Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors

CYP17 gene transcription is activated by SF-1 binding to a cyclic AMP-respo nsive sequence within the promoter region of the gene, and its transcriptio n is inhibited by COUP-TF binding to the sequence. Another orphan receptor, DAX-1, is shown to act as a suppressor of SF-1-mediated transcription We e xamined the expression level of these orphan receptors in adrenocortical tu mors and compared the results with CYP17 expression. CYP17 was highly expre ssed in cortisol-producing adenomas, whereas COUP-TF and DAX-1 expression l evels were very low. In deoxycorticosterone-producing adenomas, on the othe r hand, CYP17 expression was extremely low, whereas DAX-1 was highly expres sed and SF-1 expression was slightly decreased. In conclusion, the reciproc al expression of CYP17 and the transcriptional repressors COUP-TF and DAX-1 indicates that these orphan receptors have a pathophysiologic role in the excessive hormone production in cortisol- and deoxycorticosterone-producing adrenocortical tumors.