Addition of a carboxy terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice
- McGill University, Canada
- Universite de Montreal, Canada
- Universidad Nacional Autónoma de México, Mexico
- Leiden University Medical Center, Netherlands
- The University of Queensland, Australia
- Imperial College London, United Kingdom
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Yorgui Santiago-Andres
Aylin C Hanyaloglu
Tatiana Fiordelisio
Funding
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Rajan Dighe, Indian Institute of Science Bangalore, India
Ethics
Animal experimentation: All mouse experiments in Canada were performed in accordance with institutional and federal guidelines and were approved by the McGill University Facility Animal Care Committee (DOW-A; protocol 5204). Mouse studies conducted at the National University of Mexico were performed under an institutional protocol similar to the United States Public Health Service Guide for the Care and Use of Laboratory Animals, and according to the Official Mexican Guide from the Secretary of Agriculture (SAGARPA NOM-062-Z00-1999).
Version history
- Received: August 10, 2021
- Preprint posted: September 16, 2021 (view preprint)
- Accepted: December 6, 2021
- Accepted Manuscript published: December 23, 2021 (version 1)
- Version of Record published: January 7, 2022 (version 2)
Copyright
© 2021, Toufaily et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Addition of a carboxy terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice
eLife 10:e72937.
https://doi.org/10.7554/eLife.72937
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