Modulation of the human glucocorticoid receptor function by antidepressive compounds.
Hyperactivity of the hypothalamic-pituitary-adrenal axis is associated with depression. We investigated the effect of various types of antidepressant agents in vitro on the function of glucocorticoid receptor (GR). Desipramine, clomiplamine, fluoxetine, milnacipran and clorgyline all induced rapid and sustained translocation of GR into the nucleus of human lymphocytes. In contrast, major and minor tranquilizers, lithium and verapamil, a blocker of membrane steroid transporter, were without effect. These antidepressants did not affect GR-mediated transcription by themselves, but significantly inhibited dexamethasone-induced transcription. These results indicate that structurally different antidepressants induce translocation of GR and inhibit GR-mediated transcription.
Okuyama-Tamura
Miho
M
Department of Psychiatry, Gunma University School of Medicine, Maebashi, Japan.
Mikuni
Masahiko
M
Kojima
Itaru
I
D000818:Animals; D000928:Antidepressive Agents / Q000145:classification / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D019556:COS Cells / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008094:Lithium / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D014149:Tranquilizing Agents / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection / Q000379:methods; D014178:Translocation, Genetic / Q000187:drug effects
D000928:Antidepressive Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014149:Tranquilizing Agents; D003907:Dexamethasone; D008094:Lithium