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Role of type I receptors for anti-Müllerian hormone in the SMAT-1 Sertoli cell line

Oncogene volume 24, pages 4984–4992 (2005)Cite this article

Abstract

Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-β family responsible for regression of Müllerian ducts during male sexual differentiation and for regulation of gonadal steroidogenesis. AMH is also a gonadal tumor suppressor which mediates its effects through a specific type II receptor and the bone morphogenetic protein (BMP)-specific Smad proteins, suggesting that AMH and BMPs could also share type I receptors, namely activin-like kinases (ALKs)2, 3 or 6. However, attempts to identify a unique AMH type I receptor among them were unsuccessful. Here, using kinase-deficient type I receptors and small interfering RNA technology, we demonstrate that, in an AMH Sertoli target cell line, ALK3 mediates AMH effects on both Smad1 activation and P450 side-chain cleavage enzyme. In addition, transfecting a combination of normal and kinase-deficient receptors, we show that ALK2 can compensate for the absence of ALK3 and probably acts in synergy with ALK3 at high concentrations of AMH to activate Smad1, whereas ALK6 has a competitive inhibitory effect. These results are a first step in understanding how AMH transduces its effects in immature Sertoli cells.

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Acknowledgements

We thank Drs J Massagué, A Atfi, G Rawadi and S Maheswaran for kindly providing DNA constructs. We are grateful to Nathalie Ledée and Sylvie Dubanchet for advice on real-time PCR. We are grateful to the Association pour la Recherche sur le Cancer for its generous support to Nathalie di Clemente (grant no. 4253).

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  1. Institut National de la Santé et de la Recherche Médicale, Unité 493 sur l'Endocrinologie du Développement, Université Paris XI, 32 rue des Carnets, Clamart, 92140, France

    Corinne Belville, Soazik P Jamin, Jean-Yves Picard, Nathalie Josso & Nathalie di Clemente

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  1. Corinne Belville
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  2. Soazik P Jamin
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  3. Jean-Yves Picard
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  4. Nathalie Josso
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Correspondence to Nathalie di Clemente.

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Belville, C., Jamin, S., Picard, JY. et al. Role of type I receptors for anti-Müllerian hormone in the SMAT-1 Sertoli cell line. Oncogene 24, 4984–4992 (2005). https://doi.org/10.1038/sj.onc.1208686

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