Departamento de Ecología y Recursos Naturales, Biología, Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico
Yeu-Farn Lin
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada
Yiming Cui
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada
Ying Wang
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada
Dominic Devost
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada
Ferdinand Roelfsema
Department of Internal Medicine, Section Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, Netherlands
Frederik Steyn
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Australia; Department of Neurology, Royal Brisbane & Women's Hospital, Queensland, London, United Kingdom
Departamento de Ecología y Recursos Naturales, Biología, Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico
Derek Boerboom
Département de biomédecine vétérinaire, Université de Montréal, Ste-Hyacinthe, Canada
Gonadotropin-releasing hormone (GnRH) is the primary neuropeptide controlling reproduction in vertebrates. GnRH stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis via a G-protein-coupled receptor, GnRHR, in the pituitary gland. In mammals, GnRHR lacks a C-terminal cytosolic tail (Ctail) and does not exhibit homologous desensitization. This might be an evolutionary adaptation that enables LH surge generation and ovulation. To test this idea, we fused the chicken GnRHR Ctail to the endogenous murine GnRHR in a transgenic model. The LH surge was blunted, but not blocked in these mice. In contrast, they showed reductions in FSH production, ovarian follicle development, and fertility. Addition of the Ctail altered the nature of agonist-induced calcium signaling required for normal FSH production. The loss of the GnRHR Ctail during mammalian evolution is unlikely to have conferred a selective advantage by enabling the LH surge. The adaptive significance of this specialization remains to be determined.
