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The ERK-dependent signalling is stage-specifically modulated by FSH, during primary Sertoli cell maturation

Oncogene volume 20, pages 4696–4709 (2001)Cite this article

Abstract

Primary cultures of Sertoli cells provide an interesting model to study how signalling pathways induced by a single hormone in a single cell type evolve, depending on the developmental stage. In vivo, follicle-stimulating hormone (FSH) induces proliferation of Sertoli cells in neonate and controls the subsequent differentiation of the entire population. Molecular mechanisms underlying Sertoli cell pleiotropic responses to FSH have long been investigated. But to date, only cAMP-dependent kinase (PKA) activation has been reported to account for most FSH biological activities in male. Here, we demonstrate that FSH activates the ERK MAP kinase pathway following dual coupling of the FSH-R both to Gs and to Gi heterotrimeric proteins, in a PKA- and also Src-dependent manner. This activation is required for FSH-induced proliferation of Sertoli cells isolated 5 days after birth. Consistently, we show that the ERK-mediated FSH mitogenic effect triggers upregulation of cyclin D1. In sharp contrast, at 19 days after birth, as cells proceed through their differentiation program, the ERK pathway is dramatically inhibited by FSH treatment. Taken together, these results show that FSH can exert opposite effects on the ERK signalling cascade during the maturation process of Sertoli cells. Thus, signalling modules triggered by the FSH-R evolve dynamically throughout development of FSH natural target cells.

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Acknowledgements

The authors would like to thank Dr Pierre Savatier (Ecole Normale Supérieure de Lyon, France) for providing anti-cyclin D1 antibodies. We are indebted to Drs Yves Combarnous (Nouzilly) and Jean Closset (Université de Liège, Belgique) for their generous gift of purified porcine FSH. We also acknowlegde the technical assistance of the ratcare staff. P Crépieux is a recipient of a fellowship from the ‘Société de Secours des Amis des Sciences’ and from the ‘Fondation d’Aide à la Recherche Organon’. S Marion is funded by a fellowship from the ‘Région Centre’. and the ‘Institut National de la Recherche Agronomique’. This work was funded by the ‘Ligue contre le Cancer’.

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Authors and Affiliations

  1. Laboratoire de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique/Centre National pour la Recherche Scientifique/Université de Tours, UMR 6073, Nouzilly, France

    Pascale Crépieux, Sébastien Marion, Nadine Martinat, Florian Guillou & Eric Reiter

  2. Laboratoire de Pathologie aviaire et Parasitologie, Centre de Recherches de Tours, 37380

    Yves Le Vern & Dominique Kerboeuf

  3. CNRS FRE 2353, Institut de Biologie de Lille, Institut Pasteur de Lille, Lille, 59021, France

    Véronique Fafeur

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  1. Pascale Crépieux
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Correspondence to Pascale Crépieux.

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Crépieux, P., Marion, S., Martinat, N. et al. The ERK-dependent signalling is stage-specifically modulated by FSH, during primary Sertoli cell maturation. Oncogene 20, 4696–4709 (2001). https://doi.org/10.1038/sj.onc.1204632

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