Epistane, an anabolic steroid used for recreational purposes, causes cholestasis with elevated levels of cholic acid conjugates, by upregulating bile acid synthesis (CYP8B1) and cross-talking with nuclear receptors in human hepatocytes

2020 ◽  
Vol 94 (2) ◽  
pp. 589-607 ◽  
Author(s):  
Petar D. Petrov ◽  
Leonor Fernández-Murga ◽  
Isabel Conde ◽  
Teresa Martínez-Sena ◽  
Carla Guzmán ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Nuclear Receptors ◽  
Anabolic Steroid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Human Hepatocytes

scholarly journals Bile acid synthesis in cultured human hepatocytes: support for an alternative biosynthetic pathway to cholic acid

Hepatology ◽  
2000 ◽  
Vol 31 (6) ◽  
pp. 1305-1312 ◽  
Author(s):  
Magnus Axelson ◽  
Ewa Ellis ◽  
Birgitta Mörk ◽  
Kristina Garmark ◽  
Anna Abrahamsson ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Biosynthetic Pathway ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Human Hepatocytes

scholarly journals Cholic acid for primary bile acid synthesis defects: a life-saving therapy allowing a favorable outcome in adulthood

2018 ◽  
Vol 13 (1) ◽  
Author(s):  
Emmanuel Gonzales ◽  
Lorenza Matarazzo ◽  
Stéphanie Franchi-Abella ◽  
Alain Dabadie ◽  
Joseph Cohen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Favorable Outcome ◽  
Life Saving ◽  
Primary Bile Acid

scholarly journals Atypical clinical presentation and successful treatment with oral cholic acid of a child with defective bile acid synthesis due to a novel mutation in the HSD3B7 gene

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Grazia Bossi ◽  
Giuseppe Giordano ◽  
Gaetana Anna Rispoli ◽  
Giuseppe Maggiore ◽  
Mauro Naturale ◽  
...  
Keyword(s):  
Bile Acid ◽  
Replacement Therapy ◽  
Cholic Acid ◽  
Novel Mutation ◽  
Failure To Thrive ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Ionization Mass ◽  
Fast Atom Bombardment Ionization ◽  
Atypical Clinical Presentation

We report definitive diagnosis and effective treatment with oral cholic acid in one Italian male child affected by 3β- hydroxy-Δ5-C27-steroid dehydrogenase (3β- HSD) deficiency. He presented with failure to thrive, hepatomegaly and multiple cystic images in kidneys; no biochemical evidence of cholestasis. Large amounts of bile acid metabolites was detected in urine by fast atom bombardment ionization mass spectrometry (FAB-MS). <em>HSDH3B7</em> gene analysis identified one mutation in intron 4, at nucleotide 432, G&gt;A substitution that has never been reported before.The replacement therapy with oral cholic acid started early after the diagnosis and is still ongoing. Three years later hepatomegaly is no longer evident, liver function is normal and the child is growing regularly. In our experience, clinical features of 3β-HSD deficiency can be very poor and even cholestasis can lack at diagnosis. Early replacement therapy with cholic acid is safe and leads to clinical and biochemical control of the disease.

scholarly journals Feedback regulation of bile acid synthesis in primary human hepatocytes: Evidence that CDCA is the strongest inhibitor

Hepatology ◽  
2003 ◽  
Vol 38 (4) ◽  
pp. 930-938 ◽  
Author(s):  
Ewa Ellis ◽  
Magnus Axelson ◽  
Anna Abrahamsson ◽  
Gösta Eggertsen ◽  
Anders Thörne, ◽  
...  
Keyword(s):  
Bile Acid ◽  
Feedback Regulation ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Human Hepatocytes ◽  
Primary Human Hepatocytes

scholarly journals Cholic acid mediates negative feedback regulation of bile acid synthesis in mice

2002 ◽  
Vol 110 (8) ◽  
pp. 1191-1200 ◽  
Author(s):  
Jia Li-Hawkins ◽  
Mats Gåfvels ◽  
Maria Olin ◽  
Erik G. Lund ◽  
Ulla Andersson ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Negative Feedback ◽  
Feedback Regulation ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Negative Feedback Regulation

scholarly journals Nuclear and cytosolic distribution of conjugated cholic acid and radiolabelled glycocholic acid in rat liver

1979 ◽  
Vol 178 (1) ◽  
pp. 71-78 ◽  
Author(s):  
R C Strange ◽  
G J Beckett ◽  
I W Percy-Robb
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Rat Liver ◽  
Superior Mesenteric Vein ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Acid Receptor ◽  
Glycocholic Acid ◽  
Bile Acid Receptor

1. Normally fed and cholestyramine-treated rats were injected through the superior mesenteric vein with different amounts of radiolabelled glycoholic acid and the appearance of radioactivity in bile was measured. 2. In normally fed rats radioactivity appeared in bile within 30 s of injection and reached a maximum after 2 1/2 min; in the cholestyramine-treated animals the appearance of radioactivity was slower and less of the injected material was excreted into bile. 3. At 10 min after injection, livers were removed and the amounts of radioactive glycoholic acid and endogenous cholic acid conjugates in nuclei and cytosol were determined; most of the bile acid was found in the cytosol, only small amounts being found in nuclei. 4. Nuclear preparations from both normally fed and cholestyramine-fed rats were extracted with KCl (0.4 M) in an attempt to identify a putative bile acid receptor, but no such receptor was found. 5. Regulation of bile acid synthesis does not involve nuclear binding of bile acids.

Oral Cholic Acid for Hereditary Defects of Primary Bile Acid Synthesis: A Safe and Effective Long-term Therapy

2009 ◽  
Vol 137 (4) ◽  
pp. 1310-1320.e3 ◽  
Author(s):  
Emmanuel Gonzales ◽  
Marie F. Gerhardt ◽  
Monique Fabre ◽  
Kenneth D.R. Setchell ◽  
Anne Davit–Spraul ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Term Therapy ◽  
Long Term Therapy ◽  
Primary Bile Acid

scholarly journals Human liver cholesteryl ester hydrolase: cloning, molecular characterization, and role in cellular cholesterol homeostasis

2005 ◽  
Vol 23 (3) ◽  
pp. 304-310 ◽  
Author(s):  
Bin Zhao ◽  
Ramesh Natarajan ◽  
Shobha Ghosh
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Human Liver ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Human Hepatocytes ◽  
Cholesterol Homeostasis ◽  
Cholesteryl Esters ◽  
Ester Hydrolase ◽  
Hydrolysis Of

The liver regulates cholesterol homeostasis and eliminates excess cholesterol as bile acids or biliary cholesterol. Free cholesterol for bile acid synthesis or biliary secretion is obtained by the hydrolysis of stored cholesteryl esters or from cholesteryl esters taken up by the liver from high-density lipoproteins via a selective uptake pathway. The present study was undertaken to characterize the enzyme catalyzing this reaction, namely, cholesterol ester hydrolase (CEH) from the human liver, and demonstrate its role in regulating bile acid synthesis. Two cDNAs were isolated from the human liver that differed only in the presence of an additional alanine at position 18 in one of the clones. Transient transfection of COS-7 cells with a eukaryotic expression vector containing either of these two cDNAs resulted in significant increase in the hydrolysis of cholesteryl esters, authenticating these clones as human liver CEH. CEH mRNA and protein expression in human hepatocytes were demonstrated by real-time PCR and Western blot analyses, respectively, confirming the location of this enzyme in the cell type involved in hepatic cholesterol homeostasis. Overexpression of these CEH clones in human hepatocytes resulted in significant increase in bile acid synthesis, demonstrating a role for liver CEH in modulating bile acid synthesis. This CEH gene mapped on human chromosome 16, and the two clones represent two different transcript variants resulting from splice shifts at exon 1. In conclusion, these data identify that human liver CEH was expressed in hepatocytes, where it potentially regulates the synthesis of bile acids and thus the removal of cholesterol from the body.

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