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Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour

Abstract

The neuroregulation of growth hormone (GH) secretion is mediated in part by a stimulatory, GH-releasing factor (GRF) and an inhibitory peptide, somatostatin1, both of which reach the adenohypophysis by the hypothalamic-hypophysial portal system2. Somatostatin has been shown to be a tetradecapeptide3,4, a large form of which was later also sequenced5. The existence of a GRF is supported by physiological evidence6–9 and by reports of GH-releasing activity in hypothalamic extracts10–17. Although several agents with GH-releasing activity have been identified14–16, none is of high potency and fulfils the criteria expected of a physiological GRF18,19. GH-releasing activity observed in extracts of carcinoid and pancreatic islet tumours removed from patients with GH hypersecretion, acromegaly and pituitary adenoma or hyperplasia has been partially characterized20–23. We report here the sequence of a 40 residue GH-releasing peptide purified from a pancreatic islet tumour described earlier by Thorner et al.23. A synthetic replicate of this peptide, termed human pancreatic tumour GRF [hpGRF(1–40)]-OH, co-elutes on HPLC with the native peptide and is highly potent in stimulating GH secretion in vitro and in vivo. A close structural homology with the peptides of the glucagon–secretin family, and more particularly with PHI24, is recognized. Structure–activity studies show that hpGRF(1–29)-NH2 has full intrinsic activity and potency in vitro.

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Rivier, J., Spiess, J., Thorner, M. et al. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature 300, 276–278 (1982). https://doi.org/10.1038/300276a0

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