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Relationship between serum thyroid hormones and their associated metabolites, and gene expression bioindicators in the back skin of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis
Anuran metamorphosis is characterized by profound morphological changes including remodeling of tissues and organs. This transition is initiated by thyroid hormones (THs). However, the current knowledge of changing levels of THs during metamorphosis relies on pooled samples using methods known for h...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889540/ https://www.ncbi.nlm.nih.gov/pubmed/36743912 http://dx.doi.org/10.3389/fendo.2022.1103051 |
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author | Poulsen, Rikke Jackman, Shireen H. Hansen, Martin Helbing, Caren C. |
author_facet | Poulsen, Rikke Jackman, Shireen H. Hansen, Martin Helbing, Caren C. |
author_sort | Poulsen, Rikke |
collection | PubMed |
description | Anuran metamorphosis is characterized by profound morphological changes including remodeling of tissues and organs. This transition is initiated by thyroid hormones (THs). However, the current knowledge of changing levels of THs during metamorphosis relies on pooled samples using methods known for high variability with sparse reporting of measured variation. Moreover, establishing a clear linkage between key gene expression bioindicators and TH levels throughout the metamorphic process is needed. Using state-of-the-art ultra-high performance liquid chromatography isotope-dilution tandem mass spectrometry, we targeted 12 THs and metabolites in the serum of Rana [Lithobates] catesbeiana (n=5-10) across seven distinct postembryonic stages beginning with premetamorphic tadpoles (Gosner stage 31-33) and continuing through metamorphosis to a juvenile frog (Gosner stage 46). TH levels were related to TH-relevant gene transcripts (thra, thrb, and thibz) in back skin of the same individual animals. Significant increases from basal levels were observed for thyroxine (T4) and 3,3’,5-triiodothyronine (T3) at Gosner stage 41, reaching maximal levels at Gosner stage 44 (28 ± 10 and 2.3 ± 0.5 ng/mL, respectively), and decreasing to basal levels in juvenile frogs. In contrast, 3,5-diiodothyronine (T2) increased significantly at Gosner stage 40 and was maintained elevated until stage 44. While thra transcript levels remained constant and then decreased at the end of metamorphic climax, thrb and thibz were induced to maximal levels at Gosner stage 41, followed by a decrease to basal levels in the froglet. This exemplifies the exquisite timing of events during metamorphosis as classic early response genes are transcribed in anticipation of peak TH concentrations. The distinct T2 concentration profile suggests a biological role of this biomolecule in anuran postembryonic development and an additional aspect that may be a target of anthropogenic chemicals that can disrupt anuran metamorphosis and TH signalling. Hence, as a second aim of the study, we set out to find additional bioindicators of metamorphosis, which can aid future investigations of developmental disruption. Using a sensitive nanoLC-Orbitrap system an untargeted analysis workflow was applied. Among 6,062 endogenous metabolites, 421 showed metamorphosis-dependent concentration dynamics. These potential bioindicators included several carnitines, prostaglandins and some steroid hormones. |
format | Online Article Text |
id | pubmed-9889540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98895402023-02-02 Relationship between serum thyroid hormones and their associated metabolites, and gene expression bioindicators in the back skin of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis Poulsen, Rikke Jackman, Shireen H. Hansen, Martin Helbing, Caren C. Front Endocrinol (Lausanne) Endocrinology Anuran metamorphosis is characterized by profound morphological changes including remodeling of tissues and organs. This transition is initiated by thyroid hormones (THs). However, the current knowledge of changing levels of THs during metamorphosis relies on pooled samples using methods known for high variability with sparse reporting of measured variation. Moreover, establishing a clear linkage between key gene expression bioindicators and TH levels throughout the metamorphic process is needed. Using state-of-the-art ultra-high performance liquid chromatography isotope-dilution tandem mass spectrometry, we targeted 12 THs and metabolites in the serum of Rana [Lithobates] catesbeiana (n=5-10) across seven distinct postembryonic stages beginning with premetamorphic tadpoles (Gosner stage 31-33) and continuing through metamorphosis to a juvenile frog (Gosner stage 46). TH levels were related to TH-relevant gene transcripts (thra, thrb, and thibz) in back skin of the same individual animals. Significant increases from basal levels were observed for thyroxine (T4) and 3,3’,5-triiodothyronine (T3) at Gosner stage 41, reaching maximal levels at Gosner stage 44 (28 ± 10 and 2.3 ± 0.5 ng/mL, respectively), and decreasing to basal levels in juvenile frogs. In contrast, 3,5-diiodothyronine (T2) increased significantly at Gosner stage 40 and was maintained elevated until stage 44. While thra transcript levels remained constant and then decreased at the end of metamorphic climax, thrb and thibz were induced to maximal levels at Gosner stage 41, followed by a decrease to basal levels in the froglet. This exemplifies the exquisite timing of events during metamorphosis as classic early response genes are transcribed in anticipation of peak TH concentrations. The distinct T2 concentration profile suggests a biological role of this biomolecule in anuran postembryonic development and an additional aspect that may be a target of anthropogenic chemicals that can disrupt anuran metamorphosis and TH signalling. Hence, as a second aim of the study, we set out to find additional bioindicators of metamorphosis, which can aid future investigations of developmental disruption. Using a sensitive nanoLC-Orbitrap system an untargeted analysis workflow was applied. Among 6,062 endogenous metabolites, 421 showed metamorphosis-dependent concentration dynamics. These potential bioindicators included several carnitines, prostaglandins and some steroid hormones. Frontiers Media S.A. 2023-01-18 /pmc/articles/PMC9889540/ /pubmed/36743912 http://dx.doi.org/10.3389/fendo.2022.1103051 Text en Copyright © 2023 Poulsen, Jackman, Hansen and Helbing https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Poulsen, Rikke Jackman, Shireen H. Hansen, Martin Helbing, Caren C. Relationship between serum thyroid hormones and their associated metabolites, and gene expression bioindicators in the back skin of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis |
title | Relationship between serum thyroid hormones and their associated metabolites, and gene expression bioindicators in the back skin of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis |
title_full | Relationship between serum thyroid hormones and their associated metabolites, and gene expression bioindicators in the back skin of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis |
title_fullStr | Relationship between serum thyroid hormones and their associated metabolites, and gene expression bioindicators in the back skin of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis |
title_full_unstemmed | Relationship between serum thyroid hormones and their associated metabolites, and gene expression bioindicators in the back skin of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis |
title_short | Relationship between serum thyroid hormones and their associated metabolites, and gene expression bioindicators in the back skin of Rana [Lithobates] catesbeiana tadpoles and frogs during metamorphosis |
title_sort | relationship between serum thyroid hormones and their associated metabolites, and gene expression bioindicators in the back skin of rana [lithobates] catesbeiana tadpoles and frogs during metamorphosis |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889540/ https://www.ncbi.nlm.nih.gov/pubmed/36743912 http://dx.doi.org/10.3389/fendo.2022.1103051 |
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