Mechanisms for transcriptional activation of rat cyp11b1 gene by adrenocorticotropin

The CYP11B1 gene encodes steroid 11β-hydroxylase P.450, which is responsible for the last step in the biosynthesis of the major glucoeorticoids, conticosterone and cortisol. In tile present study, we found using adrenocortical Y1 cells that binding of AP-1 transcription factors (dimers composed of the Jun and Fos family proteins) to its site in the CYPI1B1 promoter is required for transcriptional activation of the gene by adrenocorticotropin (ACTH) as well as for its basal level transcription. Analyses of mRNAs for the ,lun and Fos family proteins suggested that composition of AP-1 factors changed significantly upon treatment of Y1 cells with ACTtt: c-Jun/c-Fos, JunB/c-Fos are induced temporarily and c-Jun/Fra-2 is induced lastingly, while JunD/Fra-2 is constitutively expressed. Total amounts of AP-I factors in the ceils does no', greatly change before and after tile treatment with ACTtt. These results together with those by cotransfection of expression vectors encoding the ,lun or Fos family proteins with a reporter gene driven by the CYP11B1 promoter into the cells revealed that the AP l factors induced upon ACTtt treatment transactivate tile promoter more strongly than those expressed constitutively. Dibutyryl cAMP, which also activates the CYPIIB1 gene transcription, had similar effects on the composition of AP-1 factors in Y1 cells to those observed with ACTH, suggesting that the transcriptional activation by ACTIt is me diated through a cAMP pathway. Supported by" grants from the Ministry of Education. Science and Culture of Japan and from the Mitsubishi Foundation.