The corticotropin-releasing hormone (CRH), its related peptides (urocortins) and receptors (CRHR1 and CRHR2) orchestrate the response and adaptation to stress, acting on the hypothalamic-pituitary-adrenal axis and in various brain regions. Dysregulation of the CRH system is causally linked to psychiatric disorders such as anxiety and depression. Our previous results suggest that the signaling pathways activated by ligand stimulation of CRHR2 depend on the cellular context. Taking this into consideration we propose to extend the knowledge of the CRHR2 and urocortins using transgenic mice to explore signaling and trafficking in a relevant physiological context.