Distinct biochemical mechanisms for cAMP-dependent transcription of CYP17 and CYP21

Optimal steroidogenic capacity in the adrenal cortex is regulated by ACTH via cAMP and involves transcription of the genes encoding the adrenocortical steroid hydroxylases. The microsomal steroid hydroxylases, P45017 alpha and P450C21, are encoded by CYP17 and CYP21, respectively. These genes are thought to have arisen from a common progenitor gene and are coordinately regulated by ACTH. The cAMP responsive sequences (CRS) located in the 5'-flanking regions of these genes are distinct from one another and from known consensus sequences imparting cAMP responsiveness in other genes. The CYP21 CRS binds a putative adrenal-specific nuclear protein. In contrast, the CYP17 CRSI binds a ubiquitous protein that is apparently active only in steroidogenic cells. Thus the ACTH-dependent transcription of these two genes, which have a common evolutionary origin and are coordinately expressed in the adrenal cortex, involves distinct biochemical mechanisms.