Related Experiment Video

Updated: Apr 17, 2026

Human Liver Spheroids from Peripheral Blood for Liver Disease Studies
09:51

Human Liver Spheroids from Peripheral Blood for Liver Disease Studies

Published on: January 27, 2023

2.4K

Expression of CYP3A4 and CYP3A7 in Human Foetal Tissues and its Correlation with Nuclear Receptors

Stina Betts1, Linda Björkhem-Bergman2, Anders Rane1

  • 1Division of Clinical Pharmacology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Basic & Clinical Pharmacology & Toxicology
|February 18, 2015
PubMed

Insights

Nuclear receptors like VDR, PPARα, PXR, and CAR influence fetal CYP3A4 and CYP3A7 gene expression, particularly in the liver. Genetic variations in these receptors did not correlate with CYP3A4/CYP3A7 levels, but VDR polymorphisms affected VDR expression.

Area of Science:

  • Pharmacology
  • Developmental Biology
  • Genetics

Background:

  • Nuclear receptors, including vitamin D receptor (VDR), peroxisome proliferator-activated receptor α (PPARα), pregnane X receptor (PXR), and constitutive androstane receptor (CAR), are known to regulate drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 expression in adults.
  • Understanding these regulatory mechanisms in fetal development is crucial for predicting drug metabolism and potential toxicities during early life stages.

Purpose of the Study:

  • To investigate the gene expression of fetal CYP3A4 and CYP3A7 in human fetal tissues.
  • To examine the relationship between the expression of nuclear receptors (VDR, PPARα, PXR, CAR) and the gene expression of CYP3A4 and CYP3A7 in fetal tissues.
  • To explore the impact of genetic variations in these nuclear receptors on CYP3A4 and CYP3A7 expression.

Main Methods:

  • Quantitative PCR was used to determine the relative expression of CYP3A4, CYP3A7, and the nuclear receptors VDR, PPARα, PXR, and CAR in fetal livers, intestines, and adrenals.
  • Adult liver samples were also analyzed for enzyme expression.
  • Genetic polymorphisms in VDR, PXR, and PPARα genes were assessed for their correlation with CYP3A4 and CYP3A7 expression.

Main Results:

  • Significant interindividual variability was observed in both CYP3A4 (49-fold) and CYP3A7 (326-fold) expression, with highest levels in the liver.
  • Significant correlations were found between the expression of studied nuclear receptors and CYP3A4/CYP3A7 expression in fetal liver, and CYP3A4 in fetal intestine (p < 0.001).
  • No correlation was found between specific VDR, PXR, or PPARα gene polymorphisms and CYP3A4/CYP3A7 expression, although VDR polymorphisms affected VDR gene expression.

Conclusions:

  • Differences in nuclear receptor expression levels are likely key drivers of the observed variability in fetal CYP3A4 and CYP3A7 expression.
  • While specific genetic variations tested did not directly correlate with CYP3A4/CYP3A7 expression, the impact of polymorphisms on receptor expression warrants further investigation.
  • These findings highlight the complex regulation of fetal drug metabolism enzymes and their potential variability.

More Related Videos

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

13.3K
Murine Fetal Echocardiography08:04

Murine Fetal Echocardiography

Published on: February 15, 2013

18.3K

Related Concept Videos

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450...
257
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
6.4K
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
362
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
17.4K