Steroid hormone biotransformation and xenobiotic induction of hepatic steroid metabolizing enzymes
Abstract
Normal reproductive development depends on the interplay of steroid hormones with their receptors at specific tissue sites. The concentrations of hormone ligands in the circulation and at target sites are maintained through coordinated regulation on steroid biosynthesis and degradation. Changed bioavailability of steroids, through alteration of steroidogenesis or biotransformation rates, leads to changes in endocrine function. Steroid hormones lose their receptor reactivity in most cases when they are bound to binding proteins, while metabolic conversion can result in either active or inactive metabolites. Hydroxylation by cytochrome P450 (CYP) enzymes and conjugation with glucuronide and sulfate are among the major hepatic pathways of steroid inactivation. The expression of these biotransformation enzymes can be induced by many xenobiotics. The barbiturate phenobarbital and the environmental toxicant 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) are among the well characterized inducers for the CYP 2B and 3A enzymes and selected conjugation enzymes. The induction of the steroid biotransformation enzymes is partly mediated through the activation of a group of nuclear receptors including the glucocorticoid receptor, the constitutive androstane receptor (CAR), the pregnane X receptor (PXR), and the peroxisome proliferator activated receptors (PPAR). Drug or chemical-induced increases in hepatic enzyme activities are often a basis for drug-drug interactions that lead to enhanced elimination and reduced therapeutic efficacy of steroidal drugs. The effects of enzyme induction on endogenous steroid clearance, along with its possible consequence, are less well understood. While enzyme induction by xenobiotics may increase clearance of the endogenous steroid, regulatory mechanisms for steroid homeostasis may adapt and compensate for altered clearance.
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At least 17 hepatic CYPs potentially participate in the metabolism of steroids.
“with at least 17 hepatic CYPs potentially participating in the metabolism of steroids [[116], [117], [118]].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [118]
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- Authors
- You, L.
- Venue
- Chemico-Biological Interactions
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 147
- Issue
- 3
- Pages
- 233-246
- ISSN
- 0009-2797 (ISSN-L)
- OpenAlex
- W2016876126
- Cited by
- 145
- References
- 98
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 8 · 2016: 2 · 2015: 4 · 2014: 8 · 2013: 6 · 2012: 13
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemico-Biological Interactions (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Chemistry Council
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- xenobiotic induction, cytochrome P450, glucuronidation, sulfation, phenobarbital, DDE, CYP2B, CYP3A, nuclear receptors, glucocorticoid receptor, constitutive androstane receptor, pregnane X receptor, peroxisome proliferator-activated receptors, drug-drug interactions, steroid hormone receptors
- MeSH terms
- Animals, Biotransformation, Cytochrome P-450 Enzyme System, Enzyme Induction, Humans, Liver, Steroids, Xenobiotics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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