Structural organization of the corticotropin-beta-lipotropin precursor gene

The human and the bovine corticotropin (ACTH)-beta-lipotropin (LPH) precursor gene have been isolated and characterized. Both genes consist of three exons which are divided by two large introns at exactly the same positions. One of the introns is inserted within the segment transcribed into the 5'-untranslated region of the mRNA, and the other interrupts the protein-coding sequence near the signal peptide region. The largest exon encodes most of the protein sequence which includes the three repeated melanotropin (MSH) peptides and other biologically active peptides such as ACTH and beta-endorphin. Thus, there is no apparent correspondence between the repetitive structure of the precursor protein and the structural organization of its gene. Comparison of the nucleotide sequences of the human and the bovine gene reveals that three regions are highly conserved, i.e., the region extending from the signal peptide to gamma-MSH, the ACTH region and the beta-MSH/beta-endorphin region. This suggests that the peptide(s) in the amino-terminal region, including gamma-MSH, may be of physiological importance, as is the case for ACTH and beta-endorphin. The different biologically active component peptides of the ACTH-beta-LPH precursor, encoded by a single gene, seem to be involved in the defense mechanism of the living organism by acting coordinately in the central nervous system as well as in peripheral tissues. The identification of the mRNA encoding the ACTH-beta-LPH precursor in a human ectopic ACTH-producing tumor is also reported.