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Endocrinology Vol. 140, No. 9 4104-4112
Copyright © 1999 by The Endocrine Society


ARTICLES

Frog Chromogranin A Messenger Ribonucleic Acid Encodes Three Highly Conserved Peptides. Coordinate Regulation of Proopiomelanocortin and Chromogranin A Gene Expression in the Pars Intermedia of the Pituitary During Background Color Adaptation1

Valérie Turquier2, Hubert Vaudry, Sylvie Jégou and Youssef Anouar

European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, Institut National de la Santé et de la Recherche Médicale (INSERM U413), Centre National de la Recherche Scientifique (UA CNRS), University of Rouen, 76821 Mont-Saint-Aignan, France

Address all correspondence and requests for reprints to: Dr. H. Vaudry, European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U-413, UA CNRS, University of Rouen, 76821 Mont-Saint-Aignan, France. E-mail: hubert.vaudry{at}univ-rouen.fr

Chromogranin A (CgA) is a neuroendocrine secretory protein that is widely used as a marker for endocrine neoplasms but whose function is not completely understood. In mammals, it is thought that CgA is a precursor for biologically active peptides. Here, we describe the cloning of a complementary DNA encoding CgA from a nonmammalian vertebrate, the frog Rana ridibunda. Sequence analysis revealed that frog CgA exhibits only 40–44% amino acid sequence similarity with its mammalian homologues. The amino acid identity is confined to three regions (70–80% identity) of the protein that are flanked by conserved pairs of basic amino acid residues, suggesting that proteolytic processing at these cleavage sites may give rise to three biologically active peptides whose sequences have been highly preserved during evolution. Tissue distribution analysis by Northern blot and in situ hybridization revealed the widespread expression of frog CgA messenger RNA in the brain and in endocrine tissues, the highest concentration occurring in the distal lobe of the pituitary. Adaptation of frog skin color to a dark background caused a concomitant increase in CgA and POMC messenger RNA levels in the intermediate lobe of the pituitary. Taken together, these data indicate that CgA may function as a precursor to three highly conserved peptides that may exert regulatory functions in the neuroendocrine system.




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