Cortisol Rapidly Facilitates Glucocorticoid Receptor Translocation to the Plasma Membrane in Primary Trout Hepatocytes
Bibliographic record
Abstract
Glucocorticoids (GCs) stimulate rapid cell signalling by activating the membrane-anchored intracellular glucocorticoid receptor (GR). However, the recruitment of the GR to the plasma membrane to facilitate nongenomic signalling is far from clear. As cytosolic free calcium ([Ca2+]i) is involved in intracellular protein dynamics, we tested the hypothesis that acute elevation in cortisol levels rapidly stimulates GR translocation to the plasma membrane via a calcium-dependent process in rainbow trout (Oncorhynchus mykiss) hepatocytes. To test this, we monitored temporal changes in intracellular GR distribution in response to cortisol exposure. Immunofluorescence labelling showed that the GR was present in cytosolic and nuclear compartments in trout hepatocytes. However, upon cortisol exposure, the GR rapidly (within 5 min) formed punctate and colocalized with caveolin-1, suggesting plasma membrane localization of the receptor. This redistribution of the GR to the plasma membrane was transient and lasted for 30 min and was evident even upon exposure to cortisol-BSA, a membrane-impermeable analogue of the steroid. The rapid cortisol-mediated GR translocation to the plasma membrane involved F-actin polymerization and was completely abolished in the presence of either EGTA or Cpd5J-4, a calcium release–activated calcium (CRAC) channel blocker. Additionally, the modulation of the biophysical properties of the plasma membrane by cholesterol or methyl β-cyclodextrin, which led to changes in ([Ca2+]i) levels, modified GR translocation to the plasma membrane. Altogether, acute cortisol-mediated rise in ([Ca2+]i) levels rapidly stimulated the translocation of intracellular GR to the plasma membrane, and we propose this as a mechanism promoting the nongenomic action of the GR for hepatocyte stress resistance.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".