Cited by 145Pharmacogenetics and Drug MetabolismEstrogen and related hormone effectsDrug Transport and Resistance Mechanisms

Steroid hormone biotransformation and xenobiotic induction of hepatic steroid metabolizing enzymes

You, Li·2004·Chemico-Biological Interactions

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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Crossref · 10.1016/j.cbi.2004.01.006

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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

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