ArticleMolecular pharmacology2015
Estrogen-Induced Cholestasis Leads to Repressed CYP2D6 Expression in CYP2D6-Humanized Mice.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Does In Vitro Cytochrome P450 Downregulation Translate to In Vivo Drug-Drug Interactions? Preclinical and Clinical Studies With 13-cis-Retinoic Acid.Clinical and translational science · 2019Trial
- Gly-βMCA modulates bile acid metabolism to reduce hepatobiliary injury inAmerican journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology.The American journal of pathology · 2025Review
- Effect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne.British journal of clinical pharmacology · 2024Article
- Mitigation of intrahepatic cholestasis induced by 17α-ethinylestradiol via nanoformulation of Silybum marianum L.BMC complementary medicine and therapies · 2024Article
- Novel Independent Trans- and Cis-Genetic Variants Associated with CYP2D6 Expression and Activity in Human Livers.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- The Pathological Mechanisms of Estrogen-Induced Cholestasis: Current Perspectives.Frontiers in pharmacology · 2021Review
- Determinants of Cytochrome P450 2D6 mRNA Levels in Healthy Human Liver Tissue.Clinical and translational science · 2019Article
- Sex Differences in Antidepressant Effect of Sertraline in Transgenic Mouse Models.Frontiers in cellular neuroscience · 2019Article
- P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- CYP2D6 Protein Level Is the Major Contributor to Interindividual Variability in CYP2D6-Mediated Drug Metabolism in Healthy Human Liver Tissue.Clinical pharmacology and therapeutics · 2018Article
- Ten Years' Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics.Journal of personalized medicine · 2018Review
- Chicken bile powder protects against α-naphthylisothiocyanate-induced cholestatic liver injury in mice.Oncotarget · 2017Article
- Cholic Acid Feeding Leads to Increased CYP2D6 Expression in CYP2D6-Humanized Mice.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Transcriptional Regulation of CYP2D6 Expression.Drug metabolism and disposition: the biological fate of chemicals · 2017Review
- Characterization of Atomoxetine Biotransformation and Implications for Development of PBPK Models for Dose Individualization in Children.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Interindividual Variability in Cytochrome P450-Mediated Drug Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cholestasis activates bile acid receptor farnesoid X receptor (FXR) and subsequently enhances hepatic expression of small heterodimer partner (SHP). We previously demonstrated that SHP represses the transactivation of cytochrome P450 2D6 (CYP2D6) promoter by hepatocyte nuclear factor (HNF) 4α. In this study, we investigated the effects of estrogen-induced cholestasis on CYP2D6 expression. Estrogen-induced cholestasis occurs in subjects receiving estrogen for contraception or hormone replacement, or in susceptible women during pregnancy. In CYP2D6-humanized transgenic (Tg-CYP2D6) mice, cholestasis triggered by administration of 17α-ethinylestradiol (EE2) at a high dose led to 2- to 3-fold decreases in CYP2D6 expression. This was accompanied by increased hepatic SHP expression and subsequent decreases in the recruitment of HNF4α to CYP2D6 promoter. Interestingly, estrogen-induced cholestasis also led to increased recruitment of estrogen receptor (ER) α, but not that of FXR, to Shp promoter, suggesting a predominant role of ERα in transcriptional regulation of SHP in estrogen-induced cholestasis. EE2 at a low dose (that does not cause cholestasis) also increased SHP (by ∼ 50%) and decreased CYP2D6 expression (by 1.5-fold) in Tg-CYP2D6 mice, the magnitude of differences being much smaller than that shown in EE2-induced cholestasis. Taken together, our data indicate that EE2-induced cholestasis increases SHP and represses CYP2D6 expression in Tg-CYP2D6 mice in part through ERα transactivation of Shp promoter.
Indexed as
Identifiers
What OpenQuestion holds
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.