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

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

Open access
Kleiman, Anna, Tuckermann, Jan P.·2007·Molecular and Cellular Endocrinology
DOI 10.1016/j.mce.2007.05.009
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1016/j.mce.2007.05.009

Cites

120 of 120 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Chronic exposure to glucocorticoids results in adverse side effects such as osteoporosis, diabetes, hypertension, dyslipidemia, and neurodegeneration.

    “As a matter of fact, chronic exposure to GCs results in various adverse side effects such as osteoporosis, diabetes, hypertension, dyslipidemia, and even neurodegeneration (5, 22).”

    From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [22]

  • The non-liganded GR-α is sequestered in the cytoplasm by a multiprotein chaperone complex; ligand binding causes conformational change, chaperone dissociation, nuclear localization signal unmasking, and nuclear translocation where it modulates gene expression.

    “The non-liganded GR-α is sequestered in the cytoplasm by a multiprotein complex that may be composed of heat-shock protein (HSP) 90, 70, 56, or 40, as well as co-chaperones p23, p60, Src kinase, and immunophilins FKBP51, 52 (22, 75, 79). These cytoplasmic chaperones conceal the nuclear localization signal (NLS) of the steroid receptor and thereby preclude its shuttling to the nucleus. Importantly,”

    From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [22]

  • Differential expression of transcription factors, co-activators, co-repressors, and other binding partners is critical in tailoring the actions of GCs through the GR.

    “In similar fashion, the differential expression of transcription factors, co-activators, co-repressors, and other binding partners are critical in tailoring the actions of GCs through the GR (22).”

    From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [22]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kleiman, A., & Tuckermann, J. P.
Affiliations
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
Corresponding author
Tuckermann, Jan P.
ORCID
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
Licence
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 › Genetics › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review