Human Luteinizing Hormone and Chorionic Gonadotropin Display Biased Agonism at the LH and LH/CG Receptors
| Autor: | Riccetti, Laura, Yvinec, Romain, Klett, Danièle, Langonné, Nathalie, Combarnous, Yves, Reiter, Eric, Simoni, Manuela, Casarini, Livio, Ayoub, Mohammed Akli |
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| Přispěvatelé: | Università degli Studi di Modena e Reggio Emilia (UNIMORE), 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]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Le Studium - Loire Valley Institute for Advanced Studies, Région Centre ARD2020 Biomédicaments, Associazione Scientifica in Endocrinologia, Andrologia e Metabolismo, LE STUDIUM® Loire Valley Institute for Advanced Studies and AgreenSkills Plus, European Project: 609398,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,AGREENSKILLSPLUS(2014), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), 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) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
steroidogenesis
[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] Science Molecular Networks (q-bio.MN) récepteur hormonal beta arrestine Article Mice steroidogénèse Cyclic AMP Animals Humans chorionic gonadotropin Quantitative Biology - Molecular Networks signal intracellulaire hormonal receptor Progesterone gonadotrophine chorionique Luteinizing Hormone Receptors LH Recombinant Proteins HEK293 Cells beta-Arrestin 1 FOS: Biological sciences Medicine hormone recombinante Autre (Sciences du Vivant) |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.1-11. ⟨10.1038/s41598-017-01078-8⟩ Scientific Reports 1 (7), 1-11. (2017) Scientific Reports, 2017, 7 (1), pp.1-11. ⟨10.1038/s41598-017-01078-8⟩ Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-01078-8⟩ |
| Popis: | Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) have been considered biologically equivalent because of their structural similarities and their binding to the same receptor; the LH/CGR. However, accumulating evidence suggest that LH/CGR differentially responds to the two hormones triggering differential intracellular signaling and steroidogenesis. The mechanistic basis of such differential responses remains mostly unknown. Here, we compared the abilities of recombinant rhLH and rhCG to elicit cAMP, β-arrestin 2 activation, and steroidogenesis in HEK293 cells and mouse Leydig tumor cells (mLTC-1). For this, BRET and FRET technologies were used allowing quantitative analyses of hormone activities in real-time and in living cells. Our data indicate that rhLH and rhCG differentially promote cell responses mediated by LH/CGR revealing interesting divergences in their potencies, efficacies and kinetics: rhCG was more potent than rhLH in both HEK293 and mLTC-1 cells. Interestingly, partial effects of rhLH were found on β-arrestin recruitment and on progesterone production compared to rhCG. Such a link was further supported by knockdown experiments. These pharmacological differences demonstrate that rhLH and rhCG act as natural biased agonists. The discovery of novel mechanisms associated with gonadotropin-specific action may ultimately help improve and personalize assisted reproduction technologies. |
| Databáze: | OpenAIRE |
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