Molecular mechanisms of glucocorticoid action: what is important?

Newton, Robert

doi:10.1136/thorax.55.7.603

Cited by 453 publications

(394 citation statements)

References 138 publications

(80 reference statements)

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“…In the context of glucocorticoids, reduced expression of multiple inflammatory genes is central to anti-inflammatory activity (25). However, increased DUSP1 expression is often considered as a key anti-inflammatory effector mechanism (23,26), yet this appears inconsistent with the above idea that MAPKs increase ZFP36 to increase feed-forward control of inflammatory genes.…”

contrasting

confidence: 42%

Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual-specificity Phosphatase 1 (DUSP1)

Shah

Mostafa

McWhae

et al. 2016

Journal of Biological Chemistry

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Background: ZFP36 negatively regulates AU-rich element-containing mRNAs. Results: DUSP1 silencing increases ZFP36 expression and enhances negative feed-forward control of TNF. Conclusion: MAPK inhibition initially attenuates TNF mRNA, but reduced feed-forward control subsequently produces an increase. Significance: Understanding such networks is essential to develop novel anti-inflammatory therapies or understand TNF repression by glucocorticoids, which may not require DUSP1 or ZFP36 expression.

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contrasting

confidence: 42%

Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual-specificity Phosphatase 1 (DUSP1)

Shah

Mostafa

McWhae

et al. 2016

Journal of Biological Chemistry

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“…Animals (3-4 per time point) were sacrificed over a period of 72 hr for the single dose groups (0.25, 0.5, 0.75, 1, 2, 4, 5, 5. 5,6,7,8,12,18,24,30,36, 48 and 72 hr) and over a period of 120 hr (0. 25, 1, 3, 5, 6, 7, 8, 12, 18, 24, 24.25, 25, 27, 29, 30, 31, 32, 36, 42, 54, 72, 96 and 120 hr) for the dual dose group.…”

Section: Methodsmentioning

confidence: 99%

Assessing the Dynamics of Nuclear Glucocorticoid-Receptor Complex: Adding Flexibility to Gene Expression Modeling

Hazra

DuBois

Almon

et al. 2007

J Pharmacokinet Pharmacodyn

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A retrospective analysis was performed to modify our fourth-generation pharmacodynamic model for glucocorticoid receptor (GR) dynamics with incorporation of more physiological features. This modified model was developed by integrating previously reported free cytosolic GR and GR mRNA data following single (10, 50 mg/kg) and dual (50 mg/kg at 0 and 24 hr) intravenous doses of methylprednisolone (MPL) in adrenalectomized (ADX) male Wistar rats with several in vitro studies describing real-time kinetics of the transfer of rat steroid-receptor complex from the cell cytosol to the nucleus. Additionally, free hepatic cytosolic GR and its mRNA data from a chronic infusion dosing study of MPL (0.1 and 0.3 mg/kg/hr) in male ADX Wistar rats were used to verify the predictability of the model. Incorporation of information regarding in vitro receptor kinetics allowed us to describe the receptor-mediated pharmacogenomic effects of MPL for a larger variety of genes in rat liver from microarray studies. These included early responsive gene like CCAAT/ enhancer binding protein-β (CEBP-β), a transcription factor, as well as the later responsive gene for tyrosine aminotransferase (TAT), a classical biomarker of glucocorticoid (GC) genomic effects. This more mechanistic model of GR dynamics can be applied to characterize profiles for a greater number of genes in liver.

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“…Thus, GCs display an intrinsic control of both CRH and AVP activity, including ACTH secretion from corticotrophs [99] . Genomic actions of GCs are mediated by the transcriptional activation or repression of target genes after translocation of the intracellular (ligandbound) receptor to the nucleus and binding of the receptor complex to a GC response element sequence located in the promoter region of GC-regulated genes [84,[100][101] . …”

mentioning

confidence: 99%

Hypothalamic-pituitary-adrenal axis function during perinatal depression

et al. 2015

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Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis is an important pathological finding in pregnant women exhibiting major depressive disorder. They show high levels of cortisol proinflammatory cytokines, hypothalamic-pituitary peptide hormones and catecholamines, along with low dehydroepiandrosterone levels in plasma. During pregnancy, the TH2 balance together with the immune system and placental factors play crucial roles in the development of the fetal allograft to full term. These factors, when altered, may generate a persistent dysfunction of the HPA axis that may lead to an overt transfer of cortisol and toxicity to the fetus at the expense of reduced activity of placental 11β-hydroxysteroid dehydrogenase type 2. Epigenetic modifications also may contribute to the dysregulation of the HPA axis. Affective disorders in pregnant women should be taken seriously, and therapies focused on preventing the deleterious effects of stressors should be implemented to promote the welfare of both mother and baby.Keywords: brain; depression; neuroendocrine; pregnancy; stress; glucocorticoids Extensive studies have demonstrated that early life stressors produce changes in behavior and enhance the sensitivity of the stress response systems [1][2][3][4] . Although the genetic background has been implicated in the development of mood-related disorders, and genetic research has identified some chromosomal regions and genes that are involved in susceptibility to mood disorders, the etiology of anxiety and depressive disorders is still not clear in humans, particularly in women with major depressive disorder (MDD) [1] .The pathogenesis of perinatal depression is an emerging field. Although considerable progress has been made in this area in the last few years, there still remain unanswered questions and gaps in our knowledge of the underlying pathogenesis, the long-term impact of perinatal depression on the developing fetus, and the best methods for counseling pregnant women concerning the risks of untreated MDD versus the risks of psychopharmacologic treatment during pregnancy and lactation [5] . Meta-analysis studies have reported that the mean prevalence rate of prenatal depression is ~12% (this varies greatly according to location, mode of assessment, and socioeconomic conditions), and show that a large percentage of pregnant women displaying major depression remain depressed in the postpartum period and/or continuously [6,7] . Anxiety, depressive disorder, and stress during pregnancy are risk Phillipe Leff Gelman, et al. HPA axis in perinatal depression 339 factors for negative outcomes in newborns, like preterm birth or low birth weight; also, insecure attachment and impaired child development could be a consequence of mental disorders during pregnancy [6,[8][9][10] . The mechanisms by which maternal depression impacts fetal and neonatal development are currently under investigation; there is some evidence that depressive symptoms impact the infant's hypothalamic-pituitary-adrenal (HPA) axis, enhancing the ...

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Molecular mechanisms of glucocorticoid action: what is important?

Cited by 453 publications

References 138 publications

Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual-specificity Phosphatase 1 (DUSP1)

Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual-specificity Phosphatase 1 (DUSP1)

Assessing the Dynamics of Nuclear Glucocorticoid-Receptor Complex: Adding Flexibility to Gene Expression Modeling

Hypothalamic-pituitary-adrenal axis function during perinatal depression

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