title: Biased signalling in follicle stimulating hormone action.
abstract: Follicle-stimulating hormone (FSH) plays a crucial role in the control of reproduction by specifically binding to and activating a membrane receptor (FSHR) that belongs to the G protein-coupled receptor (GPCR) family. Similar to all GPCRs, FSHR activation mechanisms have generally been viewed as a two-state process connecting a unique FSH-bound active receptor to the Gs/cAMP pathway. Over the last decade, paralleling the breakthroughs that were made in the GPCR field, our understanding of FSH actions at the molecular level has dramatically changed. There are numerous facts indicating that the active FSHR is connected to a complex signalling network rather than the sole Gs/cAMP pathway. Consistently, the FSHR probably exists in equilibrium between multiple conformers, a subset of them being stabilized upon ligand binding. Importantly, the nature of the stabilized conformers of the receptor directly depends on the chemical structure of the ligand bound. This implies that it is possible to selectively control the intracellular signalling pathways activated by using biased ligands. Such biased ligands can be of different nature: small chemical molecules, glycosylation variants of the hormone or antibody/hormone complexes. Likewise, mutations or polymorphisms affecting the FSHR can also lead to stabilization of preferential conformers, hence to selective modulation of signalling pathways. These emerging notions offer a new conceptual framework that could potentially lead to the development of more specific drugs while also improving the way FSHR mutants/variants are functionally characterized.
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, F-37041 Tours, France.
authors.forename: Flavie
authors.initials: F
authors.lastname: Landomiel
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, F-37041 Tours, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gallay
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, F-37041 Tours, France.
authors.forename: Gwenhael
authors.initials: G
authors.lastname: Jégot
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, F-37041 Tours, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Tranchant
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, F-37041 Tours, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Durand
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, F-37041 Tours, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bourquard
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, F-37041 Tours, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Crépieux
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, F-37041 Tours, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Poupon
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS, UMR7247, F-37380 Nouzilly, France; Université François Rabelais, F-37041 Tours, France. Electronic address: Eric.Reiter@tours.inra.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Reiter
mesh_terms: D000818:Animals; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011962:Receptors, FSH / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008024:Ligands; D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone
keywords: FSH; FSHR; GPCR; Gonadotropin; Signalling bias