Relationships among endocrine and signaling-related responses to antidepressants in human monocytic U-937 blood cells: analysis of factors and response patterns.
OBJECTIVE
Antidepressants (AD) (desipramine, imipramine, maprotiline, mirtazapine) and corticosteroid (CS) were examined for their effects on gene expression in human monocytic U-937 blood cells. Endocrine and signaling-related response patterns were determined by expression analysis of different factors, comprising endocrine (glucocorticoid receptor [GR], GR-alpha/beta/gamma; mineralocorticoid receptor [MR]) and signaling-related pathways (p105, STAT3, c-jun, c-fos, JNK1, GAPDH, TNF-alpha).


METHODS
A semiquantitative RT-PCR for factor responses after 24 h of treatment was conducted and exploratory multivariate statistical procedures were applied for further analysis.


RESULTS
Compared to controls, significant reduction of mRNA levels of GR-beta under imipramine and of c-jun under desipramine treatment were found. CS treatment significantly reduced mRNA levels of GR-alpha/beta, TNF-alpha, p105 and c-jun compared to controls. Compared to CS treatment, significantly increased mRNA levels were found for JNK1 under imipramine treatment and for GR-alpha after treatment with all AD examined.


CONCLUSIONS
The multivariate approach meets the requirements of the complex situation of metabolic reactions induced by AD or CS treatment. Our data show that AD affect both, endocrine and signaling-related factors in human monocytic U-937 blood cells, although clearly not in a uniform manner. Hereby, GR is obviously playing a comparably central role. Overall, AD treatment might indeed normalize deviations of cellular endocrine and signaling-related pathways in major depressive disorder via the mechanisms examined.
Gebhardt
Stefan
S
Department of Psychiatry and Psychotherapy, Philipps-University of Marburg, Rudolf-Bultmann-Strasse 8, D-35033 Marburg, Germany. Stefan.Gebhardt@med.uni-marburg.de
Heiser
Philip
P
Fischer
Sabine
S
Schneyer
Thomas
T
Krieg
Jürgen-Christian
JC
Vedder
Helmut
H
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007952:Leukemia, Plasma Cell / Q000188:drug therapy*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000305:Adrenal Cortex Hormones; D000928:Antidepressive Agents; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C121943:glucocorticoid receptor beta