Differential expression of an orphan receptor COUP-TFI and corepressors in adrenal tumors.

Recently, it has been shown that CYP17 gene transcription is activated by SF-1 (Steroidogenic Factor-1) binding to a cyclic AMP-responsive sequence within the promoter region of the gene, whereas it is inhibited by COUP-TF (Chicken Ovalbumin Upstream Promoter-Transcription Factor) binding to the sequence. We have shown that transcriptional repression by COUP-TFI is mediated by corepressors, N-CoR (nuclear receptor corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone-receptor). Therefore, we compared the expression of COUP-TFI, N-CoR and SMRT in non-hyperfunctioning adrenocortical adenomas and normal adrenal glands. We found significantly higher expression of COUP-TFI mRNA in non-hyperfunctioning adenomas (n=5, 227+/-18%) than in normal adrenals (n=5, 96+/-4%). Interestingly, the pattern of N-CoR and SMRT expression was different compared with COUP-TFI expression. These data suggest that COUP-TFI, N-CoR, and SMRT may play a differential role in steroid biosynthesis of non-hyperfunctioning adenomas.