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Modulation of the human glucocorticoid receptor function by antidepressive compounds
Miho Okuyama-Tamura1, Masahiko Mikuni, Itaru Kojima
1Department of Psychiatry, Gunma University School of Medicine, Maebashi, Japan.
Neuroscience Letters
|May 22, 2003
Summary
Certain antidepressants rapidly move the glucocorticoid receptor (GR) into the cell nucleus and inhibit its function. This suggests a novel mechanism for how antidepressants may combat depression by affecting the stress hormone system.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity is linked to depression.
- The glucocorticoid receptor (GR) plays a key role in regulating the HPA axis.
Purpose of the Study:
- To investigate the in vitro effects of various antidepressant agents on glucocorticoid receptor (GR) function.
- To determine if antidepressants influence GR translocation and transcriptional activity.
Main Methods:
- Human lymphocytes were treated with different classes of drugs.
- Glucocorticoid receptor (GR) translocation to the nucleus was assessed.
- Dexamethasone-induced GR-mediated transcription was measured in the presence of antidepressants.
Main Results:
- Antidepressants (desipramine, clomiplamine, fluoxetine, milnacipran, clorgyline) induced rapid and sustained GR nuclear translocation in lymphocytes.
- Tranquilizers, lithium, and verapamil did not affect GR translocation.
- Antidepressants inhibited dexamethasone-induced GR-mediated transcription without affecting it independently.
Conclusions:
- Structurally diverse antidepressants can modulate glucocorticoid receptor (GR) function.
- Antidepressant-induced GR translocation and inhibition of GR-mediated transcription represent a potential mechanism of action in depression treatment.