Transcriptional regulation of the bovine CYP17 gene: Two nuclear orphan receptors determine activity of cAMP-responsive sequence 2

The CYP17 gene contains in its promoter region at least two cis-acting elements (cAMP-responsive sequence 1 and 2, CRS1 and CRS2) that are necessary for adrenocorticotropin (ACTH) induced transcription. The CRS2 element contains a 6 bp repeat similar to binding sites for members of the nuclear hormone receptor superfamily of transcription factors. We present data that establish the repeated part of CRS2 (repCRS2) as a target of two nuclear orphan receptors; steroidogenic factor 1 (SF-1) and chicken ovalbumin upstream promoter transcription factor (COUP-TF). The repCRS2 element was found to form COUP-TF-related complexes with nuclear extracts from all cell lines tested, whereas SF-1-related complexes were only formed with extracts from steroidogenic Y1 cells. Transfection studies of steroidogenic cells demonstrated that SF-1 acts as an activator of repCRS2-dependent transcription of reporter genes.