Indeed, CREB-mediated transcription of StAR is increased by the activation of orphan nuclear receptor transcription factors steroidogenic factor-1 (SF-1) (13, 14) and Nur77 (15), encoded by the NR5A1 and NR4A1 genes, respectively, and negatively regulated by the atypical orphan nuclear receptor transcription factor DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenital critical region on X-chromosome, gene 1, encoded by the NR0B1 gene) (16). This evidence concerns the gene NR4A1 and chronic primary adrenal insufficiency.