Do Glycine-Extended Hormone Precursors have Clinical Significance?

Abstract

Half of the known peptide hormones are C-terminally amidated. Subsequent biogenesis studies have shown that the immediate precursor is a glycine-extended peptide. The clinical interest in glycine-extended hormones began in 1994, when it was suggested that glycine-extended gastrin stimulated cancer cell growth. Accompanying findings of gastrin gene expression in common cancers spurred the interest. The interest is now accompanied by skepticism, which is due to failure to demonstrate truly specific receptors for glycine-extended peptides and failure to demonstrate separate physiological and clinical effects of glycine-extended precursors for most other amidated hormones than gastrin and cholecystokinin (CCK). The idea of glycine-extended peptides as independent messengers was interesting. But clinical science has to move ahead from ideas that cannot be supported at key points after decades of research.

Keywords:

• binding proteins
• bioactive peptides
• carboxyamidation
• carcinogenesis
• glycine-extended peptides
• growth promotion
• peptide biosynthesis
• peptide hormones
• progastrins
• receptors

Acknowledgements

The skilful secretarial assistance of C Bundgaard is gratefully acknowledged.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.