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.
Discussion: 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.