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In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation
Kisspeptins (KPs) and their receptor (GPR54 or KiSS1R) play a key-role in regulation of the hypothalamic-pituitary-gonadal axis and are therefore interesting targets for therapeutic interventions in the field of reproductive endocrinology. As dogs show a rapid and robust LH response after the admini...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484485/ https://www.ncbi.nlm.nih.gov/pubmed/28650956 http://dx.doi.org/10.1371/journal.pone.0179156 |
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author | Albers-Wolthers, C. H. J. de Gier, J. Walen, M. van Kooten, P. J. S. Lambalk, C. B. Leegwater, P. A. J. Roelen, B. A. J. Schaefers-Okkens, A. C. Rutten, V. P. M. G. Millar, R. P. M. Kooistra, H. S. |
author_facet | Albers-Wolthers, C. H. J. de Gier, J. Walen, M. van Kooten, P. J. S. Lambalk, C. B. Leegwater, P. A. J. Roelen, B. A. J. Schaefers-Okkens, A. C. Rutten, V. P. M. G. Millar, R. P. M. Kooistra, H. S. |
author_sort | Albers-Wolthers, C. H. J. |
collection | PubMed |
description | Kisspeptins (KPs) and their receptor (GPR54 or KiSS1R) play a key-role in regulation of the hypothalamic-pituitary-gonadal axis and are therefore interesting targets for therapeutic interventions in the field of reproductive endocrinology. As dogs show a rapid and robust LH response after the administration of KP10, they can serve as a good animal model for research concerning KP signaling. The aims of the present study were to test the antagonistic properties of KP analogs p234, p271, p354, and p356 in vitro, by determining the intracellular Ca(2+) response of CHEM1 cells that stably express human GPR54, and to study the in vivo effects of these peptides on basal plasma LH concentration and the KP10-induced LH response in female dogs. Exposure of the CHEM1 cells to KP-10 resulted in a clear Ca(2+) response. P234, p271, p354, and p356 did not prevent or lower the KP10-induced Ca(2+) response. Moreover, the in vivo studies in the dogs showed that none of these supposed antagonists lowered the basal plasma LH concentration and none of the peptides lowered the KP10-induced LH response. In conclusion, p234, p271, p354, and p356 had no antagonistic effects in vitro nor any effect on basal and kisspeptin-stimulated plasma LH concentration in female dogs. |
format | Online Article Text |
id | pubmed-5484485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54844852017-07-11 In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation Albers-Wolthers, C. H. J. de Gier, J. Walen, M. van Kooten, P. J. S. Lambalk, C. B. Leegwater, P. A. J. Roelen, B. A. J. Schaefers-Okkens, A. C. Rutten, V. P. M. G. Millar, R. P. M. Kooistra, H. S. PLoS One Research Article Kisspeptins (KPs) and their receptor (GPR54 or KiSS1R) play a key-role in regulation of the hypothalamic-pituitary-gonadal axis and are therefore interesting targets for therapeutic interventions in the field of reproductive endocrinology. As dogs show a rapid and robust LH response after the administration of KP10, they can serve as a good animal model for research concerning KP signaling. The aims of the present study were to test the antagonistic properties of KP analogs p234, p271, p354, and p356 in vitro, by determining the intracellular Ca(2+) response of CHEM1 cells that stably express human GPR54, and to study the in vivo effects of these peptides on basal plasma LH concentration and the KP10-induced LH response in female dogs. Exposure of the CHEM1 cells to KP-10 resulted in a clear Ca(2+) response. P234, p271, p354, and p356 did not prevent or lower the KP10-induced Ca(2+) response. Moreover, the in vivo studies in the dogs showed that none of these supposed antagonists lowered the basal plasma LH concentration and none of the peptides lowered the KP10-induced LH response. In conclusion, p234, p271, p354, and p356 had no antagonistic effects in vitro nor any effect on basal and kisspeptin-stimulated plasma LH concentration in female dogs. Public Library of Science 2017-06-26 /pmc/articles/PMC5484485/ /pubmed/28650956 http://dx.doi.org/10.1371/journal.pone.0179156 Text en © 2017 Albers-Wolthers et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Albers-Wolthers, C. H. J. de Gier, J. Walen, M. van Kooten, P. J. S. Lambalk, C. B. Leegwater, P. A. J. Roelen, B. A. J. Schaefers-Okkens, A. C. Rutten, V. P. M. G. Millar, R. P. M. Kooistra, H. S. In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation |
title | In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation |
title_full | In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation |
title_fullStr | In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation |
title_full_unstemmed | In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation |
title_short | In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation |
title_sort | in vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on gpr54 activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484485/ https://www.ncbi.nlm.nih.gov/pubmed/28650956 http://dx.doi.org/10.1371/journal.pone.0179156 |
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