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.
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
Cornelia
C
Graf
Claudia
C
Kuehne
Markus
M
Panhuysen
Benno
B
Puetz
Peter
P
Weber
Florian
F
Holsboer
Wolfgang
W
Wurst
Jan M
JM
Deussing
D000818:Animals; D045744:Cell Line, Tumor; D052680:Corticotrophs / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D020218:Response Elements; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D059467:Transcriptome; D000099052:CRF Receptor, Type 1
D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D049409:Luciferases, Firefly