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A synthetic kisspeptin analog that triggers ovulation and advances puberty
The neuropeptide kisspeptin and its receptor, KiSS1R, govern the reproductive timeline of mammals by triggering puberty onset and promoting ovulation by stimulating gonadotrophin-releasing hormone (GnRH) secretion. To overcome the drawback of kisspeptin short half-life we designed kisspeptin analogs...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887910/ https://www.ncbi.nlm.nih.gov/pubmed/27245315 http://dx.doi.org/10.1038/srep26908 |
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author | Decourt, C. Robert, V. Anger, K. Galibert, M. Madinier, J.-B. Liu, X. Dardente, H. Lomet, D. Delmas, A. F. Caraty, A. Herbison, A. E. Anderson, G. M Aucagne, V. Beltramo, M. |
author_facet | Decourt, C. Robert, V. Anger, K. Galibert, M. Madinier, J.-B. Liu, X. Dardente, H. Lomet, D. Delmas, A. F. Caraty, A. Herbison, A. E. Anderson, G. M Aucagne, V. Beltramo, M. |
author_sort | Decourt, C. |
collection | PubMed |
description | The neuropeptide kisspeptin and its receptor, KiSS1R, govern the reproductive timeline of mammals by triggering puberty onset and promoting ovulation by stimulating gonadotrophin-releasing hormone (GnRH) secretion. To overcome the drawback of kisspeptin short half-life we designed kisspeptin analogs combining original modifications, triazole peptidomimetic and albumin binding motif, to reduce proteolytic degradation and to slow down renal clearance, respectively. These analogs showed improved in vitro potency and dramatically enhanced pharmacodynamics. When injected intramuscularly into ewes (15 nmol/ewe) primed with a progestogen, the best analog (compound 6, C6) induced synchronized ovulations in both breeding and non-breeding seasons. Ovulations were fertile as demonstrated by the delivery of lambs at term. C6 was also fully active in both female and male mice but was completely inactive in KiSS1R KO mice. Electrophysiological recordings of GnRH neurons from brain slices of GnRH-GFP mice indicated that C6 exerted a direct excitatory action on GnRH neurons. Finally, in prepubertal female mice daily injections (0.3 nmol/mouse) for five days significantly advanced puberty. C6 ability to trigger ovulation and advance puberty demonstrates that kisspeptin analogs may find application in the management of livestock reproduction and opens new possibilities for the treatment of reproductive disorders in humans. |
format | Online Article Text |
id | pubmed-4887910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48879102016-06-09 A synthetic kisspeptin analog that triggers ovulation and advances puberty Decourt, C. Robert, V. Anger, K. Galibert, M. Madinier, J.-B. Liu, X. Dardente, H. Lomet, D. Delmas, A. F. Caraty, A. Herbison, A. E. Anderson, G. M Aucagne, V. Beltramo, M. Sci Rep Article The neuropeptide kisspeptin and its receptor, KiSS1R, govern the reproductive timeline of mammals by triggering puberty onset and promoting ovulation by stimulating gonadotrophin-releasing hormone (GnRH) secretion. To overcome the drawback of kisspeptin short half-life we designed kisspeptin analogs combining original modifications, triazole peptidomimetic and albumin binding motif, to reduce proteolytic degradation and to slow down renal clearance, respectively. These analogs showed improved in vitro potency and dramatically enhanced pharmacodynamics. When injected intramuscularly into ewes (15 nmol/ewe) primed with a progestogen, the best analog (compound 6, C6) induced synchronized ovulations in both breeding and non-breeding seasons. Ovulations were fertile as demonstrated by the delivery of lambs at term. C6 was also fully active in both female and male mice but was completely inactive in KiSS1R KO mice. Electrophysiological recordings of GnRH neurons from brain slices of GnRH-GFP mice indicated that C6 exerted a direct excitatory action on GnRH neurons. Finally, in prepubertal female mice daily injections (0.3 nmol/mouse) for five days significantly advanced puberty. C6 ability to trigger ovulation and advance puberty demonstrates that kisspeptin analogs may find application in the management of livestock reproduction and opens new possibilities for the treatment of reproductive disorders in humans. Nature Publishing Group 2016-06-01 /pmc/articles/PMC4887910/ /pubmed/27245315 http://dx.doi.org/10.1038/srep26908 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Decourt, C. Robert, V. Anger, K. Galibert, M. Madinier, J.-B. Liu, X. Dardente, H. Lomet, D. Delmas, A. F. Caraty, A. Herbison, A. E. Anderson, G. M Aucagne, V. Beltramo, M. A synthetic kisspeptin analog that triggers ovulation and advances puberty |
title | A synthetic kisspeptin analog that triggers ovulation and advances puberty |
title_full | A synthetic kisspeptin analog that triggers ovulation and advances puberty |
title_fullStr | A synthetic kisspeptin analog that triggers ovulation and advances puberty |
title_full_unstemmed | A synthetic kisspeptin analog that triggers ovulation and advances puberty |
title_short | A synthetic kisspeptin analog that triggers ovulation and advances puberty |
title_sort | synthetic kisspeptin analog that triggers ovulation and advances puberty |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887910/ https://www.ncbi.nlm.nih.gov/pubmed/27245315 http://dx.doi.org/10.1038/srep26908 |
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