title: Novel pathways in gonadotropin receptor signaling and biased agonism.
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.
authors.affiliation: BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France. aulloaa@servidor.unam.mx
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ulloa-Aguirre
authors.forename: Pascale
authors.initials: P
authors.lastname: Crépieux
authors.forename: Anne
authors.initials: A
authors.lastname: Poupon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Maurel
authors.forename: Eric
authors.initials: E
authors.lastname: Reiter
mesh_terms: D000818:Animals; D054313:Drug Agonism; D005260:Female; D006062:Gonadotropins / Q000819:agonists / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008297:Male; D008954:Models, Biological; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology; D011967:Receptors, Gonadotropin / Q000819:agonists* / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013379:Substrate Specificity
chemical_list: D006062:Gonadotropins; D018796:Immunoconjugates; D008024:Ligands; D011134:Polysaccharides; D011967:Receptors, Gonadotropin