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The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors
Melatonin is a known modulator of follicle development; it acts through several molecular cascades via binding to its two specific receptors MT1 and MT2. Even though it is believed that melatonin can modulate granulosa cell (GC) functions, there is still limited knowledge of how it can act in human...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584952/ https://www.ncbi.nlm.nih.gov/pubmed/36266374 http://dx.doi.org/10.1038/s41598-022-21162-y |
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author | Arjoune, Asma Sirard, Marc-André |
author_facet | Arjoune, Asma Sirard, Marc-André |
author_sort | Arjoune, Asma |
collection | PubMed |
description | Melatonin is a known modulator of follicle development; it acts through several molecular cascades via binding to its two specific receptors MT1 and MT2. Even though it is believed that melatonin can modulate granulosa cell (GC) functions, there is still limited knowledge of how it can act in human GC through MT1 and MT2 and which one is more implicated in the effects of melatonin on the metabolic processes in the dominant follicle. To better characterize the roles of these receptors on the effects of melatonin on follicular development, human granulosa-like tumor cells (KGN) were treated with specific melatonin receptor agonists and antagonists, and gene expression was analyzed with RNA-seq technology. Following appropriate normalization and the application of a fold change cut-off of 1.5 (FC 1.5, p ≤ 0.05) for each treatment, lists of the principal differentially expressed genes (DEGs) are generated. Analysis of major upstream regulators suggested that the MT1 receptor may be involved in the melatonin antiproliferative effect by reprogramming the metabolism of human GC by activating the PKB signaling pathway. Our data suggest that melatonin may act complementary through both MT1 and MT2 receptors to modulate human GC steroidogenesis, proliferation, and differentiation. However, MT2 receptors may be the ones implicated in transducing the effects of melatonin on the prevention of GC luteinization and follicle atresia at the antral follicular stage through stimulating the PKA pathway. |
format | Online Article Text |
id | pubmed-9584952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95849522022-10-22 The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors Arjoune, Asma Sirard, Marc-André Sci Rep Article Melatonin is a known modulator of follicle development; it acts through several molecular cascades via binding to its two specific receptors MT1 and MT2. Even though it is believed that melatonin can modulate granulosa cell (GC) functions, there is still limited knowledge of how it can act in human GC through MT1 and MT2 and which one is more implicated in the effects of melatonin on the metabolic processes in the dominant follicle. To better characterize the roles of these receptors on the effects of melatonin on follicular development, human granulosa-like tumor cells (KGN) were treated with specific melatonin receptor agonists and antagonists, and gene expression was analyzed with RNA-seq technology. Following appropriate normalization and the application of a fold change cut-off of 1.5 (FC 1.5, p ≤ 0.05) for each treatment, lists of the principal differentially expressed genes (DEGs) are generated. Analysis of major upstream regulators suggested that the MT1 receptor may be involved in the melatonin antiproliferative effect by reprogramming the metabolism of human GC by activating the PKB signaling pathway. Our data suggest that melatonin may act complementary through both MT1 and MT2 receptors to modulate human GC steroidogenesis, proliferation, and differentiation. However, MT2 receptors may be the ones implicated in transducing the effects of melatonin on the prevention of GC luteinization and follicle atresia at the antral follicular stage through stimulating the PKA pathway. Nature Publishing Group UK 2022-10-20 /pmc/articles/PMC9584952/ /pubmed/36266374 http://dx.doi.org/10.1038/s41598-022-21162-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Arjoune, Asma Sirard, Marc-André The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors |
title | The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors |
title_full | The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors |
title_fullStr | The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors |
title_full_unstemmed | The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors |
title_short | The genomic response of human granulosa cells (KGN) to melatonin and specific agonists/antagonists to the melatonin receptors |
title_sort | genomic response of human granulosa cells (kgn) to melatonin and specific agonists/antagonists to the melatonin receptors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584952/ https://www.ncbi.nlm.nih.gov/pubmed/36266374 http://dx.doi.org/10.1038/s41598-022-21162-y |
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