Artículo
Androgens downregulate anti-Müllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites
Edelsztein, Nadia Yasmín
; Racine, Chrystèle; di Clemente, Nathalie; Schteingart, Helena Fedora
; Rey, Rodolfo Alberto
Fecha de publicación:
12/2018
Editorial:
Society for the Study of Reproduction
Revista:
Biology of Reproduction
ISSN:
0006-3363
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
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Articulos(CEDIE)
Articulos de CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Articulos de CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Citación
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
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