PMID- 10404468
OWN - NLM
STAT- MEDLINE
DCOM- 19991227
LR  - 20190921
IS  - 0022-3956 (Print)
IS  - 0022-3956 (Linking)
VI  - 33
IP  - 4
DP  - 1999 Jul-Aug
TI  - Regulation of glucocorticoid receptor-mRNA in human blood cells by amitriptyline 
      and dexamethasone.
PG  - 303-8
AB  - 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.
FAU - Vedder, H
AU  - Vedder H
AD  - Department of Psychiatry and Psychotherapy, Philipps-University of Marburg, 
      Germany. vedder@mailer.uni-marburg.de
FAU - Bening-Abu-Shach, U
AU  - Bening-Abu-Shach U
FAU - Lanquillon, S
AU  - Lanquillon S
FAU - Krieg, J C
AU  - Krieg JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Glucocorticoids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 1806D8D52K (Amitriptyline)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
SB  - IM
MH  - Adult
MH  - Amitriptyline/*pharmacology
MH  - Antidepressive Agents, Tricyclic/*pharmacology
MH  - Dexamethasone/*pharmacology
MH  - Gene Expression Regulation, Developmental
MH  - Glucocorticoids/*pharmacology
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/genetics
MH  - Humans
MH  - Hypothalamo-Hypophyseal System/drug effects
MH  - Male
MH  - Pituitary-Adrenal System/drug effects
MH  - RNA, Messenger/*genetics/*metabolism
MH  - *Receptors, Glucocorticoid/blood/drug effects/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription, Genetic/genetics
MH  - Up-Regulation/*physiology
EDAT- 1999/07/15 00:00
MHDA- 1999/07/15 00:01
CRDT- 1999/07/15 00:00
PHST- 1999/07/15 00:00 [pubmed]
PHST- 1999/07/15 00:01 [medline]
PHST- 1999/07/15 00:00 [entrez]
AID - S0022-3956(99)00006-0 [pii]
AID - 10.1016/s0022-3956(99)00006-0 [doi]
PST - ppublish
SO  - J Psychiatr Res. 1999 Jul-Aug;33(4):303-8. doi: 10.1016/s0022-3956(99)00006-0.