassays showed that androgen-mediated inhibition requires the SF1 sites in theAmh promoter. Regarding Cyp26b1, we saw no changes in promoter activity inresponse to androgens (P=0.34). This lack of response was further supported byinvariant levels of endogenous Cyp26b1 expression in SMAT1 cells transfectedwith the AR (P=1.0) and in primary Sertoli cells of 10-day-old mice in culture(P=0.7), after DHT treatment. ChIP-qPCR showed no enrichment in AR sequencesanalyzed, indicating a lack of functional binding of the AR. In sum, weconfirmed a negative correlation between the immature Sertoli cell markers AMHand CYP26B1 and AR expression and meiotic initiation in postnatal development.We identified the molecular mechanism underlying AMH inhibition by androgensbut found that the decline in CYP26B1 expression is not caused by a directinhibitory androgen effect on Sertoli cells.
publishDate 2019
dc.date.none.fl_str_mv 2019
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/238979
Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 59-59
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/238979
identifier_str_mv Regulatory mechanisms underlying functional maturation of Sertoli cells in response to androgens during postnatal development; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 59-59
0025-7680
1669-9106
CONICET Digital
CONICET
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language spa
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2010-a-2019/
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publisher.none.fl_str_mv Fundación Revista Medicina
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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