ArticleMolecular endocrinology (Baltimore, Md.)2015
Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- ACTH and cortisol responses to CRH in acute, subacute, and prolonged critical illness: a randomized, double-blind, placebo-controlled, crossover cohort study.Intensive care medicine · 2018Trial
- Central Administration of Recombinant IGF1 Is Neuroprotective in a Rodent Model of Acute Liver Failure.International journal of molecular sciences · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Gut-Brain Axis and Bile Acid Signaling: Linking Microbial Metabolism to Brain Function and Metabolic Regulation.International journal of molecular sciences · 2025Review
- Adrenal High-Expressional CYP27A1 Mediates Bile Acid Increase and Functional Impairment in Adult Male Offspring by Prenatal Dexamethasone Exposure.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neuroprotection vs. Neurotoxicity: The Dual Impact of Brain Lipids in Depression.International journal of molecular sciences · 2025Review
- Role of Redox Homeostasis in the Communication Between Brain and Liver Through Extracellular Vesicles.Antioxidants (Basel, Switzerland) · 2024Review
- Gut-Brain Axis a Key Player to Control Gut Dysbiosis in Neurological Diseases.Molecular neurobiology · 2024Review
- Effects of cholestasis and hyperammonemia on dendritic spine density and turnover in rat hippocampal neurons.Scientific reports · 2024Article
- Emerging Roles of Bile Acids and TGR5 in the Central Nervous System: Molecular Functions and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Glucocorticoid receptor-dependent therapeutic efficacy of tauroursodeoxycholic acid in preclinical models of spinocerebellar ataxia type 3.The Journal of clinical investigation · 2024Article
- Grape Polyphenols May Prevent High-Fat Diet-Induced Dampening of the Hypothalamic-Pituitary-Adrenal Axis in Male Mice.Journal of the Endocrine Society · 2023Article
- An impaired pituitary-adrenal signalling axis in stable cirrhosis is linked to worse prognosis.JHEP reports : innovation in hepatology · 2023Article
- Roles of bile acids signaling in neuromodulation under physiological and pathological conditions.Cell & bioscience · 2023Review
- Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis.Frontiers in endocrinology · 2023Review
- The fibroblast growth factor system in cognitive disorders and dementia.Frontiers in neuroscience · 2023Review
- The Pathological Effects of Circulating Hydrophobic Bile Acids in Alzheimer's Disease.Journal of Alzheimer's disease reports · 2023Review
- GPCR-mediated effects of fatty acids and bile acids on glucose homeostasis.Frontiers in endocrinology · 2023Review
- Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling.International journal of molecular sciences · 2022Review
- Bile acids, bioactive signalling molecules in interoceptive gut-to-brain communication.The Journal of physiology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to occur during cholestatic liver injury. Furthermore, we have demonstrated that in a model of cholestasis, serum bile acids gain entry into the brain via a leaky blood brain barrier and that hypothalamic bile acid content is increased. Therefore, the aim of the current study was to determine the effects of bile acid signaling on the HPA axis. The data presented show that HPA axis suppression during cholestatic liver injury, specifically circulating corticosterone levels and hypothalamic corticotropin releasing hormone (CRH) expression, can be attenuated by administration of the bile acid sequestrant cholestyramine. Secondly, treatment of hypothalamic neurons with various bile acids suppressed CRH expression and secretion in vitro. However, in vivo HPA axis suppression was only evident after the central injection of the bile acids taurocholic acid or glycochenodeoxycholic acid but not the other bile acids studied. Furthermore, we demonstrate that taurocholic acid and glycochenodeoxycholic acid are exerting their effects on hypothalamic CRH expression after their uptake through the apical sodium-dependent bile acid transporter and subsequent activation of the glucocorticoid receptor. Taken together with previous studies, our data support the hypothesis that during cholestatic liver injury, bile acids gain entry into the brain, are transported into neurons through the apical sodium-dependent bile acid transporter and can activate the glucocorticoid receptor to suppress the HPA axis. These data also lend themselves to the broader hypothesis that bile acids may act as central modulators of hypothalamic peptides that may be altered during liver disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.