Nur77 induction and activation are necessary for interleukin‐1 stimulation of proopiomelanocortin in AtT‐20 corticotrophs

Nur77 and Nurr1 are critical for proopiomelanocortin (POMC) regulation by corticotrophin releasing hormone (CRH) in corticotrophs. We analyze the regulation and activity of Nur77 by interleukin (IL)-1 in AtT-20 corticotrophic cells and its consequences on POMC regulation. IL-1 induces Nur77 and not Nurr1 mRNA and shows an increased transcriptional activity on the NurRE site, an effect dependent of p38 protein kinase activity. A NurRE mutation abrogates POMC promoter transcription by IL-1 and a stable AtT-20 clone overexpressing a dominant negative form of Nur77 is unresponsive to IL-1-dependent POMC induction and adrenocorticotrophin (ACTH) secretion. These results demonstrate that Nur77 is essential for POMC stimulation by IL-1 in corticotrophs.