The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction
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1. Urinary excretion of 6 beta-hydroxycortisol, hepatic microsomal cortisol 6 beta-hydroxylase and the specific content of several forms of cytochrome P450 were measured in 8 to 14 patients before and after treatment with rifampicin (600 mg orally per day for 4 days). 2. Rifampicin treatment produced an average five fold increase in daily excretion of urinary 6 beta-hydroxycortisol. 3. Cortisol 6 beta-hydroxylase activity increased from 15 +/- 6 pmol min-1 mg-1 in organ donors (considered as 'control subjects') to 87 +/- 31 pmol min-1 mg-1 in rifampicin treated patients. 4. Among three forms of human P450 (P450IA, IIC and IIIA), (1), (2), measured by Western blots, only P450IIIA was significantly induced by the antibiotic. 5. Only antibodies against P450IIIA selectively inhibited cortisol 6 beta-hydroxylase in human liver microsomes. 6. Cortisol 6 beta-hydroxylase was correlated with P450IIIA specific content. 7. The urinary level of 6 beta-hydroxycortisol correlated with liver microsomal cortisol 6 beta-hydroxylase and P450IIIA specific content. 8. We conclude that P450IIIA is predominantly responsible for cortisol 6 beta-hydroxylase activity in human liver microsomes and that urinary 6 beta-hydroxycortisol is a marker of the induction of this cytochrome P450.
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Cortisol can be 6β-hydroxylated by CYP3A4 expressed in the liver, resulting in 6β-hydroxycortisol (6β-OHF).
“Cortisol can also be 6β-hydroxylated by CYP3A4 expressed in the liver, resulting in 6β-hydroxycortisol (6β-OHF) [259,260].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [259]
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- Authors
- Ged, C., Rouillon, J., Pichard, L., Combalbert, J., Bressot, N., Bories, P., Michel, H., Beaune, P., & Maurel, P.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 1989-10
- Volume
- 28
- Issue
- 4
- Pages
- 373-387
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC1379986
- OpenAlex
- W1988858173
- Cited by
- 333
- References
- 69
- Citations by year
- 2026: 4 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 2 · 2019: 6 · 2018: 4 · 2017: 1 · 2016: 6 · 2015: 4 · 2014: 7 · 2013: 5 · 2012: 10
- FWCI
- 14.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- urinary excretion, hepatic microsomal enzyme induction, rifampicin, liver microsomes, drug-induced enzyme induction
- MeSH terms
- Adult, Aged, Chromatography, High Pressure Liquid, Cytochrome P-450 Enzyme System, Enzyme Induction, Female, Humans, Hydrocortisone, Mixed Function Oxygenases, Isoenzymes, Liver, Male, Microsomes, Liver, Middle Aged, Rifampin, Tissue Donors, Immunoblotting, Biomarkers
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