ArticleLiver international : official journal of the International Association for the Study of the Liver2019
Bile acids increase steroidogenesis in cholemic mice and induce cortisol secretion in adrenocortical H295R cells via S1PR2, ERK and SF-1.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
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- Plasma Lipidomics Reveals Lipid Signatures of Early Pregnancy in Mares.International journal of molecular sciences · 2024Article
- Pubertal Girls With Overweight/Obesity Have Higher Androgen Levels-Can Metabolomics Tell us Why?The Journal of clinical endocrinology and metabolism · 2024Article
- Experimental hepatic encephalopathy causes early but sustained glial transcriptional changes.Journal of neuroinflammation · 2023Article
- Enterohepatic and non-canonical roles of farnesoid X receptor in controlling lipid and glucose metabolism.Molecular and cellular endocrinology · 2022Review
- High-Amylose Corn Starch Regulated Gut Microbiota and Serum Bile Acids in High-Fat Diet-Induced Obese Mice.International journal of molecular sciences · 2022Article
- The Role of Bile Acids in the Human Body and in the Development of Diseases.Molecules (Basel, Switzerland) · 2022Review
- Hypercortisolism in patients with cholestasis is associated with disease severity.BMC gastroenterology · 2021Article
- Corrigendum.Liver international : official journal of the International Association for the Study of the Liver · 2021Article
- Bile acids increase steroidogenesis in cholemic mice and induce cortisol secretion in adrenocortical H295R cells via S1PR2, ERK and SF-1.Liver international : official journal of the International Association for the Study of the Liver · 2019Article
Corrections and comments
- Erratum issuedCorrigendum.2021
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
aimsBile acids are now accepted as central signalling molecules for the regulation of glucose, amino acid and lipid metabolism. Adrenal gland cortex cells express the bile acid receptors farnesoid X receptor (FXR), the G protein-coupled bile acid receptor (TGR5) and the sphingosine-1-phosphate receptor 2 (S1PR2). We aimed to determine the effects of cholestasis and more specifically of bile acids on cortisol production.
methodsFXR and TGR5 knockout mice and controls were subjected to common bile duct ligation (CBDL) or chenodeoxycholic acid (CDCA) feeding to model cholestasis. Human adrenocortical H295R cells were challenged with bile acids for mechanistic studies.
resultsWe found that CBDL and CDCA feeding increased the levels of corticosterone, the rodent equivalent to human cortisol and mRNA and protein levels of steroidogenesis-related enzymes in adrenals independent of FXR and TGR5. Taurine-conjugated CDCA (TCDCA) significantly stimulated cortisol secretion, phosphorylation of extracellular signal-regulated kinase (ERK) and expression of steroidogenesis-related genes in human adrenocortical H295R cells. FXR and TGR5 agonists failed to induce cortisol secretion in H295R cells. S1PR2 inhibition significantly abolished TCDCA-induced cortisol secretion, lowered phosphorylation of ERK and abrogated enhanced transcription of steroidogenesis-related genes in H295R cells. Likewise, siRNA S1PR2 treatment reduced the phosphorylation of ERK and cortisol secretion. Steroidogenic factor-1 (SF-1) transactivation activity was increased upon TCDCA treatment suggesting that bile acid signalling is linked to SF-1. Treatment with SF-1 inverse agonist AC45594 also reduced TCDCA-induced steroidogenesis.
conclusionsOur findings indicate that supraphysiological bile acid levels as observed in cholestasis stimulate steroidogenesis via an S1PR2-ERK-SF-1 signalling pathway.
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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.