ArticleSteroids2019
Membrane-initiated nuclear trafficking of the glucocorticoid receptor in hypothalamic neurons.
Article in Steroids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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
20 citing papers in PubMed, 38 citations in OpenAlex.
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- Coping with the multifaceted and multifunctional role of cortisol in the brain.Neuroscience applied · 2024Review
- Immunoglobulin G inhibits glucocorticoid-induced osteoporosis through occupation of FcγRI.iScience · 2023Article
- Stress-induced glucocorticoid desensitizes adrenoreceptors to gate the neuroendocrine response to somatic stress in male mice.Cell reports · 2022Article
- Multiplexed Membrane Signaling by Glucocorticoids.Current opinion in endocrine and metabolic research · 2022Article
- Glucocorticoid action in the anterior pituitary gland: Insights from corticotroph physiology.Current opinion in endocrine and metabolic research · 2022Review
- Corticosterone Levels and Glucocorticoid Receptor Gene Expression in High Drinking in the Dark Mice and Their Heterogeneous Stock (HS/NPT) Founder Line.Frontiers in behavioral neuroscience · 2022Article
- The Interface of Nuclear and Membrane Steroid Signaling.Endocrinology · 2021Review
- Is PTSD-Phenotype Associated with HPA-Axis Sensitivity?: The Endocannabinoid System in Modulating Stress Response in Rats.International journal of molecular sciences · 2021Article
- Mifepristone Decreases Chronic Voluntary Ethanol Consumption in Rhesus Macaques.The Journal of pharmacology and experimental therapeutics · 2020Article
- Brain mechanisms of HPA axis regulation: neurocircuitry and feedback in context Richard Kvetnansky lecture.Stress (Amsterdam, Netherlands) · 2020Review
- Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation.Molecular brain · 2019Article
- Sex differences in the hypothalamic-pituitary-adrenal axis: An obstacle to antidepressant drug development?British journal of pharmacology · 2019Review
- Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-DefectiveInternational journal of molecular sciences · 2019Article
- Cell signaling dependence of rapid glucocorticoid-induced endocannabinoid synthesis in hypothalamic neuroendocrine cells.Neurobiology of stress · 2019Article
- Contribution of Non-canonical Cortisol Actions in the Early Modulation of Glucose Metabolism of Gilthead Sea Bream (Frontiers in endocrinology · 2019Article
- Sex-specific deficits in biochemical but not behavioral responses to delay fear conditioning in prenatal alcohol exposure mice.Neurobiology of learning and memory · 2018Article
- Interactive effects of prenatal alcohol exposure and chronic stress in adulthood on anxiety-like behavior and central stress-related receptor mRNA expression: Sex- and time-dependent effects.Psychoneuroendocrinology · 2018Article
- Mineralocorticoid Antagonist Improves Glucocorticoid Receptor Signaling and Dexamethasone Analgesia in an Animal Model of Low Back Pain.Frontiers in cellular neuroscience · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Glucocorticoid binding to the intracellular glucocorticoid receptor (GR) stimulates the translocation of the GR from the cytosol to the nucleus, which leads to the transactivation or transrepression of gene transcription. However, multiple lines of evidence suggest that glucocorticoid signaling can also be initiated from the plasma membrane. Here, we provide evidence for membrane-initiated glucocorticoid signaling by a membrane-impermeant dexamethasone-bovine serum albumin (Dex-BSA) conjugate, which induced GR nuclear trafficking in hypothalamic neurons in vitro and in vivo. The GR nuclear translocation induced by a membrane-impermeant glucocorticoid suggests trafficking of an unliganded GR. The membrane-initiated GR trafficking was not blocked by inhibiting ERK MAPK, p38 MAPK, PKA, Akt, Src kinase, or calcium signaling, but was inhibited by Akt activation. Short-term exposure of hypothalamic neurons to dexamethasone (Dex) activated the glucocorticoid response element (GRE), suggesting transcriptional transactivation, whereas exposure to the Dex-BSA conjugate failed to activate the GRE, suggesting differential transcriptional activity of the liganded compared to the unliganded GR. Microarray analysis revealed divergent transcriptional regulation by Dex-BSA compared to Dex. Together, our data suggest that signaling from a putative membrane glucocorticoid receptor induces the trafficking of unliganded GR to the nucleus, which elicits a pattern of gene transcription that differs from that of the liganded receptor. The differential transcriptional signaling by liganded and unliganded receptors may contribute to the broad range of genetic regulation by glucocorticoids, and may help explain some of the different off-target actions of glucocorticoid drugs.
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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.