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.
Zanger
U M
UM
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
Kagawa
N
N
Lund
J
J
Waterman
M R
MR
D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D000242:Cyclic AMP / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D014158:Transcription, Genetic
D009687:Nuclear Proteins; D000242:Cyclic AMP; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase