Novel pathways in gonadotropin receptor signaling and biased agonism
2011
Ulloa-Aguirre, Alfredo | Crépieux, Pascale | Poupon, Anne | Maurel, Marie-Christine | Reiter, Eric | Physiologie de la reproduction et des comportements [Nouzilly] (PRC) ; Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS) | 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 Fundacion IMSS, Mexico 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), Orleans, France.
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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