ArticleThe Journal of pharmacology and experimental therapeutics2017
Mechanistic Multi-Tissue Modeling of Glucocorticoid-Induced Leucine Zipper Regulation: Integrating Circadian Gene Expression with Receptor-Mediated Corticosteroid Pharmacodynamics.
Article in The Journal of pharmacology and experimental therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Physiologically-based modeling of methylprednisolone pharmacokinetics across species with extrapolations to humans.Journal of pharmaceutical sciences · 2025Article
- Physiologically Based Pharmacokinetic Modeling: The Reversible Metabolism and Tissue-Specific Partitioning of Methylprednisolone and Methylprednisone in Rats.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Circadian rhythms: influence on physiology, pharmacology, and therapeutic interventions.Journal of pharmacokinetics and pharmacodynamics · 2021Review
- Transitioning from Basic toward Systems Pharmacodynamic Models: Lessons from Corticosteroids.Pharmacological reviews · 2020Review
- Modeling Corticosteroid Pharmacokinetics and Pharmacodynamics, Part I: Determination and Prediction of Dexamethasone and Methylprednisolone Tissue Binding in the Rat.The Journal of pharmacology and experimental therapeutics · 2019Article
- Modeling Corticosteroid Pharmacokinetics and Pharmacodynamics, Part III: Estrous Cycle and Estrogen Receptor-Dependent Antagonism of Glucocorticoid-Induced Leucine Zipper (GILZ) Enhancement by Corticosteroids.The Journal of pharmacology and experimental therapeutics · 2019Article
- Modeling Corticosteroid Pharmacokinetics and Pharmacodynamics, Part II: Sex Differences in Methylprednisolone Pharmacokinetics and Corticosterone Suppression.The Journal of pharmacology and experimental therapeutics · 2019Article
- Could GILZ Be the Answer to Glucocorticoid Toxicity in Lupus?Frontiers in immunology · 2019Review
- GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life.Frontiers in immunology · 2019Review
- Receptor/gene/protein-mediated signaling connects methylprednisolone exposure to metabolic and immune-related pharmacodynamic actions in liver.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Glucocorticoid-Induced Leucine Zipper: Fine-Tuning of Dendritic Cells Function.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The glucocorticoid-induced leucine zipper (GILZ) is an important mediator of anti-inflammatory corticosteroid action. The pharmacokinetic/pharmacodynamic/pharmacogenomic effects of acute and chronic methylprednisolone (MPL) dosing on the tissue-specific dynamics of GILZ expression were examined in rats. A mechanism-based model was developed to investigate and integrate the role of MPL and circadian rhythms on the transcriptional enhancement of GILZ in multiple tissues. Animals received a single 50-mg/kg intramuscular bolus or a 7-day 0.3-mg/kg/h subcutaneous infusion of MPL and were euthanized at several time points. An additional group of rats were euthanized at several times and served as 24-hour light/dark (circadian) controls. Plasma MPL and corticosterone concentrations were measured by high-performance liquid chromatography. The expression of GILZ and glucocorticoid receptor (GR) mRNA was quantified in tissues using quantitative real-time reverse-transcription polymerase chain reaction. The pharmacokinetics of MPL were described using a two-compartment model. Mild-to-robust circadian oscillations in GR and GILZ mRNA expression were characterized in muscle, lung, and adipose tissues and modeled using Fourier harmonic functions. Acute MPL dosing caused significant down-regulation (40%-80%) in GR mRNA and enhancement of GILZ mRNA expression (500%-1080%) in the tissues examined. While GILZ returned to its rhythmic baseline following acute dosing, a new steady-state was observed upon enhancement by chronic dosing. The model captured the complex dynamics in all tissues for both dosing regimens. The model quantitatively integrates physiologic mechanisms, such as circadian processes and GR tolerance phenomena, which control the tissue-specific regulation of GILZ by corticosteroids. These studies characterize GILZ as a pharmacodynamic marker of corticosteroid actions in several tissues.
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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.