Reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitis
Hepatic thyroid hormone signaling has an important role in the development and progression of nonalcoholic steatohepatitis (NASH). While the systemic levels of thyroid hormone might remain stable, there is evidence that the intracellular signaling machinery consisting of transporters, deiodinases an...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2018-12-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/7/12/EC-18-0499.xml |
| _version_ | 1818421002279845888 |
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| author | Christin Krause Martina Grohs Alexander T El Gammal Stefan Wolter Hendrik Lehnert Oliver Mann Jens Mittag Henriette Kirchner |
| author_facet | Christin Krause Martina Grohs Alexander T El Gammal Stefan Wolter Hendrik Lehnert Oliver Mann Jens Mittag Henriette Kirchner |
| author_sort | Christin Krause |
| collection | DOAJ |
| description | Hepatic thyroid hormone signaling has an important role in the development and progression of nonalcoholic steatohepatitis (NASH). While the systemic levels of thyroid hormone might remain stable, there is evidence that the intracellular signaling machinery consisting of transporters, deiodinases and receptors could be altered in NASH. However, clinical material from human liver biopsies of individuals with NASH has not been studied to date. In a cross-sectional study, we analyzed 85 liver biopsies from patients with different stages of NASH that underwent bariatric surgery. Using qPCR, we analyzed gene expression of thyroid hormone transporters NTCP (SLC10A1), MCT8 (SLC16A2) and OATP1C1 (SLCO1C1), thyroid hormone receptor α and β (THRA and THRB) and deiodinase type I, II and III (DIO1, DIO2, DIO3). The expression was correlated with serum TSH, triglyceride, HbA1c and NASH score and corrected for age or gender if required. While DIO2, DIO3 and SLCO1C1 were not expressed in human liver, we observed a significant negative correlation of THRB and DIO1 with age, and SLC16A2 with gender. THRB expression was also negatively associated with serum triglyceride levels and HbA1c. More importantly, its expression was inversely correlated with NASH score and further declined with age. Our data provide unique insight into the mRNA expression of thyroid hormone transporters, deiodinases and receptors in the human liver. The findings allow important conclusions on the intrahepatic mechanisms governing thyroid hormone action, indicating a possible tissue resistance to the circulating hormone in NASH, which becomes more prominent in advanced age. |
| first_indexed | 2024-12-14T13:03:26Z |
| format | Article |
| id | doaj.art-6a187e65294446b197f92f7400602be1 |
| institution | Directory Open Access Journal |
| issn | 2049-3614 2049-3614 |
| language | English |
| last_indexed | 2024-12-14T13:03:26Z |
| publishDate | 2018-12-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-6a187e65294446b197f92f7400602be12022-12-21T23:00:23ZengBioscientificaEndocrine Connections2049-36142049-36142018-12-0171214481456https://doi.org/10.1530/EC-18-0499Reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitisChristin Krause0Martina Grohs1Alexander T El Gammal2Stefan Wolter3Hendrik Lehnert4Oliver Mann5Jens Mittag6Henriette Kirchner7Epigenetics & Metabolism, Medical Department I, University of Lübeck, Lübeck, GermanyEpigenetics & Metabolism, Medical Department I, University of Lübeck, Lübeck, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMedical Department I, University of Lübeck, Lübeck, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyMolecular Endocrinology, Medical Department I, University of Lübeck, Lübeck, GermanyEpigenetics & Metabolism, Medical Department I, University of Lübeck, Lübeck, GermanyHepatic thyroid hormone signaling has an important role in the development and progression of nonalcoholic steatohepatitis (NASH). While the systemic levels of thyroid hormone might remain stable, there is evidence that the intracellular signaling machinery consisting of transporters, deiodinases and receptors could be altered in NASH. However, clinical material from human liver biopsies of individuals with NASH has not been studied to date. In a cross-sectional study, we analyzed 85 liver biopsies from patients with different stages of NASH that underwent bariatric surgery. Using qPCR, we analyzed gene expression of thyroid hormone transporters NTCP (SLC10A1), MCT8 (SLC16A2) and OATP1C1 (SLCO1C1), thyroid hormone receptor α and β (THRA and THRB) and deiodinase type I, II and III (DIO1, DIO2, DIO3). The expression was correlated with serum TSH, triglyceride, HbA1c and NASH score and corrected for age or gender if required. While DIO2, DIO3 and SLCO1C1 were not expressed in human liver, we observed a significant negative correlation of THRB and DIO1 with age, and SLC16A2 with gender. THRB expression was also negatively associated with serum triglyceride levels and HbA1c. More importantly, its expression was inversely correlated with NASH score and further declined with age. Our data provide unique insight into the mRNA expression of thyroid hormone transporters, deiodinases and receptors in the human liver. The findings allow important conclusions on the intrahepatic mechanisms governing thyroid hormone action, indicating a possible tissue resistance to the circulating hormone in NASH, which becomes more prominent in advanced age.https://ec.bioscientifica.com/view/journals/ec/7/12/EC-18-0499.xmlthyroid hormone receptorthyroid hormone transporterdeiodinaseliver |
| spellingShingle | Christin Krause Martina Grohs Alexander T El Gammal Stefan Wolter Hendrik Lehnert Oliver Mann Jens Mittag Henriette Kirchner Reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitis Endocrine Connections thyroid hormone receptor thyroid hormone transporter deiodinase liver |
| title | Reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitis |
| title_full | Reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitis |
| title_fullStr | Reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitis |
| title_full_unstemmed | Reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitis |
| title_short | Reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitis |
| title_sort | reduced expression of thyroid hormone receptor β in human nonalcoholic steatohepatitis |
| topic | thyroid hormone receptor thyroid hormone transporter deiodinase liver |
| url | https://ec.bioscientifica.com/view/journals/ec/7/12/EC-18-0499.xml |
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