ArticleScientific reports2020
Nuclear receptor CAR-ERα signaling regulates the estrogen sulfotransferase gene in the liver.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- CAR: Discovery and development by the pharmacogenetics laboratory at NIEHS, NIH.Pharmacological research · 2025Review
- Estrogen associations with human pregnancy related increases in cytochrome P450 3A activity.Frontiers in pharmacology · 2025Article
- Isoform-level expression of the constitutive androstane receptor (CAR or NR1I3) transcription factor better predicts the mRNA expression of the cytochrome P450s in human liver samples.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Hepatic Gene Expression and Metabolite Profiles of Androstenone and Skatole Relative to Plasma Estrone Sulfate Levels in Boars.Biomolecules · 2024Article
- Monkey multi-organ cell atlas exposed to estrogen.Life medicine · 2024Article
- Investigation of dichlorodiphenyltrichloroethane (DDT) on xenobiotic enzyme disruption and metabolomic bile acid biosynthesis in DDT-sprayed areas using wild rats.The Journal of veterinary medical science · 2023Article
- Phenobarbital in Nuclear Receptor Activation: An Update.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Candidate Proficiency Test Chemicals to Address Industrial Chemical Applicability Domains forFrontiers in toxicology · 2022Review
- Sex-specific expression mechanism of hepatic estrogen inactivating enzyme and transporters in diabetic women.Biochemical pharmacology · 2021Article
- Estrogen Sulfotransferase (SULT1E1): Its Molecular Regulation, Polymorphisms, and Clinical Perspectives.Journal of personalized medicine · 2021Review
- Nuclear receptor phosphorylation in xenobiotic signal transduction.The Journal of biological chemistry · 2020Review
- RORα phosphorylation by casein kinase 1α as glucose signal to regulate estrogen sulfation in human liver cells.The Biochemical journal · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Estrogen sulfotransferase (SULT1E1) inactivates estrogen and regulates its metabolic homeostats. Whereas SULT1E1 is expressed low in the liver of adult mice, it is induced by phenobarbital (PB) treatment or spontaneously in diabetic livers via nuclear receptors. Utilizing constitutive active/androstane receptor (CAR) KO, estrogen receptor α (ERα KO, phosphorylation-blocked ERα S216A KI mice, it is now demonstrated that, after being activated by PB, CAR binds and recruits ERα onto the Sulte1 promoter for subsequent phosphorylation at Ser216. This phosphorylation tightens CAR interacting with ERα and to activates the promoter. Hepatic SULT1E1 mRNA levels are constitutively up-regulated in type 1 diabetic Akita mice; CAR spontaneously accumulates in the nucleus and activates the Sult1e1 promoter by recruiting phosphorylated ERα in the liver as observed with PB-induced livers. Thus, this CAR-phosphorylated ERα signaling enables these two nuclear receptors to communicate, activating the Sult1e1 gene in response to either PB or diabetes in mice. ERα phosphorylation may integrate CAR into estrogen actions, providing insights into understanding drug-hormone interactions in clinical therapy.
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