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Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice
Infertility associated with obesity is characterized by abnormal hormone release from reproductive tissues in the hypothalamus, pituitary, and ovary. These tissues maintain insulin sensitivity upon peripheral insulin resistance. Insulin receptor signaling may play a role in the dysregulation of gona...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363364/ https://www.ncbi.nlm.nih.gov/pubmed/25780937 http://dx.doi.org/10.1371/journal.pone.0119995 |
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author | DiVall, Sara A. Herrera, Danny Sklar, Bonnie Wu, Sheng Wondisford, Fredric Radovick, Sally Wolfe, Andrew |
author_facet | DiVall, Sara A. Herrera, Danny Sklar, Bonnie Wu, Sheng Wondisford, Fredric Radovick, Sally Wolfe, Andrew |
author_sort | DiVall, Sara A. |
collection | PubMed |
description | Infertility associated with obesity is characterized by abnormal hormone release from reproductive tissues in the hypothalamus, pituitary, and ovary. These tissues maintain insulin sensitivity upon peripheral insulin resistance. Insulin receptor signaling may play a role in the dysregulation of gonadotropin-releasing hormone (GnRH) secretion in obesity, but the interdependence of hormone secretion in the reproductive axis and the multi-hormone and tissue dysfunction in obesity hinders investigations of putative contributing factors to the disrupted GnRH secretion. To determine the role of GnRH insulin receptor signaling in the dysregulation of GnRH secretion in obesity, we created murine models of diet-induced obesity (DIO) with and without intact insulin signaling in the GnRH neuron. Obese control female mice were infertile with higher luteinizing hormone levels and higher GnRH pulse amplitude and total pulsatile secretion compared to lean control mice. In contrast, DIO mice with a GnRH specific knockout of insulin receptor had improved fertility, luteinizing hormone levels approaching lean mice, and GnRH pulse amplitude and total secretion similar to lean mice. Pituitary responsiveness was similar between genotypes. These results suggest that in the obese state, insulin receptor signaling in GnRH neurons increases GnRH pulsatile secretion and consequent LH secretion, contributing to reproductive dysfunction. |
format | Online Article Text |
id | pubmed-4363364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43633642015-03-23 Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice DiVall, Sara A. Herrera, Danny Sklar, Bonnie Wu, Sheng Wondisford, Fredric Radovick, Sally Wolfe, Andrew PLoS One Research Article Infertility associated with obesity is characterized by abnormal hormone release from reproductive tissues in the hypothalamus, pituitary, and ovary. These tissues maintain insulin sensitivity upon peripheral insulin resistance. Insulin receptor signaling may play a role in the dysregulation of gonadotropin-releasing hormone (GnRH) secretion in obesity, but the interdependence of hormone secretion in the reproductive axis and the multi-hormone and tissue dysfunction in obesity hinders investigations of putative contributing factors to the disrupted GnRH secretion. To determine the role of GnRH insulin receptor signaling in the dysregulation of GnRH secretion in obesity, we created murine models of diet-induced obesity (DIO) with and without intact insulin signaling in the GnRH neuron. Obese control female mice were infertile with higher luteinizing hormone levels and higher GnRH pulse amplitude and total pulsatile secretion compared to lean control mice. In contrast, DIO mice with a GnRH specific knockout of insulin receptor had improved fertility, luteinizing hormone levels approaching lean mice, and GnRH pulse amplitude and total secretion similar to lean mice. Pituitary responsiveness was similar between genotypes. These results suggest that in the obese state, insulin receptor signaling in GnRH neurons increases GnRH pulsatile secretion and consequent LH secretion, contributing to reproductive dysfunction. Public Library of Science 2015-03-17 /pmc/articles/PMC4363364/ /pubmed/25780937 http://dx.doi.org/10.1371/journal.pone.0119995 Text en © 2015 DiVall 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article DiVall, Sara A. Herrera, Danny Sklar, Bonnie Wu, Sheng Wondisford, Fredric Radovick, Sally Wolfe, Andrew Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice |
title | Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice |
title_full | Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice |
title_fullStr | Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice |
title_full_unstemmed | Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice |
title_short | Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice |
title_sort | insulin receptor signaling in the gnrh neuron plays a role in the abnormal gnrh pulsatility of obese female mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363364/ https://www.ncbi.nlm.nih.gov/pubmed/25780937 http://dx.doi.org/10.1371/journal.pone.0119995 |
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