Stress‐induced changes in gene expression of urocortin 2 and other CRH peptides in rat adrenal medulla: involvement of glucocorticoids

The corticotropin‐releasing hormone (CRH) family regulates the endocrine stress response. Here, we examined the effect of immobilization stress (IMO) on gene expression of adrenomedullary CRH family members. Urocortin 2 (Ucn2) has the highest basal gene expression and is increased by > 30‐fold in response to single IMO and about 10‐fold after six daily repeated IMO. IMO also induced a smaller rise in CRH (six‐fold) and CRH receptor type 1 (CRHR1; two‐fold with single IMO). The influence of glucocorticoids was examined. Dexamethasone (DEX) or corticosterone greatly increased Ucn2 mRNA levels in PC12 cells in a dose‐dependent manner. The DEX elicited rise in Ucn2 was abolished by actinomycin D pre‐treatment, indicating a transcriptionally mediated response. DEX also triggered a rise in CRHR1 and lowered CRH mRNA levels. In CRH‐knockout mice, where the IMO‐induced rise in corticosterone was attenuated, the response of IMO on Ucn2, as well as CRHR2 mRNAs was absent. Overall, the results suggest that the stress‐triggered rise in glucocorticoids is involved in the large induction of Ucn2 mRNA levels by IMO, which may allow Ucn2 to act in an autocrine/paracrine fashion to modulate adrenomedullary function, or act as an endocrine hormone. We found that gene expression of urocortin 2 (Ucn2) is not only the most abundant of CRH family members in adrenal medulla but also that stress triggers an enormous induction of Ucn2 mRNA levels. The stress‐triggered release of CRH and rise of glucocorticoids is important for Ucn2 gene expression. Elevated Ucn2 can modulate adrenomedullary function in autocrine/paracrine fashion, with possible endocrine effect.