Corticotropin-releasing hormone regulates common target genes with divergent functions in corticotrope and neuronal cells

As a key regulator of the neuroendocrine stress axis and as a neuromodulator in the brain, the neuropeptide corticotropin-releasing hormone (CRH) plays an important role in various diseases of the central nervous system. Its cognate receptor CRH receptor type 1 (CRHR1) is a potential novel target for the therapeutic intervention in major depressive disorder. Therefore, a more precise understanding of involved intracellular signaling mechanisms is essential. The objective of this project was to identify specific target genes of CRHR1-mediated signaling pathways in the corticotrope cell line AtT-20 and in the neuronal cell line HN9 using microarray technology and qRT-PCR, respectively. In addition, we assessed the capacity of validated target genes to directly impact on CRHR1-dependent signaling using reporter assays. Thereby, we identified a set of CRHR1 downstream targets with diverging and cell type-specific roles which strengthen the role of CRH and CRHR1 as dynamic modulators of a variety of signal transduction mechanisms and cellular processes.

► CRHR1 signaling affects common target genes in corticotrope and neuronal cells. ► CRHR1 signaling also affects specific target genes as a function of cellular context. ► CRHR1 target genes suggest a crosstalk with other signal transduction pathways. ► Genes regulated by CRH directly modulate CRHR1-dependent signal transduction.