Journal
BIOLOGY OF REPRODUCTION
Volume 99, Issue 6, Pages 1303-1312Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioy152
Keywords
testis; inhibition; testosterone; transcriptional regulation; steroid hormones/steroid hormone receptors; puberty
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Funding
- Fondo Nacional de Promocion Cientifica y Tecnologica (FONCYT), Argentina [PICT 2012-0441]
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Argentina [PIP 11220120100279CO]
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Testicular anti-Mullerian 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
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