Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Line, Tumor
-
Clone Cells
-
Corticotropin-Releasing Hormone / metabolism
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Gene Expression Regulation
-
Interleukin-1 / metabolism*
-
Mice
-
Mitogen-Activated Protein Kinases / metabolism
-
Mutation
-
Nuclear Receptor Subfamily 4, Group A, Member 1
-
Pituitary Neoplasms / pathology
-
Pro-Opiomelanocortin / drug effects
-
Pro-Opiomelanocortin / genetics
-
Pro-Opiomelanocortin / metabolism*
-
Promoter Regions, Genetic
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Steroid
-
Response Elements / genetics
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
-
Transcription, Genetic
-
p38 Mitogen-Activated Protein Kinases
Substances
-
DNA-Binding Proteins
-
Interleukin-1
-
Nr4a1 protein, mouse
-
Nuclear Receptor Subfamily 4, Group A, Member 1
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Steroid
-
Transcription Factors
-
Pro-Opiomelanocortin
-
Corticotropin-Releasing Hormone
-
Mitogen-Activated Protein Kinases
-
p38 Mitogen-Activated Protein Kinases