ArticleToxicology2009
Sexually dimorphic regulation and induction of P450s by the constitutive androstane receptor (CAR).
Article in Toxicology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 82 citations in OpenAlex.
- Influence of sex on propofol metabolism, a pilot study: implications for propofol anesthesia.European journal of clinical pharmacology · 2012Trial
- DSS Colitis Model: Traps, Tricks, and Reporting Recommendations.Biomedicines · 2026Review
- Sex-dependent modulation of PCB-mediated toxicity from a proteomic and microbiome perspective.Scientific reports · 2025Article
- CAR: Discovery and development by the pharmacogenetics laboratory at NIEHS, NIH.Pharmacological research · 2025Review
- Impact of sex and pregnancy on hepatic CYP3A4 expression and activity in a humanized mouse model.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Safety and efficacy of a feed additive consisting of a dry extract obtained from the leaves ofEFSA journal. European Food Safety Authority · 2024Article
- The relationship between gender and pharmacology.Current research in pharmacology and drug discovery · 2024Article
- Pharmacological activation of constitutive androstane receptor induces female-specific modulation of hepatic metabolism.JHEP reports : innovation in hepatology · 2024Article
- Evaluation of Sex Differences in Preclinical Pharmacology Research: How Far Is Left to Go?Pharmaceuticals (Basel, Switzerland) · 2023Review
- Regulation of Nuclear Receptors PXR and CAR by Small Molecules and Signal Crosstalk: Roles in Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Constitutive Androstane Receptor Agonist, TCPOBOP: Maternal Exposure Impairs the Growth and Development of Female Offspring in Mice.International journal of molecular sciences · 2023Article
- Review
- Interplay Between GH-regulated, Sex-biased Liver Transcriptome and Hepatic Zonation Revealed by Single-Nucleus RNA Sequencing.Endocrinology · 2022Article
- Butyrate Treatment of DSS-Induced Ulcerative Colitis Affects the Hepatic Drug Metabolism in Mice.Frontiers in pharmacology · 2022Article
- The Person's Care Requires a Sex and Gender Approach.Journal of clinical medicine · 2021Review
- Sex- and Gender-Based Pharmacological Response to Drugs.Pharmacological reviews · 2021Article
- Expression of cytochrome P450 isozyme transcripts and activities in human livers.Xenobiotica; the fate of foreign compounds in biological systems · 2021Article
- Constitutive Androstane Receptor: A Peripheral and a Neurovascular Stress or Environmental Sensor.Cells · 2020Review
- Review
- Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
The constitutive androstane receptor (CAR) is a xenosensing nuclear receptor and regulator of cytochrome P450s (CYPs). However, the role of CAR as a basal regulator of CYP expression nor its role in sexually dimorphic responses have been thoroughly studied. We investigated basal regulation and sexually dimorphic regulation and induction by the potent CAR activator TCPOBOP and the moderate CAR activator Nonylphenol (NP). NP is an environmental estrogen and one of the most commonly found environmental toxicants in Europe and the United States. Previous studies have demonstrated that NP induces several CYPs in a sexually dimorphic manner, however the role of CAR in regulating NP-mediated sexually dimorphic P450 expression and induction has not been elucidated. Therefore, wild-type and CAR-null male and female mice were treated with honey as a carrier, NP, or TCPOBOP and CYP expression monitored by QPCR and Western blotting. CAR basally regulates the expression of Cyp2c29, Cyp2b13, and potentially Cyp2b10 as demonstrated by QPCR. Furthermore, we observed a shift in the testosterone 6alpha/15alpha-hydroxylase ratio in untreated CAR-null female mice to the male pattern, which indicates an alteration in androgen status and suggests a role for androgens as CAR inverse agonists. Xenobiotic-treatments with NP and TCPOBOP induced Cyp2b10, Cyp2c29, and Cyp3a11 in a CAR-mediated fashion; however NP only induced these CYPs in females and TCPOBOP induced these CYPs in both males and females. Interestingly, Cyp2a4, was only induced in wild-type male mice by TCPOBOP suggesting Cyp2a4 induction is not sensitive to CAR-mediated induction in females. Overall, TCPOBOP and NP show similar CYP induction profiles in females, but widely different profiles in males potentially related to lower sensitivity of males to either indirect or moderate CAR activators such as NP. In summary, CAR regulates the basal and chemically inducible expression of several sexually dimorphic xenobiotic metabolizing P450s in a manner that varies depending on the ligand.
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Registered trials
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.