ArticleDrug metabolism and disposition: the biological fate of chemicals2014
Human placental lactogen induces CYP2E1 expression via PI 3-kinase pathway in female human hepatocytes.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review.PLoS medicine · 2016Pooled it
- Pregnancy-induced changes in the pharmacokinetics of caffeine and its metabolites.Journal of clinical pharmacology · 2016Trial
- Mechanisms of altered hepatic drug disposition during pregnancy: small molecules.Expert opinion on drug metabolism & toxicology · 2025Review
- Article
- Pregnancy-Related Hormones Increase UGT1A1-Mediated Labetalol Metabolism in Human Hepatocytes.Frontiers in pharmacology · 2021Article
- Pregnancy-Related Hormones Increase Nifedipine Metabolism in Human Hepatocytes by Inducing CYP3A4 Expression.Journal of pharmaceutical sciences · 2021Article
- Cytochrome P450 2E1 and its roles in disease.Chemico-biological interactions · 2020Review
- Methods to study mechanisms underlying altered hepatic drug elimination during pregnancy.Seminars in perinatology · 2020Review
- Physiologically Based Pharmacokinetic Modeling to Characterize Acetaminophen Pharmacokinetics and N-Acetyl-p-Benzoquinone Imine (NAPQI) Formation in Non-Pregnant and Pregnant Women.Clinical pharmacokinetics · 2020Article
- Physiological Regulation of Drug Metabolism and Transport: Pregnancy, Microbiome, Inflammation, Infection, and Fasting.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Establishment and characterization of feeder cell-dependent bovine fetal liver cell lines.In vitro cellular & developmental biology. Animal · 2016Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The state of pregnancy is known to alter hepatic drug metabolism. Hormones that rise during pregnancy are potentially responsible for the changes. Here we report the effects of prolactin (PRL), placental lactogen (PL), and growth hormone variant (GH-v) on expression of major hepatic cytochromes P450 expression and a potential molecular mechanism underlying CYP2E1 induction by PL. In female human hepatocytes, PRL and GH-v showed either no effect or small and variable effects on mRNA expression of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, and 3A5. On the other hand, PL increased expression level of CYP2E1 mRNA with corresponding increases in CYP2E1 protein and activity levels. Results from hepatocytes and HepaRG cells indicate that PL does not affect the expression or activity of HNF1α, the known transcriptional activator of basal CYP2E1 expression. Furthermore, transient transfection studies and Western blot results showed that STAT signaling, the previously known mediator of PL actions in certain tissues, does not play a role in CYP2E1 induction by PL. A chemical inhibitor of PI3-kinase signaling significantly repressed the CYP2E1 induction by PL in human hepatocytes, suggesting involvement of PI3-kinase pathway in CYP2E1 regulation by PL. CYP2E1-humanized mice did not exhibit enhanced CYP2E1 expression during pregnancy, potentially because of interspecies differences in PL physiology. Taken together, these results indicate that PL induces CYP2E1 expression via PI3-kinase pathway in human hepatocytes.
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