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Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin

The pineal gland is integral to the circadian timing system due to its role in nightly melatonin production. Retinoic acid (RA) is a potent regulator of gene transcription and has previously been found to exhibit diurnal changes in synthesis and signalling in the rat pineal gland. This study investi...

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Autores principales: Ashton, Anna, Clark, Jason, Fedo, Julia, Sementilli, Angelo, Fragoso, Yara D., McCaffery, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856906/
https://www.ncbi.nlm.nih.gov/pubmed/36672220
http://dx.doi.org/10.3390/cells12020286
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author Ashton, Anna
Clark, Jason
Fedo, Julia
Sementilli, Angelo
Fragoso, Yara D.
McCaffery, Peter
author_facet Ashton, Anna
Clark, Jason
Fedo, Julia
Sementilli, Angelo
Fragoso, Yara D.
McCaffery, Peter
author_sort Ashton, Anna
collection PubMed
description The pineal gland is integral to the circadian timing system due to its role in nightly melatonin production. Retinoic acid (RA) is a potent regulator of gene transcription and has previously been found to exhibit diurnal changes in synthesis and signalling in the rat pineal gland. This study investigated the potential for the interaction of these two systems. PCR was used to study gene expression in mouse and human pineal glands, ex-vivo organotypic cultured rat pineal gland and cell lines. The mouse and human pineal glands were both found to express the necessary components required for RA signalling. RA influences the circadian clock in the brain, therefore the short-term effect of RA on clock gene expression was determined in ex vivo rat pineal glands but was not found to rapidly regulate Per1, Per2, Bmal1, or Cry1. The interaction between RA and melatonin was also investigated and, unexpectedly, melatonin was found to suppress the induction of gene transcription by RA. This study demonstrates that pineal expression of the RA signalling system is conserved across mammalian species. There is no short-term regulation of the circadian clock but an inhibitory effect of melatonin on RA transcriptional activity was demonstrated, suggesting that there may be functional cross-talk between these systems.
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spelling pubmed-98569062023-01-21 Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin Ashton, Anna Clark, Jason Fedo, Julia Sementilli, Angelo Fragoso, Yara D. McCaffery, Peter Cells Article The pineal gland is integral to the circadian timing system due to its role in nightly melatonin production. Retinoic acid (RA) is a potent regulator of gene transcription and has previously been found to exhibit diurnal changes in synthesis and signalling in the rat pineal gland. This study investigated the potential for the interaction of these two systems. PCR was used to study gene expression in mouse and human pineal glands, ex-vivo organotypic cultured rat pineal gland and cell lines. The mouse and human pineal glands were both found to express the necessary components required for RA signalling. RA influences the circadian clock in the brain, therefore the short-term effect of RA on clock gene expression was determined in ex vivo rat pineal glands but was not found to rapidly regulate Per1, Per2, Bmal1, or Cry1. The interaction between RA and melatonin was also investigated and, unexpectedly, melatonin was found to suppress the induction of gene transcription by RA. This study demonstrates that pineal expression of the RA signalling system is conserved across mammalian species. There is no short-term regulation of the circadian clock but an inhibitory effect of melatonin on RA transcriptional activity was demonstrated, suggesting that there may be functional cross-talk between these systems. MDPI 2023-01-11 /pmc/articles/PMC9856906/ /pubmed/36672220 http://dx.doi.org/10.3390/cells12020286 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ashton, Anna
Clark, Jason
Fedo, Julia
Sementilli, Angelo
Fragoso, Yara D.
McCaffery, Peter
Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin
title Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin
title_full Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin
title_fullStr Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin
title_full_unstemmed Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin
title_short Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin
title_sort retinoic acid signalling in the pineal gland is conserved across mammalian species and its transcriptional activity is inhibited by melatonin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856906/
https://www.ncbi.nlm.nih.gov/pubmed/36672220
http://dx.doi.org/10.3390/cells12020286
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