Differential regulation and roles of urocortins in human adrenal H295R cells.

Three urocortins (Ucns) are known as members of the corticotropin-releasing factor (CRF) family of peptides and serve as natural ligands for CRF receptors. Ucn1 and Ucn3 exhibit potent effects on the adrenal system via the CRF receptors. This study aimed to explore the regulation and roles of Ucns in the adrenal system using human adrenal carcinoma H295R cells, which express Ucn1, Ucn2, Ucn3, CRF receptor type 1 (CRF(1) receptor), and CRF receptor type 2a (CRF(2a) receptor) mRNA. Forskolin, which stimulates adenylate cyclase and then increases intracellular cAMP production, was shown to transiently decrease Ucn1 and Ucn2 mRNA levels, but increase Ucns 1-3 mRNA levels in H295R cells. Steroidogenic acute regulatory protein, Cyp11beta1, and Cyp11beta2 mRNA levels, and both cortisol and aldosterone secretions were elevated by Ucn1. Cell viability was reduced by both Ucn1 and Ucn3 via the CRF(2) receptor in H295R cells. Ucn1 and Ucn3 increased the expression of the cAMP-response element binding protein and extracellular signal-related kinase (ERK) phosphorylations. The ERK and protein kinase A pathways were involved in Ucn3-decreased cell viability.