ArticleFrontiers in pharmacology2021
Pregnancy-Related Hormones Increase UGT1A1-Mediated Labetalol Metabolism in Human Hepatocytes.
Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Hepatotoxicity Associated with Labetalol Use: A Case Report with Systematic Review and Disproportionality Analysis Using FAERS.Journal of clinical pharmacology · 2026Pooled it
- Genetic variation on dolutegravir pharmacokinetics and relation to safety and efficacy outcomes: a systematic review.Pharmacogenomics · 2024Pooled it
- Cortisol drives pregnancy-associated induction of hepatic organic anion transporter 2, sodium/taurocholate cotransporting polypeptide, and organic cation transporter 1 in HepaRG cells through glucocorticoid receptor-, hepatocyte nuclear factor 1 alpha-, and hepatocyte nuclear factor 4 alpha-dependent signaling.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Altered Bile Acid Transport in Liver Disease.Biomedicines · 2026Review
- Lack of Modulation of In Vivo Activity of Organic Anion Transporters 1 and 3 in Pregnancy Using Furosemide as a Probe.Journal of clinical pharmacology · 2026Article
- Computational analysis and validation of UGT1A1/4 missense variants impacting tecovirimat metabolism in monkeypox patients.Frontiers in systems biology · 2026Article
- Liver-specific enhancers evolved from independent episodes of MITE domestication in Xenopus tropicalis.Mobile DNA · 2025Article
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- Pharmacokinetic Characterization of Labetalol in Pregnancy (The CLIP Study): A Prospective Observational Longitudinal Pharmacokinetic/Pharmacodynamic Cohort Study During Pregnancy and Postpartum.Journal of clinical medicine · 2025Article
- Mechanisms of altered hepatic drug disposition during pregnancy: small molecules.Expert opinion on drug metabolism & toxicology · 2025Review
- The effect of pregnancy-related hormones on hepatic transporters: studies with premenopausal human hepatocytes.Frontiers in pharmacology · 2024Article
- Pregnancy related hormones increase CYP3A mediated buprenorphine metabolism in human hepatocytes: a comparison to CYP3A substrates nifedipine and midazolam.Frontiers in pharmacology · 2023Article
- Direct antiviral agents (DAAs) and their use in pregnant women with hepatitis C (HCV).Expert review of anti-infective therapy · 2022Review
- The Role of Sex in Acute and Chronic Liver Damage.International journal of molecular sciences · 2022Review
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- Impact of pregnancy related hormones on drug metabolizing enzyme and transport protein concentrations in human hepatocytes.Frontiers in pharmacology · 2022Article
- The Impact of Pregnancy on Antihypertensive Drug Metabolism and Pharmacokinetics: Current Status and Future Directions.Expert opinion on drug metabolism & toxicology · 2021Review
- The impact of pregnancy and associated hormones on the pharmacokinetics of ΔExpert opinion on drug metabolism & toxicologyReview
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Pregnancy-related hormones (PRH) are recognized as important regulators of hepatic cytochrome P450 enzyme expression and function. However, the impact of PRH on the hepatic expression and function of uridine diphosphate glucuronosyltransferases (UGTs) remains unclear. Using primary human hepatocytes, we evaluated the effect of PRH exposure on mRNA levels and protein concentrations of UGT1A1, UGT2B7, and other key UGT enzymes, and on the metabolism of labetalol (a UGT1A1 and UGT2B7 substrate commonly prescribed to treat hypertensive disorders of pregnancy). Sandwich-cultured human hepatocytes (SCHH) from female donors were exposed to the PRH estradiol, estriol, estetrol, progesterone, and cortisol individually or in combination. We quantified protein concentrations of UGT1A1, UGT2B7, and four additional UGT1A isoforms in SCHH membrane fractions and evaluated the metabolism of labetalol to its glucuronide metabolites in SCHH. PRH exposure increased mRNA levels and protein concentrations of UGT1A1 and UGT1A4 in SCHH. PRH exposure also significantly increased labetalol metabolism to its UGT1A1-derived glucuronide metabolite in a concentration-dependent manner, which positively correlated with PRH-induced changes in UGT1A1 protein concentrations. In contrast, PRH did not alter UGT2B7 mRNA levels or protein concentrations in SCHH, and formation of the UGT2B7-derived labetalol glucuronide metabolite was decreased following PRH exposure. Our findings demonstrate that PRH alter expression and function of UGT proteins in an isoform-specific manner and increase UGT1A1-mediated labetalol metabolism in human hepatocytes by inducing UGT1A1 protein concentrations. These results provide mechanistic insight into the increases in labetalol clearance observed in pregnant individuals.
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What Socratic 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 Socratic graph.