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.