2. Academic Validation
  3. Human Luteinizing Hormone and Chorionic Gonadotropin Display Biased Agonism at the LH and LH/CG Receptors

Human Luteinizing Hormone and Chorionic Gonadotropin Display Biased Agonism at the LH and LH/CG Receptors

  • Sci Rep. 2017 Apr 19;7(1):940. doi: 10.1038/s41598-017-01078-8.
Laura Riccetti 1,  Romain Yvinec 2,  Danièle Klett 2,  Nathalie Gallay 2,  Yves Combarnous 2,  Eric Reiter 3,  Manuela Simoni 1 4 5,  Livio Casarini 6 7,  Mohammed Akli Ayoub 8 9 10
Affiliations

Affiliations

  • 1 Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
  • 2 PRC, INRA, CNRS, Université François Rabelais-Tours, 37380, Nouzilly, France.
  • 3 PRC, INRA, CNRS, Université François Rabelais-Tours, 37380, Nouzilly, France. Eric.Reiter@inra.fr.
  • 4 Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy.
  • 5 Azienda, Ospedaliero-Universitaria di Modena, Modena, Italy.
  • 6 Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. livio.casarini@unimore.it.
  • 7 Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy. livio.casarini@unimore.it.
  • 8 PRC, INRA, CNRS, Université François Rabelais-Tours, 37380, Nouzilly, France. mayoub@uaeu.ac.ae.
  • 9 LE STUDIUM® Loire Valley Institute for Advanced Studies, 45000, Orléans, France. mayoub@uaeu.ac.ae.
  • 10 Biology Department, College of Science, United Arab Emirates University, 15551, Al Ain, United Arab Emirates. mayoub@uaeu.ac.ae.
PMID: 28424471 DOI: 10.1038/s41598-017-01078-8
Abstract

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.

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