Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites

Autores
Edelsztein, Nadia Yasmín; Racine, Chrystèle; di Clemente, Nathalie; Schteingart, Helena Fedora; Rey, Rodolfo Alberto
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Testicular anti-Müllerian hormone (AMH) production is inhibited by androgens around pubertal onset, as observed under normal physiological conditions and in patients with precocious puberty. In agreement, AMH downregulation is absent in patients with androgen insensitivity. The molecular mechanisms underlying the negative regulation of AMH by androgens remain unknown. Our aim was to elucidate the mechanisms through which androgens downregulate AMH expression in the testis. A direct negative effect of androgens on the transcriptional activity of the AMH promoter was found using luciferase reporter assays in the mouse prepubertal Sertoli cell line SMAT1. A strong inhibition of AMH promoter activity was seen in the presence of both testosterone and DHT and of the androgen receptor. By site-directed mutagenesis and chromatin immunoprecipitation assays, we showed that androgen-mediated inhibition involved the binding sites for steroidogenic factor 1 (SF1) present in the proximal promoter of the AMH gene. In this study, we describe for the first time the mechanism behind AMH inhibition by androgens, as seen in physiological and pathological conditions in males. Inhibition of AMH promoter activity by androgens could be due to protein-protein interactions between the ligand-bound androgen receptor and SF1 or by blockage of SF1 binding to its sites on the AMH promoter.
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: Racine, Chrystèle. Inserm; Francia
Fil: di Clemente, Nathalie. Inserm; Francia
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
Materia
INHIBITION
PUBERTY
STEROID HORMONES/STEROID HORMONE RECEPTORS
TESTIS
TESTOSTERONE
TRANSCRIPTIONAL REGULATION
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:11336/90864
Acceder
id CONICETDig_fb52b1de5a284a6fe7e058db0efa7a97
oai_identifier_str oai:ri.conicet.gov.ar:11336/90864
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sitesEdelsztein, Nadia YasmínRacine, Chrystèledi Clemente, NathalieSchteingart, Helena FedoraRey, Rodolfo AlbertoINHIBITIONPUBERTYSTEROID HORMONES/STEROID HORMONE RECEPTORSTESTISTESTOSTERONETRANSCRIPTIONAL REGULATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Testicular anti-Müllerian hormone (AMH) production is inhibited by androgens around pubertal onset, as observed under normal physiological conditions and in patients with precocious puberty. In agreement, AMH downregulation is absent in patients with androgen insensitivity. The molecular mechanisms underlying the negative regulation of AMH by androgens remain unknown. Our aim was to elucidate the mechanisms through which androgens downregulate AMH expression in the testis. A direct negative effect of androgens on the transcriptional activity of the AMH promoter was found using luciferase reporter assays in the mouse prepubertal Sertoli cell line SMAT1. A strong inhibition of AMH promoter activity was seen in the presence of both testosterone and DHT and of the androgen receptor. By site-directed mutagenesis and chromatin immunoprecipitation assays, we showed that androgen-mediated inhibition involved the binding sites for steroidogenic factor 1 (SF1) present in the proximal promoter of the AMH gene. In this study, we describe for the first time the mechanism behind AMH inhibition by androgens, as seen in physiological and pathological conditions in males. Inhibition of AMH promoter activity by androgens could be due to protein-protein interactions between the ligand-bound androgen receptor and SF1 or by blockage of SF1 binding to its sites on the AMH promoter.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: Racine, Chrystèle. Inserm; FranciaFil: di Clemente, Nathalie. Inserm; FranciaFil: 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"; ArgentinaSociety for the Study of Reproduction2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/90864Edelsztein, Nadia Yasmín; Racine, Chrystèle; di Clemente, Nathalie; Schteingart, Helena Fedora; Rey, Rodolfo Alberto; Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites; Society for the Study of Reproduction; Biology of Reproduction; 99; 6; 12-2018; 1303-13120006-3363CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/biolre/ioy152info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biolreprod/article-abstract/99/6/1303/5050366info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:19Zoai:ri.conicet.gov.ar:11336/90864instacron: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:34982025-09-03 09:52:19.696CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites
title Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites
spellingShingle Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites
Edelsztein, Nadia Yasmín
INHIBITION
PUBERTY
STEROID HORMONES/STEROID HORMONE RECEPTORS
TESTIS
TESTOSTERONE
TRANSCRIPTIONAL REGULATION
title_short Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites
title_full Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites
title_fullStr Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites
title_full_unstemmed Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites
title_sort Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites
dc.creator.none.fl_str_mv Edelsztein, Nadia Yasmín
Racine, Chrystèle
di Clemente, Nathalie
Schteingart, Helena Fedora
Rey, Rodolfo Alberto
author Edelsztein, Nadia Yasmín
author_facet Edelsztein, Nadia Yasmín
Racine, Chrystèle
di Clemente, Nathalie
Schteingart, Helena Fedora
Rey, Rodolfo Alberto
author_role author
author2 Racine, Chrystèle
di Clemente, Nathalie
Schteingart, Helena Fedora
Rey, Rodolfo Alberto
author2_role author
author
author
author
dc.subject.none.fl_str_mv INHIBITION
PUBERTY
STEROID HORMONES/STEROID HORMONE RECEPTORS
TESTIS
TESTOSTERONE
TRANSCRIPTIONAL REGULATION
topic INHIBITION
PUBERTY
STEROID HORMONES/STEROID HORMONE RECEPTORS
TESTIS
TESTOSTERONE
TRANSCRIPTIONAL REGULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Testicular anti-Müllerian hormone (AMH) production is inhibited by androgens around pubertal onset, as observed under normal physiological conditions and in patients with precocious puberty. In agreement, AMH downregulation is absent in patients with androgen insensitivity. The molecular mechanisms underlying the negative regulation of AMH by androgens remain unknown. Our aim was to elucidate the mechanisms through which androgens downregulate AMH expression in the testis. A direct negative effect of androgens on the transcriptional activity of the AMH promoter was found using luciferase reporter assays in the mouse prepubertal Sertoli cell line SMAT1. A strong inhibition of AMH promoter activity was seen in the presence of both testosterone and DHT and of the androgen receptor. By site-directed mutagenesis and chromatin immunoprecipitation assays, we showed that androgen-mediated inhibition involved the binding sites for steroidogenic factor 1 (SF1) present in the proximal promoter of the AMH gene. In this study, we describe for the first time the mechanism behind AMH inhibition by androgens, as seen in physiological and pathological conditions in males. Inhibition of AMH promoter activity by androgens could be due to protein-protein interactions between the ligand-bound androgen receptor and SF1 or by blockage of SF1 binding to its sites on the AMH promoter.
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: Racine, Chrystèle. Inserm; Francia
Fil: di Clemente, Nathalie. Inserm; Francia
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
description Testicular anti-Müllerian hormone (AMH) production is inhibited by androgens around pubertal onset, as observed under normal physiological conditions and in patients with precocious puberty. In agreement, AMH downregulation is absent in patients with androgen insensitivity. The molecular mechanisms underlying the negative regulation of AMH by androgens remain unknown. Our aim was to elucidate the mechanisms through which androgens downregulate AMH expression in the testis. A direct negative effect of androgens on the transcriptional activity of the AMH promoter was found using luciferase reporter assays in the mouse prepubertal Sertoli cell line SMAT1. A strong inhibition of AMH promoter activity was seen in the presence of both testosterone and DHT and of the androgen receptor. By site-directed mutagenesis and chromatin immunoprecipitation assays, we showed that androgen-mediated inhibition involved the binding sites for steroidogenic factor 1 (SF1) present in the proximal promoter of the AMH gene. In this study, we describe for the first time the mechanism behind AMH inhibition by androgens, as seen in physiological and pathological conditions in males. Inhibition of AMH promoter activity by androgens could be due to protein-protein interactions between the ligand-bound androgen receptor and SF1 or by blockage of SF1 binding to its sites on the AMH promoter.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/11336/90864
Edelsztein, Nadia Yasmín; Racine, Chrystèle; di Clemente, Nathalie; Schteingart, Helena Fedora; Rey, Rodolfo Alberto; Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites; Society for the Study of Reproduction; Biology of Reproduction; 99; 6; 12-2018; 1303-1312
0006-3363
CONICET Digital
CONICET
url http://hdl.handle.net/11336/90864
identifier_str_mv Edelsztein, Nadia Yasmín; Racine, Chrystèle; di Clemente, Nathalie; Schteingart, Helena Fedora; Rey, Rodolfo Alberto; Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites; Society for the Study of Reproduction; Biology of Reproduction; 99; 6; 12-2018; 1303-1312
0006-3363
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/biolre/ioy152
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biolreprod/article-abstract/99/6/1303/5050366
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
dc.publisher.none.fl_str_mv Society for the Study of Reproduction
publisher.none.fl_str_mv Society for the Study of Reproduction
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_ 1842269150894882816
score 13.13397

Publicaciones similares