Cited by 166Estrogen and related hormone effectsAdrenal Hormones and DisordersStress Responses and Cortisol

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Glucocorticoid receptor action in beneficial and side effects of steroid therapy: Lessons from conditional knockout mice

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Kleiman, Anna, Tuckermann, Jan P.·2007·Molecular and Cellular Endocrinology

DOI 10.1016/j.mce.2007.05.009

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Abstract

Glucocorticoids (GCs) are potent immune suppressive drugs with unfortunately severe side effects. Different molecular modes of actions of the GC receptor (GR) have been identified. Transcriptional transactivation by binding of a dimerized GR protein complex to the promoter of GC regulated genes or interference with activity of pro-inflammatory transcription factors by GR monomers are considered as the two major mechanisms. It has been hypothesized that selective GR agonists (SEGRAs) addressing dimer-independent function would reveal potent steroid therapeutic activity with reduced side effects. Recent studies of a mouse knock-in strain with a dimerization-deficient GR demonstrate that some inflammatory processes can be suppressed by GCs, while others cannot. Also side effects of GCs occur in these mice. Thus, depending on the process that is treated, SEGRA could be therapeutically more or less effective and not all side effects of steroid therapy may be reduced.

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Authors: Kleiman, A., & Tuckermann, J. P.
Affiliations: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
Corresponding author: Tuckermann, Jan P.
ORCID: Kleiman, Anna
Tuckermann, Jan P.
Venue: Molecular and Cellular Endocrinology
Publisher: Elsevier BV
Published: 2007-09
Volume: 275
Issue: 1-2
Pages: 98-108
ISSN: 0303-7207 (ISSN-L)
DOI: 10.1016/j.mce.2007.05.009
OpenAlex: W2086871852
Cited by: 165
References: 118
Citations by year: 2026: 3 · 2025: 6 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 12 · 2018: 8 · 2017: 5 · 2016: 8 · 2015: 14 · 2014: 12 · 2013: 13 · 2012: 14
FWCI: 0.87
Type: journal article
Language: en
Open access: green
hal.science
Licence: other-oa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular and Cellular Endocrinology (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: glucocorticoid receptor, glucocorticoids, selective glucocorticoid receptor agonists, conditional knockout mice, transcriptional activation, immunosuppression, inflammation
MeSH terms: Animals, Gene Expression Regulation, Glucocorticoids, Inflammation, Receptors, Glucocorticoid, Mice, Knockout, Receptor Cross-Talk, Mice

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Glucocorticoid receptor action in beneficial and side effects of steroid therapy: Lessons from conditional knockout mice

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