Regulation of glucocorticoid receptor-mRNA in human blood cells by amitriptyline and dexamethasone.
Recent research suggests that antidepressants exert their clinical action in depression via the restoration of glucocorticoid receptor (GR) function with a subsequent normalization of the altered feed-back regulation of the hypothalamic-pituitary adrenocortical (HPA) system. We, therefore, studied the effects of amitriptyline, a standard antidepressant, and of the glucocorticoid dexamethasone, which has recently been reported to possess antidepressive properties, on glucocorticoid receptor mRNA (GR-mRNA) derived from blood cells of healthy male volunteers. Whole blood samples were exposed in vitro for 24 h to amitriptyline and dexamethasone, the mRNA was extracted, transcripts of the 'house-keeping gene' glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the GR-gene were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) and semiquantitatively determined by subsequent densitometry. In a concentration of 10 nM, amitriptyline induced a significant increase in GR-mRNA (GR/GAPDH ratio) to 186 +/- 31% of the control condition, while a concentration of 10 microM of amitriptyline resulted in an increase of GR-mRNA (GR/GAPDH ratio) to 165 +/- 36%. Dexamethasone also up-regulated blood cell GR-mRNA (GR/GAPDH ratio) levels at a concentration of 10 nM to 184 +/- 29%, whereas an incubation with 10 microM apparently resulted in toxic effects on blood cells with a decreased amount of total mRNA samples recovered. In conclusion, we here show an increase of GR-mRNA in human blood cells after treatment with amitriptyline and dexamethasone, pointing to a direct action of these substances on GR-gene expression in a human system.
Department of Psychiatry and Psychotherapy, Philipps-University of Marburg, Germany. vedder@mailer.uni-marburg.de
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D000328:Adult; D000639:Amitriptyline / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000097:blood / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology*
D000929:Antidepressive Agents, Tricyclic; D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D000639:Amitriptyline; D003907:Dexamethasone; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases