Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver
Preclinical and clinical studies suggest that hypothyroidism might cause hepatic endocrine and metabolic disturbances with features that mimic deficiencies of testosterone and/or GH. The absence of physiological interactions between testosterone and GH can be linked to male differentiated liver dise...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1266150/full |
| _version_ | 1797400681504571392 |
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| author | Leandro Fernández-Pérez Leandro Fernández-Pérez Borja Guerra Borja Guerra Carlota Recio Juan José Cabrera-Galván Irma García Juan Vladimir De La Rosa Antonio Castrillo Antonio Castrillo Antonio Castrillo Diego Iglesias-Gato Mario Díaz |
| author_facet | Leandro Fernández-Pérez Leandro Fernández-Pérez Borja Guerra Borja Guerra Carlota Recio Juan José Cabrera-Galván Irma García Juan Vladimir De La Rosa Antonio Castrillo Antonio Castrillo Antonio Castrillo Diego Iglesias-Gato Mario Díaz |
| author_sort | Leandro Fernández-Pérez |
| collection | DOAJ |
| description | Preclinical and clinical studies suggest that hypothyroidism might cause hepatic endocrine and metabolic disturbances with features that mimic deficiencies of testosterone and/or GH. The absence of physiological interactions between testosterone and GH can be linked to male differentiated liver diseases. Testosterone plays relevant physiological effects on somatotropic-liver axis and liver composition and the liver is a primary organ of interactions between testosterone and GH. However, testosterone exerts many effects on liver through complex and poorly understood mechanisms. Testosterone impacts liver functions by binding to the Androgen Receptor, and, indirectly, through its conversion to estradiol, and cooperation with GH. However, the role of testosterone, and its interaction with GH, in the hypothyroid liver, remains unclear. In the present work, the effects of testosterone, and how they impact on GH-regulated whole transcriptome and lipid composition in the liver, were studied in the context of adult hypothyroid-orchiectomized rats. Testosterone replacement positively modulated somatotropic-liver axis and impacted liver transcriptome involved in lipid and glucose metabolism. In addition, testosterone enhanced the effects of GH on the transcriptome linked to lipid biosynthesis, oxidation-reduction, and metabolism of unsaturated and long-chain fatty acids (FA). However, testosterone decreased the hepatic content of cholesterol esters and triacylglycerols and increased fatty acids whereas GH increased neutral lipids and decreased polar lipids. Biological network analysis of the effects of testosterone on GH-regulated transcriptome confirmed a close connection with crucial proteins involved in steroid and fatty acid metabolism. Taken together, this comprehensive analysis of gene expression and lipid profiling in hypothyroid male liver reveals a functional interplay between testosterone and pulsed GH administration. |
| first_indexed | 2024-03-09T01:58:02Z |
| format | Article |
| id | doaj.art-be736f087692439fb358d1959e878247 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-09T01:58:02Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-be736f087692439fb358d1959e8782472023-12-08T11:43:01ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-12-011410.3389/fendo.2023.12661501266150Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liverLeandro Fernández-Pérez0Leandro Fernández-Pérez1Borja Guerra2Borja Guerra3Carlota Recio4Juan José Cabrera-Galván5Irma García6Juan Vladimir De La Rosa7Antonio Castrillo8Antonio Castrillo9Antonio Castrillo10Diego Iglesias-Gato11Mario Díaz12Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Farmacología Molecular y Traslacional, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, SpainUnidad de Biomedicina del Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS) Asociada al Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid, Las Palmas de Gran Canaria, SpainInstituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Farmacología Molecular y Traslacional, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, SpainUnidad de Biomedicina del Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS) Asociada al Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid, Las Palmas de Gran Canaria, SpainInstituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Farmacología Molecular y Traslacional, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, SpainInstituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Farmacología Molecular y Traslacional, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, SpainDepartmento de Física Básica, Grupo de Fisiología y Biofísica de Membranas, Universidad de La Laguna, La Laguna, SpainInstituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Farmacología Molecular y Traslacional, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, SpainInstituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Farmacología Molecular y Traslacional, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, SpainUnidad de Biomedicina del Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS) Asociada al Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid, Las Palmas de Gran Canaria, SpainInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC), Centro Mixto CSIC-Universidad Autónoma de Madrid, Madrid, SpainNovo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartmento de Física Básica, Grupo de Fisiología y Biofísica de Membranas, Universidad de La Laguna, La Laguna, SpainPreclinical and clinical studies suggest that hypothyroidism might cause hepatic endocrine and metabolic disturbances with features that mimic deficiencies of testosterone and/or GH. The absence of physiological interactions between testosterone and GH can be linked to male differentiated liver diseases. Testosterone plays relevant physiological effects on somatotropic-liver axis and liver composition and the liver is a primary organ of interactions between testosterone and GH. However, testosterone exerts many effects on liver through complex and poorly understood mechanisms. Testosterone impacts liver functions by binding to the Androgen Receptor, and, indirectly, through its conversion to estradiol, and cooperation with GH. However, the role of testosterone, and its interaction with GH, in the hypothyroid liver, remains unclear. In the present work, the effects of testosterone, and how they impact on GH-regulated whole transcriptome and lipid composition in the liver, were studied in the context of adult hypothyroid-orchiectomized rats. Testosterone replacement positively modulated somatotropic-liver axis and impacted liver transcriptome involved in lipid and glucose metabolism. In addition, testosterone enhanced the effects of GH on the transcriptome linked to lipid biosynthesis, oxidation-reduction, and metabolism of unsaturated and long-chain fatty acids (FA). However, testosterone decreased the hepatic content of cholesterol esters and triacylglycerols and increased fatty acids whereas GH increased neutral lipids and decreased polar lipids. Biological network analysis of the effects of testosterone on GH-regulated transcriptome confirmed a close connection with crucial proteins involved in steroid and fatty acid metabolism. Taken together, this comprehensive analysis of gene expression and lipid profiling in hypothyroid male liver reveals a functional interplay between testosterone and pulsed GH administration.https://www.frontiersin.org/articles/10.3389/fendo.2023.1266150/fullhypothyroidismtestosteroneGHlivertranscriptomelipids |
| spellingShingle | Leandro Fernández-Pérez Leandro Fernández-Pérez Borja Guerra Borja Guerra Carlota Recio Juan José Cabrera-Galván Irma García Juan Vladimir De La Rosa Antonio Castrillo Antonio Castrillo Antonio Castrillo Diego Iglesias-Gato Mario Díaz Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver Frontiers in Endocrinology hypothyroidism testosterone GH liver transcriptome lipids |
| title | Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver |
| title_full | Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver |
| title_fullStr | Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver |
| title_full_unstemmed | Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver |
| title_short | Transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver |
| title_sort | transcriptomic and lipid profiling analysis reveals a functional interplay between testosterone and growth hormone in hypothyroid liver |
| topic | hypothyroidism testosterone GH liver transcriptome lipids |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1266150/full |
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