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Novel pathways in gonadotropin receptor signaling and biased agonism

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Abstract

Gonadotropins play a central role in the control of male and female reproduction. Selective agonists and antagonists of gonadotropin receptors would be of great interest for the treatment of infertility or as non steroidal contraceptive. However, to date, only native hormones are being used in assisted reproduction technologies as there is no pharmacological agent available to manipulate gonadotropin receptors. Over the last decade, there has been a growing perception of the complexity associated with gonadotropin receptors’ cellular signaling. It is now clear that the Gs/cAMP/PKA pathway is not the sole mechanism that must be taken into account in order to understand these hormones’ biological actions. In parallel, consistent with the emerging paradigm of biased agonism, several examples of ligand-mediated selective signaling pathway activation by gonadotropin receptors have been reported. Small molecule ligands, modulating antibodies interacting with the hormones and glycosylation variants of the native glycoproteins have all demonstrated their potential to trigger such selective signaling. Altogether, the available data and emerging concepts give rise to intriguing opportunities towards a more efficient control of reproductive function and associated disorders.

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Acknowledgements

This work was supported by the Action d’Envergure (AE) INRIA/INRA Regate, and Region Centre project. BIOS group is a young research team from INRA. Alfredo Ulloa-Aguirre is recipient of a Research Career Development Award from the Fundación IMSS, México and is supported by grant 86881 from CONACyT, Mexico. Eric Reiter and Alfredo Ulloa-Aguirre are members of Le Studium Consortium for Research and Training in Reproductive Sciences (sCORTS), Orléans, France.

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  1. BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, 37380, Nouzilly, France

    Alfredo Ulloa-Aguirre, Pascale Crépieux, Anne Poupon, Marie-Christine Maurel & Eric Reiter

  2. CNRS, UMR6175, 37380, Nouzilly, France

    Alfredo Ulloa-Aguirre, Pascale Crépieux, Anne Poupon, Marie-Christine Maurel & Eric Reiter

  3. Université François Rabelais, 37041, Tours, France

    Alfredo Ulloa-Aguirre, Pascale Crépieux, Anne Poupon, Marie-Christine Maurel & Eric Reiter

  4. IFCE, 37380, Nouzilly, France

    Alfredo Ulloa-Aguirre, Pascale Crépieux, Anne Poupon, Marie-Christine Maurel & Eric Reiter

  5. LE STUDIUM Institute for Advanced Studies, Orléans, France

    Alfredo Ulloa-Aguirre

  6. Research Unit in Reproductive Medicine, UMAE Hospital de Ginecobstetricia “Luis Castelazo Ayala”, IMSS, México, DF, Mexico

    Alfredo Ulloa-Aguirre

  7. Apdo. Postal 99–065, Unidad Independencia, C.P. 10101, México, DF, Mexico

    Alfredo Ulloa-Aguirre

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  1. Alfredo Ulloa-Aguirre
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Ulloa-Aguirre, A., Crépieux, P., Poupon, A. et al. Novel pathways in gonadotropin receptor signaling and biased agonism. Rev Endocr Metab Disord 12, 259–274 (2011). https://doi.org/10.1007/s11154-011-9176-2

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