Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia
BackgroundHyperuricemia is a known risk factor of lipid metabolism disorder. However, the mechanisms have not been fully understood.MethodsThe serum samples from hyperuricemia subjects were used to analyze the correlation between serum uric acid and clinical characteristics. Hyperuricemia mice induc...
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1279205/full |
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| author | Ruixia Bao Beibei Chen Jujie Pan Alexander Wang Haiyang Yu Qian Chen Yi Zhang Tao Wang Tao Wang |
| author_facet | Ruixia Bao Beibei Chen Jujie Pan Alexander Wang Haiyang Yu Qian Chen Yi Zhang Tao Wang Tao Wang |
| author_sort | Ruixia Bao |
| collection | DOAJ |
| description | BackgroundHyperuricemia is a known risk factor of lipid metabolism disorder. However, the mechanisms have not been fully understood.MethodsThe serum samples from hyperuricemia subjects were used to analyze the correlation between serum uric acid and clinical characteristics. Hyperuricemia mice induced by potassium oxonate (PO) and adenine were used to explore glucocorticoid metabolism.ResultsIn hyperuricemia patients, the levels of serum uric acid were positively correlated with the levels of γ-glutamyltransferase, associated with a cortisol metabolism disorder. In hyperuricemia state, the adrenal glands failed to respond to adrenocorticotropic hormone properly, leading to low cortisol, but not corticosterone production, and decreased mRNA levels of aldosterone synthase, 11β-hydroxylase, and 3β-hydroxysteroid dehydrogenase 1, three key enzymes for cortisol synthesis. The expression of both hepatic 5α-reductase and renal 11β-hydroxysteroid dehydrogenase 2 was significantly reduced, which led to low cortisol clearance. We denominated this cortisol metabolism disorder in hyperuricemia as pseudohypoadrenalism (PHAL).ConclusionPHAL increased exposure to the bioavailable cortisol in the liver, leading to local amplification of the biological action of corticosteroids. Unregulated biosynthesis pathway of bile acid expanded bile acid pool, and further aggravated cholestatic liver injury. |
| first_indexed | 2024-03-11T10:12:34Z |
| format | Article |
| id | doaj.art-3149743c06da44be826e0a4e1d161cad |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-11T10:12:34Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-3149743c06da44be826e0a4e1d161cad2023-11-16T13:15:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-11-011410.3389/fendo.2023.12792051279205Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemiaRuixia Bao0Beibei Chen1Jujie Pan2Alexander Wang3Haiyang Yu4Qian Chen5Yi Zhang6Tao Wang7Tao Wang8State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, ChinaCollege of Education, University of Texas at Austin, Austin, TX, United StatesState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, ChinaState Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackgroundHyperuricemia is a known risk factor of lipid metabolism disorder. However, the mechanisms have not been fully understood.MethodsThe serum samples from hyperuricemia subjects were used to analyze the correlation between serum uric acid and clinical characteristics. Hyperuricemia mice induced by potassium oxonate (PO) and adenine were used to explore glucocorticoid metabolism.ResultsIn hyperuricemia patients, the levels of serum uric acid were positively correlated with the levels of γ-glutamyltransferase, associated with a cortisol metabolism disorder. In hyperuricemia state, the adrenal glands failed to respond to adrenocorticotropic hormone properly, leading to low cortisol, but not corticosterone production, and decreased mRNA levels of aldosterone synthase, 11β-hydroxylase, and 3β-hydroxysteroid dehydrogenase 1, three key enzymes for cortisol synthesis. The expression of both hepatic 5α-reductase and renal 11β-hydroxysteroid dehydrogenase 2 was significantly reduced, which led to low cortisol clearance. We denominated this cortisol metabolism disorder in hyperuricemia as pseudohypoadrenalism (PHAL).ConclusionPHAL increased exposure to the bioavailable cortisol in the liver, leading to local amplification of the biological action of corticosteroids. Unregulated biosynthesis pathway of bile acid expanded bile acid pool, and further aggravated cholestatic liver injury.https://www.frontiersin.org/articles/10.3389/fendo.2023.1279205/fullhyperuricemialiver injurylipid metabolism disordercortisolpseudohypoadrenalism |
| spellingShingle | Ruixia Bao Beibei Chen Jujie Pan Alexander Wang Haiyang Yu Qian Chen Yi Zhang Tao Wang Tao Wang Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia Frontiers in Endocrinology hyperuricemia liver injury lipid metabolism disorder cortisol pseudohypoadrenalism |
| title | Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia |
| title_full | Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia |
| title_fullStr | Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia |
| title_full_unstemmed | Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia |
| title_short | Pseudohypoadrenalism, a subclinical cortisol metabolism disorder in hyperuricemia |
| title_sort | pseudohypoadrenalism a subclinical cortisol metabolism disorder in hyperuricemia |
| topic | hyperuricemia liver injury lipid metabolism disorder cortisol pseudohypoadrenalism |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1279205/full |
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