ArticleBritish journal of pharmacology2013
Inherent sex-dependent regulation of human hepatic CYP3A5.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 30 citations in OpenAlex.
- Prolonged-Release Once-Daily Formulation of Tacrolimus Versus Standard-of-Care Tacrolimus inTransplant international : official journal of the European Society for Organ Transplantation · 2022Trial
- Potential Mechanisms Linking Excessive Testosterone to PMOS: Insights from Network Toxicology and Machine Learning.Metabolites · 2026Article
- Distribution of citalopram enantiomers following medication with racemic citalopram - a naturalistic therapeutic drug monitoring study.European journal of clinical pharmacology · 2026Article
- Sex differences in hepatic enzymes and transporters involved in pharmacokinetics.Liver research (Beijing, China) · 2025Review
- Ionic Liquid 1-Octyl-3-Methylimidazolium (M8OI) Is Mono-Oxygenated by CYP3A4 and CYP3A5 in Adult Human Liver.Journal of xenobiotics · 2024Article
- Impact of Switching From Immediate- or Prolonged-Release to Once-Daily Extended-Release Tacrolimus (LCPT) on Tremor in Stable Kidney Transplant Recipients: The Observational ELIT Study.Transplant international : official journal of the European Society for Organ Transplantation · 2024Observational
- Bioavailability and Pharmacokinetics of Endoxifen in Female Rats and Dogs: Evidence to Support the Use of Endoxifen to Overcome the Limitations of CYP2D6-Mediated Tamoxifen Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- 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
- Sex Differences in Clopidogrel Effects Among Young Patients With Acute Coronary Syndrome: A Role for Genetics?CJC open · 2022Article
- Early expression of requisite developmental growth hormone imprinted cytochromes P450 and dependent transcription factors.Endocrine connections · 2021Article
- Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice.International journal of environmental research and public health · 2020Article
- Sex Differences in Urate Handling.International journal of molecular sciences · 2020Review
- Feminization imprinted by developmental growth hormone.Molecular and cellular endocrinology · 2019Article
- Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with CYP3A5*3/*3.Biochemical genetics · 2017Article
- Donor CYP3A5 genotype influences tacrolimus disposition on the first day after paediatric liver transplantation.British journal of clinical pharmacology · 2017Article
- Biological sex themed section: incorporating the female dimension into cardiovascular pharmacology.British journal of pharmacology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeExpression of hepatic cytochromes P450 (CYP) in all species examined, including humans, is generally sexually dimorphic. We examined the sex-dependent expression of CYP3A5 and the hormone-regulated molecular mechanism(s) responsible for any dimorphism. EXPERIMENTAL APPROACH: CYP3A5 levels as well as nuclear translocation and promoter binding of transcription factors regulating CYP3A5 expression were measured in primary hepatocyte cultures derived from men and women exposed to physiological-like levels of growth hormone alone, dexamethasone alone and the combined regimen. KEY
resultsWe observed a dramatic inherent CYP3A5 sexual dimorphism (women > men) with all treatments as a result of a ~2-fold greater level of hormone-induced activation and nuclear accumulation of hepatocyte nuclear factor-4α (HNF-4α), pregnane X receptor (PXR) and retinoic X receptorα (RXRα) in female hepatocytes. Furthermore, PXR : RXRα exhibited significantly higher DNA binding levels to its specific binding motif on the CYP3A5 promoter in female hepatocytes, inferring a possible explanation for the elevated expression of the isoform in women. Results from experiments using HepG2 cells treated with siRNA-induced knockdown of HNF-4α and/or transfected with luciferase reporter constructs containing the CYP3A5 promoter were in agreement with the basic mechanism observed in primary hepatocytes of both sexes. CONCLUSIONS AND IMPLICATIONS: Female-predominant expression of human CYP3A5 is due to an inherent, sex-dependent suboptimal activation of the transcription networks responsible for hormone-induced expression of the isoform in men. Accordingly, in conjunction with previous studies of other human CYPs, men and women are intrinsically unlikely to handle many drugs in the same way; thus, sex should be a requisite component factored into the design of personalized drug therapies.
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.