Frog chromogranin A messenger ribonucleic acid encodes three highly conserved peptides. Coordinate regulation of proopiomelanocortin and chromograninA gene expression in the pars intermedia of the pituitary during background color adaptation

Chromogranin A (CgA) is a neuroendocrine secretory protein that is widely u sed as a marker for endocrine neoplasms but whose function is not completel y understood. In mammals, it is thought that CgA is a precursor for biologi cally active peptides. Here, we describe the cloning of a complementary DNA encoding CgA from a nonmammalian vertebrate, the frog Rana ridibunda. Sequ ence analysis revealed that frog CgA. exhibits only 40-44% amino acid seque nce similarity with its mammalian homologues. The amino acid identity is co nfined to three regions (70-80% identity) of the protein that are flanked b y conserved pairs of basic amino acid residues, suggesting that proteolytic processing at these cleavage sites may give rise to three biologically act ive peptides whose sequences have been highly preserved during evolution. T issue distribution analysis by Northern blot and in situ hybridization reve aled the widespread expression of frog CgA messenger RNA in the brain and i n endocrine tissues, the highest concentration occurring in the distal lobe of the pituitary. Adaptation of frog skin color to a dark background cause d a concomitant increase in CgA and POMC messenger RNA levels in the interm ediate lobe of the pituitary. Taken together, these data indicate that CgA may function as a precursor to three highly conserved peptides that may exe rt regulatory functions in the neuroendocrine system.